WorldWideScience

Sample records for actinohivin blocks hiv

  1. Lectins with Anti-HIV Activity: A Review

    Directory of Open Access Journals (Sweden)

    Ouafae Akkouh

    2015-01-01

    Full Text Available Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin lectin, concanavalin A, Galanthus nivalis (snowdrop agglutinin-related lectins, Musa acuminata (banana lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus. The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.

  2. HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis

    Science.gov (United States)

    2018-01-01

    ABSTRACT Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments. IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the

  3. Curaxin CBL0100 Blocks HIV-1 Replication and Reactivation through Inhibition of Viral Transcriptional Elongation

    Directory of Open Access Journals (Sweden)

    Maxime J. Jean

    2017-10-01

    Full Text Available Despite combination antiretroviral therapy (cART, acquired immunodeficiency syndrome (AIDS, predominantly caused by the human immunodeficiency virus type 1 (HIV-1, remains incurable. The barrier to a cure lies in the virus' ability to establish a latent infection in HIV/AIDS patients. Unsurprisingly, efforts for a sterilizing cure have focused on the “shock and kill” strategy using latency-reversing agents (LRAs to complement cART in order to eliminate these latent reservoirs. However, this method faces numerous challenges. Recently, the “block and lock” strategy has been proposed. It aims to reinforce a deep state of latency and prevent sporadic reactivation (“blip” of HIV-1 using latency-promoting agents (LPAs for a functional cure. Our studies of curaxin 100 (CBL0100, a small-molecule targeting the facilitates chromatin transcription (FACT complex, show that it blocks both HIV-1 replication and reactivation in in vitro and ex vivo models of HIV-1. Mechanistic investigation elucidated that CBL0100 preferentially targets HIV-1 transcriptional elongation and decreases the occupancy of RNA Polymerase II (Pol II and FACT at the HIV-1 promoter region. In conclusion, CBL0100 is a newly identified inhibitor of HIV-1 transcription that can be used as an LPA in the “block and lock” cure strategy.

  4. Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs.

    Science.gov (United States)

    Cheng, Liang; Ma, Jianping; Li, Jingyun; Li, Dan; Li, Guangming; Li, Feng; Zhang, Qing; Yu, Haisheng; Yasui, Fumihiko; Ye, Chaobaihui; Tsao, Li-Chung; Hu, Zhiyuan; Su, Lishan; Zhang, Liguo

    2017-01-03

    Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-α/β receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1-infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1-induced immune hyperactivation and rescued anti-HIV-1 immune responses in T cells from HIV-1-infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1-infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1-associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART.

  5. Inhibition of Non Canonical HIV-1 Tat Secretion Through the Cellular Na+,K+-ATPase Blocks HIV-1 Infection

    Directory of Open Access Journals (Sweden)

    Silvia Agostini

    2017-07-01

    Full Text Available Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na+,K+-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity. Treatment of CD4+ T-cells with short peptides corresponding to the Tat-binding regions of the pump alpha subunit impaired extracellular Tat release and blocked HIV-1 replication. Thus, non canonical, extracellular Tat secretion is essential for viral infectivity.

  6. Candidate Microbicides Block HIV-1 Infection of Human Immature Langerhans Cells within Epithelial Tissue Explants

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Cohen, Sandra S.; Borris, Debra L.; Aquilino, Elisabeth A.; Glushakova, Svetlana; Margolis, Leonid B.; Orenstein, Jan M.; Offord, Robin E.; Neurath, A. Robert; Blauvelt, Andrew

    2000-01-01

    Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1Ba-L infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08–4.77%). HIV-1–infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1–1 μg HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1Ba-L (an R5 HIV-1 strain) more efficiently infected LC–T cell cocultures when compared with HIV-1IIIB (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testing of agents designed to block sexual transmission of HIV-1. PMID:11085750

  7. P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

    Science.gov (United States)

    Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

    2015-09-01

    HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF

  8. BI-2 destabilizes HIV-1 cores during infection and Prevents Binding of CPSF6 to the HIV-1 Capsid.

    Science.gov (United States)

    Fricke, Thomas; Buffone, Cindy; Opp, Silvana; Valle-Casuso, Jose; Diaz-Griffero, Felipe

    2014-12-11

    The recently discovered small-molecule BI-2 potently blocks HIV-1 infection. BI-2 binds to the N-terminal domain of HIV-1 capsid. BI-2 utilizes the same capsid pocket used by the small molecule PF74. Although both drugs bind to the same pocket, it has been proposed that BI-2 uses a different mechanism to block HIV-1 infection when compared to PF74. This work demonstrates that BI-2 destabilizes the HIV-1 core during infection, and prevents the binding of the cellular factor CPSF6 to the HIV-1 core. Overall this short-form paper suggests that BI-2 is using a similar mechanism to the one used by PF74 to block HIV-1 infection.

  9. Deletions in the fifth alpha helix of HIV-1 matrix block virus release

    International Nuclear Information System (INIS)

    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J.; Chen, Han; Zhou, You; Belshan, Michael

    2014-01-01

    The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1–α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release

  10. Deletions in the fifth alpha helix of HIV-1 matrix block virus release

    Energy Technology Data Exchange (ETDEWEB)

    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Chen, Han [Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE (United States); Zhou, You [Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE (United States); Nebraska Center for Virology, Lincoln, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Nebraska Center for Virology, Lincoln, NE (United States)

    2014-11-15

    The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1–α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release.

  11. Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells.

    Science.gov (United States)

    Baldauf, Hanna-Mari; Stegmann, Lena; Schwarz, Sarah-Marie; Ambiel, Ina; Trotard, Maud; Martin, Margarethe; Burggraf, Manja; Lenzi, Gina M; Lejk, Helena; Pan, Xiaoyu; Fregoso, Oliver I; Lim, Efrem S; Abraham, Libin; Nguyen, Laura A; Rutsch, Frank; König, Renate; Kim, Baek; Emerman, Michael; Fackler, Oliver T; Keppler, Oliver T

    2017-03-07

    Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis. We find that virion-packaged Vpx proteins from a second SIV lineage, SIV of red-capped mangabeys or mandrills (SIVrcm/mnd-2), increased HIV infection in resting CD4 T cells, but not in macrophages, and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in SAMHD1 phosphorylation. Vpx rcm/mnd-2 virion incorporation resulted in a dramatic increase of HIV-1 RT intermediates and viral cDNA in infected resting CD4 T cells. These analyses also revealed a barrier limiting HIV-1 infection of resting CD4 T cells at the level of nuclear import. Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early postentry steps in a Vpx rcm/mnd-2-like fashion. Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with Aicardi-Goutières syndrome. These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of RT that acts independently of dNTP concentrations and is specific to resting CD4 T cells.

  12. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    International Nuclear Information System (INIS)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

    2014-01-01

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs

  13. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  14. Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes.

    Science.gov (United States)

    Setz, Christian; Friedrich, Melanie; Rauch, Pia; Fraedrich, Kirsten; Matthaei, Alina; Traxdorf, Maximilian; Schubert, Ulrich

    2017-08-12

    In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity. Furthermore, the replication capacity of X4- and R5-tropic HIV-1 NL4-3 in human lymphatic tissue is decreased upon treatment with these inhibitors without affecting cell viability. Most strikingly, combinatory treatment with DIs and proteasome inhibitors synergistically blocks virus replication at concentrations where mono-treatment was ineffective, indicating that DIs can boost the therapeutic effect of proteasome inhibitors. In addition, P22077 and PR-619 increase the polyubiquitination of Gag and thus its entry into the UPS and the major histocompatibility complex (MHC)-I pathway. In summary, our data point towards a model in which specific inhibitors of DUBs not only interfere with virus spread but also increase the immune recognition of HIV-1 expressing cells.

  15. Blocking the benefit of group-based HIV-prevention efforts during adolescence: the problem of HIV-related stigma.

    Science.gov (United States)

    Barker, David H; Swenson, Rebecca R; Brown, Larry K; Stanton, Bonita F; Vanable, Peter A; Carey, Michael P; Valois, Robert F; Diclemente, Ralph J; Salazar, Laura F; Romer, Daniel

    2012-04-01

    HIV-related stigma has been shown to impede HIV-antibody testing and safer sexual practices in adults. Less is known about its effects on prevention programs among at-risk youth. This study examined the longitudinal relationships between HIV-stigma and HIV-knowledge following completion of a validated group-based intervention. Data were provided by 1,654 African-American adolescents who participated in a large multi-city prevention trial (Project iMPACCS). Participants were randomly assigned to an empirically-validated skill-based intervention or a general health promotion control group. Both stigma and knowledge were assessed at baseline and post-intervention. Results suggested that adolescents participating in the intervention showed improvements in knowledge and decreases in stigma when compared to controls. Improvements in stigma appeared to be partly driven by improvements in knowledge. Higher baseline stigma was shown to reduce gains in knowledge in both the treatment and control groups. Results suggest that HIV-stigma can interfere with how youth identify with and internalize messages from group-based prevention trials.

  16. Synthetic AAV/CRISPR vectors for blocking HIV-1 expression in persistently infected astrocytes.

    Science.gov (United States)

    Kunze, Christine; Börner, Kathleen; Kienle, Eike; Orschmann, Tanja; Rusha, Ejona; Schneider, Martha; Radivojkov-Blagojevic, Milena; Drukker, Micha; Desbordes, Sabrina; Grimm, Dirk; Brack-Werner, Ruth

    2018-02-01

    Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes. Analysis of AAV9P1 transduction efficiencies with single brain cell populations, including primary human brain cells, as well as human brain organoids demonstrated that AAV9P1 targeted terminally differentiated human astrocytes much more efficiently than neurons. We then investigated whether AAV9P1 can be used to deliver HIV-inhibitory genes to astrocytes. To this end we generated AAV9P1 vectors containing genes for HIV-1 proviral editing by CRISPR/Cas9. Latently HIV-1 infected astrocytes transduced with these vectors showed significantly diminished reactivation of proviruses, compared with untransduced cultures. Sequence analysis identified mutations/deletions in key HIV-1 transcriptional control regions. We conclude that AAV9P1 is a promising tool for gene delivery to astrocytes and may facilitate inactivation/destruction of persisting HIV-1 proviruses in astrocyte reservoirs. © 2017 Wiley Periodicals, Inc.

  17. Natural Plant Alkaloid (Emetine Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity

    Directory of Open Access Journals (Sweden)

    Ana Luiza Chaves Valadão

    2015-06-01

    Full Text Available Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine’s potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V. Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine.

  18. μ-opioid modulation of HIV-1 coreceptor expressionand HIV-1 replication

    International Nuclear Information System (INIS)

    Steele, Amber D.; Henderson, Earl E.; Rogers, Thomas J.

    2003-01-01

    A substantial proportion of HIV-1-infected individuals are intravenous drug users (IVDUs) who abuse opiates. Opioids induce a number of immunomodulatory effects that may directly influence HIV-1 disease progression. In the present report, we have investigated the effect of opioids on the expression of the major HIV-1 coreceptors CXCR4 and CCR5. For these studies we have focused on opiates which are ligands for the μ-opioid receptor. Our results show that DAMGO, a selective μ-opioid agonist, increases CXCR4 and CCR5 expression in both CD3 + lymphoblasts and CD14 + monocytes three- to fivefold. Furthermore, DAMGO-induced elevation of HIV-1 coreceptor expression translates into enhanced replication of both X4 and R5 viral strains of HIV-1. We have confirmed the role of the μ-opioid receptor based on the ability of a μ-opioid receptor-selective antagonist to block the effects of DAMGO. We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection. We suggest that the capacity of μ-opioids to increase HIV-1 coreceptor expression and replication may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression

  19. Heterophilic interference in specimens yielding false-reactive results on the Abbott 4th generation ARCHITECT HIV Ag/Ab Combo assay.

    Science.gov (United States)

    Lavoie, S; Caswell, D; Gill, M J; Kadkhoda, K; Charlton, C L; Levett, P N; Hatchette, T; Garceau, R; Maregmen, J; Mazzulli, T; Needle, R; Kadivar, K; Kim, J

    2018-04-12

    False-reactivity in HIV-negative specimens has been detected in HIV fourth-generation antigen/antibody or 'combo' assays which are able to detect both anti-HIV-1/HIV-2 antibodies and HIV-1 antigen. We sought to characterize these specimens and determine the effect of heterophilic interference. Specimens previously testing as false-reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay and re-tested on a different (Siemens ADVIA Centaur HIV Ag/Ab) assay. A subset of these specimens were also pre-treated with heterophilic blocking agents and re-tested on the Abbott assay. Here we report that 95% (252/264) of clinical specimens that were repeatedly reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay (S/Co range, 0.94-678) were negative when re-tested on a different fourth generation HIV combo assay (Siemens ADVIA Centaur HIV Ag/Ab). All 264 samples were subsequently confirmed to be HIV negative. On a small subset (57) of specimens with available volume, pre-treatment with two different reagents (HBT; Heterophilic Blocking Tube, NABT; Non-Specific Blocking Tube) designed to block heterophilic antibody interference either eliminated (HBT) or reduced (NABT) the false reactivity when re-tested on the ARCHITECT HIV Ag/Ab combo assay. Our results suggest that the Abbott ARCHITECT HIV Ag/Ab combo assay can be prone to heterophilic antibody interference. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  20. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Arun K. Nalla

    2016-03-01

    Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

  1. Meloxicam blocks neuroinflammation, but not depressive-like behaviors, in HIV-1 transgenic female rats.

    Directory of Open Access Journals (Sweden)

    Christina L Nemeth

    Full Text Available Adolescents living with human immunodeficiency virus (HIV comprise approximately 12% of the HIV-positive population worldwide. HIV-positive adolescents experience a higher rate of clinical depression, a greater risk of sexual and drug abuse behaviors, and a decreased adherence to highly active antiretroviral therapies (HAART. Using adolescent HIV-1 transgenic rats (HIV-1 tg that display related immune response alterations and pathologies, this study tested the hypothesis that developmental expression of HIV-1-related proteins induces a depressive-like phenotype that parallels a decrease in hippocampal cell proliferation and an increase in pro-inflammatory cytokine expression in the hippocampus. Consistent with this hypothesis, adolescent HIV-1 tg rats demonstrated a depressive-like behavioral phenotype, had decreased levels of cell proliferation, and exhibited elevated expression of monocyte chemotactic protein-1 (Mcp-1 in the hippocampus relative to controls. Subsequently, we tested the ability of meloxicam, a selective COX-2 inhibitor, to attenuate behavioral deficits via inflammatory mechanisms. Daily meloxicam treatments did not alter the behavioral profile despite effectively reducing hippocampal inflammatory gene expression. Together, these data support a biological basis for the co-morbid manifestation of depression in HIV-positive patients as early as in adolescence and suggest that modifications in behavior manifest independent of inflammatory activity in the hippocampus.

  2. Acceptance of a ready-to-use supplementary food by stable HIV ...

    African Journals Online (AJOL)

    2013-07-02

    Jul 2, 2013 ... by stable HIV-treated and HIV and tuberculosis. (co-infected)-treated ...... pulmonary tuberculosis and undernutrition: evidence for anabolic block in tuberculosis. Clin Sci.1998 ... among poor Mexican women. J Nutr. 2010 ...

  3. Geography should not be destiny: focusing HIV/AIDS implementation research and programs on microepidemics in US neighborhoods.

    Science.gov (United States)

    Nunn, Amy; Yolken, Annajane; Cutler, Blayne; Trooskin, Stacey; Wilson, Phill; Little, Susan; Mayer, Kenneth

    2014-05-01

    African Americans and Hispanics are disproportionately affected by the HIV/AIDS epidemic. Within the most heavily affected cities, a few neighborhoods account for a large share of new HIV infections. Addressing racial and economic disparities in HIV infection requires an implementation program and research agenda that assess the impact of HIV prevention interventions focused on increasing HIV testing, treatment, and retention in care in the most heavily affected neighborhoods in urban areas of the United States. Neighborhood-based implementation research should evaluate programs that focus on community mobilization, media campaigns, routine testing, linkage to and retention in care, and block-by-block outreach strategies.

  4. A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation.

    Directory of Open Access Journals (Sweden)

    Bridgette Janine Connell

    Full Text Available Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1-7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS as well as to an antibody (mAb 17b directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1.

  5. Expression of affordable microbicides to combat the spread of HIV pandemic

    CSIR Research Space (South Africa)

    Mawela, K

    2010-09-01

    Full Text Available activation, normal T expressed and secreted) show anti-HIV activity through their ability to block the HIV coreceptor CCR5 (Figure 1), and a number of N-terminally modified analogues of these proteins with much higher antiviral potency have been developed...

  6. Escape from Human Immunodeficiency Virus Type 1 (HIV-1 Entry Inhibitors

    Directory of Open Access Journals (Sweden)

    Carol D. Weiss

    2012-12-01

    Full Text Available The human immunodeficiency virus (HIV enters cells through a series of molecular interactions between the HIV envelope protein and cellular receptors, thus providing many opportunities to block infection. Entry inhibitors are currently being used in the clinic, and many more are under development. Unfortunately, as is the case for other classes of antiretroviral drugs that target later steps in the viral life cycle, HIV can become resistant to entry inhibitors. In contrast to inhibitors that block viral enzymes in intracellular compartments, entry inhibitors interfere with the function of the highly variable envelope glycoprotein as it continuously adapts to changing immune pressure and available target cells in the extracellular environment. Consequently, pathways and mechanisms of resistance for entry inhibitors are varied and often involve mutations across the envelope gene. This review provides a broad overview of entry inhibitor resistance mechanisms that inform our understanding of HIV entry and the design of new inhibitors and vaccines.

  7. Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors.

    Directory of Open Access Journals (Sweden)

    Christina Gavegnano

    2017-12-01

    Full Text Available Despite advances in the treatment of HIV infection with ART, elucidating strategies to overcome HIV persistence, including blockade of viral reservoir establishment, maintenance, and expansion, remains a challenge. T cell homeostasis is a major driver of HIV persistence. Cytokines involved in regulating homeostasis of memory T cells, the major hub of the HIV reservoir, trigger the Jak-STAT pathway. We evaluated the ability of tofacitinib and ruxolitinib, two FDA-approved Jak inhibitors, to block seeding and maintenance of the HIV reservoir in vitro. We provide direct demonstration for involvement of the Jak-STAT pathway in HIV persistence in vivo, ex vivo, and in vitro; pSTAT5 strongly correlates with increased levels of integrated viral DNA in vivo, and in vitro Jak inhibitors reduce the frequency of CD4+ T cells harboring integrated HIV DNA. We show that Jak inhibitors block viral production from infected cells, inhibit γ-C receptor cytokine (IL-15-induced viral reactivation from latent stores thereby preventing transmission of infectious particles to bystander activated T cells. These results show that dysregulation of the Jak-STAT pathway is associated with viral persistence in vivo, and that Jak inhibitors target key events downstream of γ-C cytokine (IL-2, IL-7 and IL-15 ligation to their receptors, impacting the magnitude of the HIV reservoir in all memory CD4 T cell subsets in vitro and ex vivo. Jak inhibitors represent a therapeutic modality to prevent key events of T cell activation that regulate HIV persistence and together, specific, potent blockade of these events may be integrated to future curative strategies.

  8. Identification of a D-amino acid decapeptide HIV-1 entry inhibitor

    International Nuclear Information System (INIS)

    Boggiano, Cesar; Jiang Shibo; Lu Hong; Zhao Qian; Liu Shuwen; Binley, James; Blondelle, Sylvie E.

    2006-01-01

    Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide DC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While DC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1α to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of DC13 implies additional mode(s) of action. These results suggest that DC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors

  9. Inhibition of HIV by Legalon-SIL is independent of its effect on cellular metabolism

    Energy Technology Data Exchange (ETDEWEB)

    McClure, Janela [Department of Laboratory Medicine, University of Washington, Seattle, WA (United States); Margineantu, Daciana H. [Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Sweet, Ian R. [Department of Medicine (Division of Metabolism, Endocrinology, and Nutrition), University of Washington, Seattle, WA (United States); Polyak, Stephen J., E-mail: polyak@uw.edu [Department of Laboratory Medicine, University of Washington, Seattle, WA (United States); Department of Global Health, University of Washington, Seattle, WA (United States)

    2014-01-20

    In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis. SbN, but not SIL inhibited glucose uptake. Exposure of T cells to SIL (but not SbN or metabolic inhibitors) during virus adsorption blocked HIV infection. Thus, both SbN and SIL rapidly perturb T cell metabolism in vitro, which may account for its anti-inflammatory and anti-proliferative effects that arise with prolonged exposure of cells. However, the metabolic effects are not involved in SIL's unique ability to block HIV entry. - Highlights: • Silibinin (SbN) and Legalon-SIL (SIL) are cytoprotective mixtures of natural products. • SbN and SIL reduce T cell oxidative phosphorylation and glycolysis in vitro. • SIL but not SbN blocks entry of multiple HIV isolates into T cells in vitro. • SIL's suppression of HIV appears independent of its effects on T cell metabolism. • Metabolic effects of SIL and SbN may be relevant in inflammatory diseases.

  10. Inhibition of HIV by Legalon-SIL is independent of its effect on cellular metabolism

    International Nuclear Information System (INIS)

    McClure, Janela; Margineantu, Daciana H.; Sweet, Ian R.; Polyak, Stephen J.

    2014-01-01

    In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis. SbN, but not SIL inhibited glucose uptake. Exposure of T cells to SIL (but not SbN or metabolic inhibitors) during virus adsorption blocked HIV infection. Thus, both SbN and SIL rapidly perturb T cell metabolism in vitro, which may account for its anti-inflammatory and anti-proliferative effects that arise with prolonged exposure of cells. However, the metabolic effects are not involved in SIL's unique ability to block HIV entry. - Highlights: • Silibinin (SbN) and Legalon-SIL (SIL) are cytoprotective mixtures of natural products. • SbN and SIL reduce T cell oxidative phosphorylation and glycolysis in vitro. • SIL but not SbN blocks entry of multiple HIV isolates into T cells in vitro. • SIL's suppression of HIV appears independent of its effects on T cell metabolism. • Metabolic effects of SIL and SbN may be relevant in inflammatory diseases

  11. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    Science.gov (United States)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  12. Effectiveness of condoms in preventing HIV transmission.

    Science.gov (United States)

    Pinkerton, S D; Abramson, P R

    1997-05-01

    The consistent use of latex condoms continues to be advocated for primary prevention of HIV infection despite limited quantitative evidence regarding the effectiveness of condoms in blocking the sexual transmission of HIV. Although recent meta-analyses of condom effectiveness suggest that condoms are 60 to 70% effective when used for HIV prophylaxis, these studies do not isolate consistent condom use, and therefore provide only a lower bound on the true effectiveness of correct and consistent condom use. A reexamination of HIV seroconversion studies suggests that condoms are 90 to 95% effective when used consistently, i.e. consistent condom users are 10 to 20 times less likely to become infected when exposed to the virus than are inconsistent or non-users. Similar results are obtained utilizing model-based estimation techniques, which indicate that condoms decrease the per-contact probability of male-to-female transmission of HIV by about 95%. Though imperfect, condoms provide substantial protection against HIV infection. Condom promotion therefore remains an important international priority in the fight against AIDS.

  13. HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific.

    Science.gov (United States)

    Evans, Edward L; Becker, Jordan T; Fricke, Stephanie L; Patel, Kishan; Sherer, Nathan M

    2018-04-01

    Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1 NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3.CX cells). 3T3.CX cells supported both Rev-independent and Rev-dependent viral gene expression and produced relatively robust levels of virus particles, confirming that CCNT1 and XPO1 represent the predominant blocks to these stages. Unexpectedly, however, 3T3.CX cells were remarkably resistant to virus-induced cytopathic effects observed in human cell lines, which we mapped to the viral protein Vif and its apparent species-specific capacity to induce G 2 /M cell cycle arrest. Vif was able to mediate rapid degradation of human APOBEC3G and the PPP2R5D regulatory B56 subunit of the PP2A phosphatase holoenzyme in mouse cells, thus demonstrating that Vif NL4-3 's modulation of the cell cycle can be functionally uncoupled from some of its other defined roles in CUL5-dependent protein degradation. Vif was also unable to induce G 2 /M cell cycle arrest in other nonhuman cell types, including cells derived from nonhuman primates, leading us to propose that one or more human-specific cofactors underpin Vif's ability to modulate the cell cycle. IMPORTANCE Cells derived from mice and other rodents exhibit profound blocks to HIV-1 replication, thus hindering the development of a low-cost small-animal model for studying HIV/AIDS. Here, we engineered otherwise-nonpermissive mouse cells to express HIV-1-compatible versions of two species-specific host dependency factors, cyclin T1 (CCNT1) and exportin-1 (XPO1) (3T3.CX cells). We show that 3T3.CX cells rescue HIV-1

  14. Neutralization epitopes on HIV pseudotyped with HTLV-I: Conservation of carbohydrate Epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  15. Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  16. Highlights from the HIV Cure and Reservoir Symposium, 11-12 September 2017, Ghent, Belgium.

    Science.gov (United States)

    Kint, Sam; Van Hecke, Clarissa; Cole, Basiel; Vandekerckhove, Linos; Sips, Magdalena

    2018-01-01

    For the second time, the HIV Cure Research Center (HCRC) at Ghent University organised the HIV Cure and Reservoir Symposium, in Ghent, Belgium, where in this two-day conference, virologists, molecular biologists, immunologists and clinicians presented the most recent achievements in the field of HIV cure, including data on therapeutic vaccines, HIV remission strategies such as 'shock and kill' or 'block and lock', benefits of early ART and potential of haematopoietic stem cell transplant in achieving cure. Furthermore, methods to characterise and quantify the HIV reservoir were discussed along with HIV reservoir characterisation in different body parts, including the central nervous system. An HIV activist and representative of a patients' agency also presented the patients' perspective on HIV cure. This report is a summary of all topics discussed during this symposium.

  17. Interactive Effects of Cocaine on HIV Infection: Implication in HIV-Associated Neurocognitive Disorder and NeuroAIDS

    Directory of Open Access Journals (Sweden)

    Santosh eDahal

    2015-09-01

    Full Text Available Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV, but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine in the brain, by blocking the dopamine transporters (DAT which is critical for dopamine homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to dopamine, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs, which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND. HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the Blood Brain Barrier (BBB in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies

  18. Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but not complete fusion

    Directory of Open Access Journals (Sweden)

    de la Vega Michelle

    2011-12-01

    Full Text Available Abstract Background We recently provided evidence that HIV-1 enters HeLa-derived TZM-bl and lymphoid CEMss cells by fusing with endosomes, whereas its fusion with the plasma membrane does not proceed beyond the lipid mixing step. The mechanism of restriction of HIV-1 fusion at the cell surface and/or the factors that aid the virus entry from endosomes remain unclear. Results We examined HIV-1 fusion with a panel of target cells lines and with primary CD4+ T cells. Kinetic measurements of fusion combined with time-resolved imaging of single viruses further reinforced the notion that HIV-1 enters the cells via endocytosis and fusion with endosomes. Furthermore, we attempted to deliberately redirect virus fusion to the plasma membrane, using two experimental strategies. First, the fusion reaction was synchronized by pre-incubating the viruses with cells at reduced temperature to allow CD4 and coreceptors engagement, but not the virus uptake or fusion. Subsequent shift to a physiological temperature triggered accelerated virus uptake followed by entry from endosomes, but did not permit fusion at the cell surface. Second, blocking HIV-1 endocytosis by a small-molecule dynamin inhibitor, dynasore, resulted in transfer of viral lipids to the plasma membrane without any detectable release of the viral content into the cytosol. We also found that a higher concentration of dynasore is required to block the HIV-endosome fusion compared to virus internalization. Conclusions Our results further support the notion that HIV-1 enters disparate cell types through fusion with endosomes. The block of HIV-1 fusion with the plasma membrane at a post-lipid mixing stage shows that this membrane is not conducive to fusion pore formation and/or enlargement. The ability of dynasore to interfere with the virus-endosome fusion suggests that dynamin could be involved in two distinct steps of HIV-1 entry - endocytosis and fusion within intracellular compartments.

  19. Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

    Science.gov (United States)

    Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

    2015-01-01

    HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

  20. Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women.

    Directory of Open Access Journals (Sweden)

    Ruizhong Shen

    Full Text Available Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT. Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.

  1. "Blocking" and "Filtering": a Commentary on Mobile Technology, Racism, and the Sexual Networks of Young Black MSM (YBMSM).

    Science.gov (United States)

    Winder, Terrell J A; Lea, Charles H

    2018-04-30

    While research investigates the role and influence of geo-social networking (GSN) applications on HIV, less is known about the impact of GSN functions on disease transmission. In our formative research on young Black men who have sex with men's (YBMSM) technology use patterns and preferences for a smartphone-based HIV prevention intervention, we found that study participants used GSN "block" and "filter" functions as protective mechanisms against racism and racial sexual discrimination. Yet, we suggest that these functions may unintentionally create restrictive sexual networks that likely increase their risk for disease transmission. As such, we contend that attention to the unintended effects of these protective mechanisms against racism on GSN applications is fundamentally a public health issue that requires more research and explicit intervention. Ultimately, we use this work to hypothesize the role of blocking and filtering as a strategy to avoid racism on GSN applications that may partly explain HIV disparities among YBMSM.

  2. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses.

    Science.gov (United States)

    Gao, Daxing; Wu, Jiaxi; Wu, You-Tong; Du, Fenghe; Aroh, Chukwuemika; Yan, Nan; Sun, Lijun; Chen, Zhijian J

    2013-08-23

    Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse-transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus, and simian immunodeficiency virus. These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.

  3. The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids.

    Directory of Open Access Journals (Sweden)

    Robin G Mansour

    Full Text Available Tenascin-C (TNC is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals.

  4. Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants

    Directory of Open Access Journals (Sweden)

    Song Xinming

    2009-08-01

    Full Text Available Abstract Background Highly active anti-retroviral therapy (HAART is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication. Methods Crude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc was used to identify potential anti-HIV mechanisms of these extracts. Results Two extracts, one from Euphorbiaceae, Trigonostema xyphophylloides (TXE and one from Dipterocarpaceae, Vatica astrotricha (VAD inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus. Conclusion These results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking

  5. Inhibition of human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1) infectivity with a broad range of lectins

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Vestergaard, B F

    1991-01-01

    Five lectins with specificity for N- and O-linked oligosaccharides were examined for inhibition of HIV-1 and HSV-1 infectivity in vitro. HIV-1 isolate HTLVIIIB was preincubated with lectin and subsequently inoculated onto MT-4 cells. Lectins specific for N-linked oligosaccharides blocked HIV infe...

  6. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

    Science.gov (United States)

    Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

    2014-07-29

    Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. A multimodal assessment of driving performance in HIV infection.

    Science.gov (United States)

    Marcotte, T D; Wolfson, T; Rosenthal, T J; Heaton, R K; Gonzalez, R; Ellis, R J; Grant, I

    2004-10-26

    To examine if HIV-seropositive (HIV+) individuals are at risk for impaired driving. Sixty licensed drivers (40 HIV+, 20 HIV-) completed a neuropsychological (NP) test battery and driving assessments. Eleven HIV+ subjects were NP-impaired. Driving-related skills were assessed using 1) two driving simulations (examining accident avoidance and navigational abilities), 2) the Useful Field of View (UFOV) test, and 3) an on-road evaluation. HIV+ NP-impaired subjects had greater difficulty than cognitively intact subjects on all driving measures, whereas the HIV- and HIV+ NP-normal groups performed similarly. On the UFOV, the HIV+ NP-impaired group had worse performance on Visual Processing and Divided Attention tasks but not in overall risk classification. They also had a higher number of simulator accidents (1.3 vs 2.0; p = 0.03), were less efficient at completing the navigation task (3.2 vs 9.2 blocks; p = 0.001), and were more likely to fail the on-road evaluation (6 vs 36%; p = 0.02). Impairment in Executive Functioning was the strongest NP predictor of failing the on-road drive test. NP performance and both simulations independently contributed to a model predicting 48% of the variance in on-road performance. HIV+ NP-impaired individuals are at increased risk for on-road driving impairments, whereas HIV+ individuals with normal cognition are not at a significantly higher risk than HIV- subjects. Executive Functioning is most strongly associated with impaired on-road performance. Cognitive and simulator testing may each provide data in identifying driving-impaired individuals.

  8. Associations between HIV-related stigma, racial discrimination, gender discrimination, and depression among HIV-positive African, Caribbean, and Black women in Ontario, Canada.

    Science.gov (United States)

    Logie, Carmen; James, Llana; Tharao, Wangari; Loutfy, Mona

    2013-02-01

    Abstract African, Caribbean, and Black (ACB) women are greatly overrepresented in new HIV infections in comparison with Canada's general population. Social and structural factors such as HIV-related stigma, gender discrimination, and racial discrimination converge to increase vulnerability to HIV infection among ACB women by reducing access to HIV prevention services. Stigma and discrimination also present barriers to treatment, care, and support and may contribute to mental health problems. We administered a cross-sectional survey to HIV-positive ACB women (n=173) across Ontario in order to examine the relationships between HIV-related stigma, gender discrimination, racial discrimination, and depression. One-third of participants reported moderate/severe depression scores using the Beck Depression Inventory Fast-Screen guidelines. Hierarchical block regression, moderation, and mediation analyses were conducted to measure associations between independent (HIV-related stigma, gender discrimination, racial discrimination), moderator/mediator (social support, resilient coping), and dependent (depression) variables. Findings included: (1) HIV-related stigma was associated with increased depression; (2) resilient coping was associated with reduced depression but did not moderate the influence of HIV-related stigma on depression; and (3) the effects of HIV-related stigma on depression were partially mediated through resilient coping. HIV-related stigma, gender discrimination, and racial discrimination were significantly correlated with one another and with depression, highlighting the salience of examining multiple intersecting forms of stigma. Generalizability of findings may be limited due to nonrandom sampling. Findings emphasize the importance of multi-component interventions, including building resilient coping skills, mental health promotion and assessment, and stigma reduction programs.

  9. Flazinamide, a novel β-carboline compound with anti-HIV actions

    International Nuclear Information System (INIS)

    Wang Yunhua; Tang Jianguo; Wang Ruirui; Yang Liumeng; Dong Zejun; Du Li; Shen Xu; Liu Jikai; Zheng Yongtang

    2007-01-01

    A β-carboline compound, flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of flazin, flazinamide [1-(5'- hydromethyl-2'-furyl)-β-carboline-3-carboxamide] was synthesized and its anti-HIV activities were evaluated in the present study. The cytotoxicity of flazinamide was about 4.1-fold lower than that of flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38 μM, the EC50 of flazinamide was about 6.2-fold lower than that of flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89 μM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77 μM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and flazinamide might interfere in the early stage of HIV life cycle

  10. HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

    Science.gov (United States)

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

    2015-01-01

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was Maraviroc. This HIV entry inhibitor targets the host cell CCR5 coreceptor and was highly active against both untreated and semen-exposed HIV. These data help explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

  11. Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Kara G Lassen

    2006-07-01

    Full Text Available HIV-1 latency in resting CD4+ T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART. We describe here a novel post-transcriptional block in HIV-1 gene expression in resting CD4+ T cells from patients on HAART. This block involves the aberrant localization of multiply spliced (MS HIV-1 RNAs encoding the critical positive regulators Tat and Rev. Although these RNAs had no previously described export defect, we show that they exhibit strict nuclear localization in resting CD4+ T cells from patients on HAART. Overexpression of the transcriptional activator Tat from non-HIV vectors allowed virus production in these cells. Thus, the nuclear retention of MS HIV-1 RNA interrupts a positive feedback loop and contributes to the non-productive nature of infection of resting CD4+ T cells. To define the mechanism of nuclear retention, proteomic analysis was used to identify proteins that bind MS HIV-1 RNA. Polypyrimidine tract binding protein (PTB was identified as an HIV-1 RNA-binding protein differentially expressed in resting and activated CD4+ T cells. Overexpression of PTB in resting CD4+ T cells from patients on HAART allowed cytoplasmic accumulation of HIV-1 RNAs. PTB overexpression also induced virus production by resting CD4+ T cells. Virus culture experiments showed that overexpression of PTB in resting CD4+ T cells from patients on HAART allowed release of replication-competent virus, while preserving a resting cellular phenotype. Whether through effects on RNA export or another mechanism, the ability of PTB to reverse latency without inducing cellular activation is a result with therapeutic implications.

  12. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.

    Directory of Open Access Journals (Sweden)

    Ussama M Abdel-Motal

    Full Text Available Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS.This study tested the hypothesis that adeno-associated virus (AAV-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc, or "minibody" was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1(bal in an organotypic human vaginal epithelial cell (VEC model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP.This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.

  13. Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR RNA.

    Directory of Open Access Journals (Sweden)

    Matthew S Lalonde

    2011-05-01

    Full Text Available The RNA response element TAR plays a critical role in HIV replication by providing a binding site for the recruitment of the viral transactivator protein Tat. Using a structure-guided approach, we have developed a series of conformationally-constrained cyclic peptides that act as structural mimics of the Tat RNA binding region and block Tat-TAR interactions at nanomolar concentrations in vitro. Here we show that these compounds block Tat-dependent transcription in cell-free systems and in cell-based reporter assays. The compounds are also cell permeable, have low toxicity, and inhibit replication of diverse HIV-1 strains, including both CXCR4-tropic and CCR5-tropic primary HIV-1 isolates of the divergent subtypes A, B, C, D and CRF01_AE. In human peripheral blood mononuclear cells, the cyclic peptidomimetic L50 exhibited an IC(50 ∼250 nM. Surprisingly, inhibition of LTR-driven HIV-1 transcription could not account for the full antiviral activity. Timed drug-addition experiments revealed that L-50 has a bi-phasic inhibition curve with the first phase occurring after HIV-1 entry into the host cell and during the initiation of HIV-1 reverse transcription. The second phase coincides with inhibition of HIV-1 transcription. Reconstituted reverse transcription assays confirm that HIV-1 (- strand strong stop DNA synthesis is blocked by L50-TAR RNA interactions in-vitro. These findings are consistent with genetic evidence that TAR plays critical roles both during reverse transcription and during HIV gene expression. Our results suggest that antiviral drugs targeting TAR RNA might be highly effective due to a dual inhibitory mechanism.

  14. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    Science.gov (United States)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  15. Clinical outcomes and immune benefits of anti-epileptic drug therapy in HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Krentz Hartmut B

    2010-06-01

    Full Text Available Abstract Background Anti-epileptic drugs (AEDs are frequently prescribed to persons with HIV/AIDS receiving combination antiretroviral therapy (cART although the extent of AED use and their interactions with cART are uncertain. Herein, AED usage, associated toxicities and immune consequences were investigated. Methods HIV replication was analysed in proliferating human T cells during AED exposure. Patients receiving AEDs in a geographically-based HIV care program were assessed using clinical and laboratory variables in addition to assessing AED indication, type, and cumulative exposures. Results Valproate suppressed proliferation in vitro of both HIV-infected and uninfected T cells (p 0.05 but AED exposures did not affect HIV production in vitro. Among 1345 HIV/AIDS persons in active care between 2001 and 2007, 169 individuals were exposed to AEDs for the following indications: peripheral neuropathy/neuropathic pain (60%, seizure/epilepsy (24%, mood disorder (13% and movement disorder (2%. The most frequently prescribed AEDs were calcium channel blockers (gabapentin/pregabalin, followed by sodium channel blockers (phenytoin, carbamazepine, lamotrigine and valproate. In a nested cohort of 55 AED-treated patients receiving cART and aviremic, chronic exposure to sodium and calcium channel blocking AEDs was associated with increased CD4+ T cell levels (p 0.05 with no change in CD8+ T cell levels over 12 months from the beginning of AED therapy. Conclusions AEDs were prescribed for multiple indications without major adverse effects in this population but immune status in patients receiving sodium or calcium channel blocking drugs was improved.

  16. Potential mechanisms for cell-based gene therapy to treat HIV/AIDS.

    Science.gov (United States)

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-02-01

    An estimated 35 million people are infected with HIV worldwide. Anti-retroviral therapy (ART) has reduced the morbidity and mortality of HIV-infected patients but efficacy requires strict adherence and the treatment is not curative. Most importantly, the emergence of drug-resistant virus strains and drug toxicity can restrict the long-term therapeutic efficacy in some patients. Therefore, novel treatment strategies that permanently control or eliminate the virus and restore the damaged immune system are required. Gene therapy against HIV infection has been the topic of intense investigations for the last two decades because it can theoretically provide such a durable anti-HIV control. In this review we discuss two major gene therapy strategies to combat HIV. One approach aims to kill HIV-infected cells and the other is based on the protection of cells from HIV infection. We discuss the underlying molecular mechanisms for candidate approaches to permanently block HIV infection, including the latest strategies and future therapeutic applications. Hematopoietic stem cell-based gene therapy for HIV/AIDS may eventually become an alternative for standard ART and should ideally provide a functional cure in which the virus is durably controlled without medication. Recent results from preclinical research and early-stage clinical trials support the feasibility and safety of this novel strategy.

  17. Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors

    Directory of Open Access Journals (Sweden)

    Simmonds Peter

    2008-01-01

    Full Text Available Abstract Background HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node. Results R5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542, but with increased resistance to the anti-CD4 monoclonal antibody (mab, Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and sensitivity to CCR5 antagonists or to gp41 specific reagents. Intriguingly, there was a relationship between increasing macrophage-tropism and increased sensitivity to the CD4 binding site mab, b12, but decreased sensitivity to 2G12, a mab that binds a glycan complex on gp120. Conclusion Variation in R5 macrophage-tropism is caused by envelope variation that predominantly influences sensitivity to reagents that block gp120:CD4 interactions. Such variation has important implications for therapy using viral entry inhibitors and for the design of envelope antigens for vaccines.

  18. Guatemalan plants extracts as virucides against HIV-1 infection.

    Science.gov (United States)

    Bedoya, Luis M; Alvarez, Amparo; Bermejo, Mercedes; González, Nuria; Beltrán, Manuela; Sánchez-Palomino, Sonsoles; Cruz, Sully M; Gaitán, Isabel; del Olmo, Esther; Escarcena, Ricardo; García, Pablo A; Cáceres, Armando; San Feliciano, Arturo; Alcamí, José

    2008-06-01

    Prevention methods to avoid transmission of pathogens, including HIV, are crucial in the control of infectious diseases, not only to block epidemic spread but to avoid long-term treatments leading to emergence of resistances and drug associated side effects. Together with vaccine development, the discovery of new virucidal agents represents a research priority in this setting. In the screening of new compounds with antiviral activity, three Guatemalan plant extracts from Justicia reptans, Neurolaena lobata and Pouteria viridis were evaluated with a classic antiviral assay and were found to inhibit HIV replication. This activity was corroborated by an original recombinant virus assay, leading us to perform a deeper study of the virucidal activity. Active fractions were non-toxic in vitro and also inhibited other enveloped viruses. Moreover, these fractions were able to inhibit the transfer of HIV from dendritic cells (DCs) to lymphocytes, that represents the main way of HIV spread in vivo.

  19. Demonstration of a novel HIV-1 restriction phenotype from a human T cell line.

    Directory of Open Access Journals (Sweden)

    Yanxing Han

    2008-07-01

    Full Text Available Although retroviruses may invade host cells, a productive infection can be established only after the virus counteracts inhibition from different types of host restriction factors. Fv1, APOBEC3G/F, TRIM5alpha, ZAP, and CD317 inhibit the replication of different retroviruses by interfering with viral uncoating, reverse transcription, nuclear import, RNA stability, and release. In humans, although APOBEC3G/3F and CD317 block HIV-1 replication, their antiviral activities are neutralized by viral proteins Vif and Vpu. So far, no human gene has been found to effectively block wild type HIV-1 replication under natural condition. Thus, identification of such a gene product would be of great medical importance for the development of HIV therapies.In this study, we discovered a new type of host restriction against the wild type HIV-1 from a CD4/CXCR4 double-positive human T cell line. We identified a CEM-derived cell line (CEM.NKR that is highly resistant to productive HIV-1 infection. Viral production was reduced by at least 1000-fold when compared to the other permissive human T cell lines such as H9, A3.01, and CEM-T4. Importantly, this resistance was evident at extremely high multiplicity of infection. Further analyses demonstrated that HIV-1 could finish the first round of replication in CEM.NKR cells, but the released virions were poorly infectious. These virions could enter the target cells, but failed to initiate reverse transcription. Notably, this restriction phenotype was also present in CEM.NKR and 293T heterokaryons.These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s. Further characterization of this novel gene product(s will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1.

  20. Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

    Science.gov (United States)

    Shan, Liang; Siliciano, Robert F.

    2014-01-01

    Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

  1. HIV-1 nef suppression by virally encoded microRNA

    Directory of Open Access Journals (Sweden)

    Brisibe Ebiamadon

    2004-12-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are 21~25-nucleotides (nt long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi, depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs inhibited the transcription of HIV-1. Results Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA that corresponded to a predicted nef miRNA (~25 nt, miR-N367 can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2. In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. Conclusions These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

  2. HIPdb: a database of experimentally validated HIV inhibiting peptides.

    Science.gov (United States)

    Qureshi, Abid; Thakur, Nishant; Kumar, Manoj

    2013-01-01

    Besides antiretroviral drugs, peptides have also demonstrated potential to inhibit the Human immunodeficiency virus (HIV). For example, T20 has been discovered to effectively block the HIV entry and was approved by the FDA as a novel anti-HIV peptide (AHP). We have collated all experimental information on AHPs at a single platform. HIPdb is a manually curated database of experimentally verified HIV inhibiting peptides targeting various steps or proteins involved in the life cycle of HIV e.g. fusion, integration, reverse transcription etc. This database provides experimental information of 981 peptides. These are of varying length obtained from natural as well as synthetic sources and tested on different cell lines. Important fields included are peptide sequence, length, source, target, cell line, inhibition/IC(50), assay and reference. The database provides user friendly browse, search, sort and filter options. It also contains useful services like BLAST and 'Map' for alignment with user provided sequences. In addition, predicted structure and physicochemical properties of the peptides are also included. HIPdb database is freely available at http://crdd.osdd.net/servers/hipdb. Comprehensive information of this database will be helpful in selecting/designing effective anti-HIV peptides. Thus it may prove a useful resource to researchers for peptide based therapeutics development.

  3. FAITH – Fast Assembly Inhibitor Test for HIV

    Energy Technology Data Exchange (ETDEWEB)

    Hadravová, Romana [Institute of Organic Chemistry and Biochemistry IOCB Research Centre & Gilead Sciences, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague (Czech Republic); Rumlová, Michaela, E-mail: michaela.rumlova@vscht.cz [Institute of Organic Chemistry and Biochemistry IOCB Research Centre & Gilead Sciences, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague (Czech Republic); Department of Biotechnology, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague (Czech Republic); Ruml, Tomáš, E-mail: tomas.ruml@vscht.cz [Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, 166 28 Prague (Czech Republic)

    2015-12-15

    Due to the high number of drug-resistant HIV-1 mutants generated by highly active antiretroviral therapy (HAART), there is continuing demand for new types of inhibitors. Both the assembly of the Gag polyprotein into immature and mature HIV-1 particles are attractive candidates for the blocking of the retroviral life cycle. Currently, no therapeutically-used assembly inhibitor is available. One possible explanation is the lack of a reliable and simple assembly inhibitor screening method. To identify compounds potentially inhibiting the formation of both types of HIV-1 particles, we developed a new fluorescent high-throughput screening assay. This assay is based on the quantification of the assembly efficiency in vitro in a 96-well plate format. The key components of the assay are HIV-1 Gag-derived proteins and a dual-labelled oligonucleotide, which emits fluorescence only when the assembly of retroviral particles is inhibited. The method was validated using three (CAI, BM2, PF74) reported assembly inhibitors. - Highlights: • Allows screening of assembly inhibitors of both mature and immature HIV-1 particles. • Based on Gag-derived proteins with CA in mature or immature conformation. • Simple and sensitive method suitable for high-throughput screening of inhibitors. • Unlike in other HIV assembly methods, works under physiological conditions. • No washing steps are necessary.

  4. FAITH – Fast Assembly Inhibitor Test for HIV

    International Nuclear Information System (INIS)

    Hadravová, Romana; Rumlová, Michaela; Ruml, Tomáš

    2015-01-01

    Due to the high number of drug-resistant HIV-1 mutants generated by highly active antiretroviral therapy (HAART), there is continuing demand for new types of inhibitors. Both the assembly of the Gag polyprotein into immature and mature HIV-1 particles are attractive candidates for the blocking of the retroviral life cycle. Currently, no therapeutically-used assembly inhibitor is available. One possible explanation is the lack of a reliable and simple assembly inhibitor screening method. To identify compounds potentially inhibiting the formation of both types of HIV-1 particles, we developed a new fluorescent high-throughput screening assay. This assay is based on the quantification of the assembly efficiency in vitro in a 96-well plate format. The key components of the assay are HIV-1 Gag-derived proteins and a dual-labelled oligonucleotide, which emits fluorescence only when the assembly of retroviral particles is inhibited. The method was validated using three (CAI, BM2, PF74) reported assembly inhibitors. - Highlights: • Allows screening of assembly inhibitors of both mature and immature HIV-1 particles. • Based on Gag-derived proteins with CA in mature or immature conformation. • Simple and sensitive method suitable for high-throughput screening of inhibitors. • Unlike in other HIV assembly methods, works under physiological conditions. • No washing steps are necessary.

  5. Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine: testosterone and ICI 182,780 sensitive mechanism

    Directory of Open Access Journals (Sweden)

    Mactutus Charles F

    2005-06-01

    Full Text Available Abstract Background HIV Associated Dementia (HAD is a common complication of human immunodeficiency virus (HIV infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, to produce a significant synergistic neurotoxicity. Using this model system, the neuroprotective potential of gonadal steroids was investigated. Results 17β-Estradiol (17β-E2, but not 17α-estradiol (17α-E2, was protective against this combined neurotoxicity. Progesterone (PROG afforded limited neuroprotection, as did dihydrotestosterone (DHT. The efficacy of 5α-testosterone (T-mediated neuroprotection was robust, similar to that provided by 17β-E2. In the presence of the specific estrogen receptor (ER antagonist, ICI-182,780, T's neuroprotection was completely blocked. Thus, T acts through the ER to provide neuroprotection against HIV proteins and cocaine. Interestingly, cholesterol also demonstrated concentration-dependent neuroprotection, possibly attributable to cholesterol's serving as a steroid hormone precursor in neurons. Conclusion Collectively, the present data indicate that cocaine has a robust interaction with the HIV proteins gp120 and Tat that produces severe neurotoxicity, and this toxicity can be blocked through pretreatment with ER agonists.

  6. Interferon α subtypes in HIV infection.

    Science.gov (United States)

    Sutter, Kathrin; Dickow, Julia; Dittmer, Ulf

    2018-02-13

    Type I interferons (IFN), which are immediately induced after most virus infections, are central for direct antiviral immunity and link innate and adaptive immune responses. However, several viruses have evolved strategies to evade the IFN response by preventing IFN induction or blocking IFN signaling pathways. Thus, therapeutic application of exogenous type I IFN or agonists inducing type I IFN responses are a considerable option for future immunotherapies against chronic viral infections. An important part of the type I IFN family are 12 IFNα subtypes, which all bind the same receptor, but significantly differ in their biological activities. Up to date only one IFNα subtype (IFNα2) is being used in clinical treatment against chronic virus infections, however its therapeutic success rate is rather limited, especially during Human Immunodeficiency Virus (HIV) infection. Recent studies addressed the important question if other IFNα subtypes would be more potent against retroviral infections in in vitro and in vivo experiments. Indeed, very potent IFNα subtypes were defined and their antiviral and immunomodulatory properties were characterized. In this review we summarize the recent findings on the role of individual IFNα subtypes during HIV and Simian Immunodeficiency Virus infection. This includes their induction during HIV/SIV infection, their antiretroviral activity and the regulation of immune response against HIV by different IFNα subtypes. The findings might facilitate novel strategies for HIV cure or functional cure studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. An efficient, block-by-block algorithm for inverting a block tridiagonal, nearly block Toeplitz matrix

    International Nuclear Information System (INIS)

    Reuter, Matthew G; Hill, Judith C

    2012-01-01

    We present an algorithm for computing any block of the inverse of a block tridiagonal, nearly block Toeplitz matrix (defined as a block tridiagonal matrix with a small number of deviations from the purely block Toeplitz structure). By exploiting both the block tridiagonal and the nearly block Toeplitz structures, this method scales independently of the total number of blocks in the matrix and linearly with the number of deviations. Numerical studies demonstrate this scaling and the advantages of our method over alternatives.

  8. The pathogenesis of HIV infection: stupid may not be so dumb after all

    Directory of Open Access Journals (Sweden)

    Smith Stephen M

    2006-09-01

    Full Text Available Abstract In the mid-1990's, researchers hypothesized, based on new viral load data, that HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non-human primate studies has raised doubts about this model of HIV-1 pathogenesis. Despite having high levels of viremia, most SIV infections are well tolerated by their natural hosts. Two recent studies of these models provide information, which may be useful in determining how HIV-1 causes CD4+ T-cell loss. A full understanding of pathogenesis may lead to novel therapies, which preserve the immune system without blocking virus replication.

  9. Punica granatum (Pomegranate juice provides an HIV-1 entry inhibitor and candidate topical microbicide

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2004-10-01

    Full Text Available Abstract Background For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. Methods Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1 infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2 binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. Results HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. Conclusion These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored.

  10. N-terminally truncated POM121C inhibits HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Hideki Saito

    Full Text Available Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1. These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.

  11. Inhibition of HIV-1 infection by aqueous extracts of Prunella vulgaris L.

    Directory of Open Access Journals (Sweden)

    McCoy Joe-Ann

    2011-04-01

    Full Text Available Abstract Background The mint family (Lamiaceae produces a wide variety of constituents with medicinal properties. Several family members have been reported to have antiviral activity, including lemon balm (Melissa officinalis L., sage (Salvia spp., peppermint (Mentha × piperita L., hyssop (Hyssopus officinalis L., basil (Ocimum spp. and self-heal (Prunella vulgaris L.. To further characterize the anti-lentiviral activities of Prunella vulgaris, water and ethanol extracts were tested for their ability to inhibit HIV-1 infection. Results Aqueous extracts contained more anti-viral activity than did ethanol extracts, displaying potent antiviral activity against HIV-1 at sub μg/mL concentrations with little to no cellular cytotoxicity at concentrations more than 100-fold higher. Time-of-addition studies demonstrated that aqueous extracts were effective when added during the first five hours following initiation of infection, suggesting that the botanical constituents were targeting entry events. Further analysis revealed that extracts inhibited both virus/cell interactions and post-binding events. While only 40% inhibition was maximally achieved in our virus/cell interaction studies, extract effectively blocked post-binding events at concentrations similar to those that blocked infection, suggesting that it was targeting of these latter steps that was most important for mediating inhibition of virus infectivity. Conclusions We demonstrate that aqueous P. vulgaris extracts inhibited HIV-1 infectivity. Our studies suggest that inhibition occurs primarily by interference of early, post-virion binding events. The ability of aqueous extracts to inhibit early events within the HIV life cycle suggests that these extracts, or purified constituents responsible for the antiviral activity, are promising microbicides and/or antivirals against HIV-1.

  12. Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

    International Nuclear Information System (INIS)

    Managlia, Elizabeth Z.; Landay, Alan; Al-Harthi, Lena

    2006-01-01

    Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NFκB. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated induction of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFNγ, all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator

  13. TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Lee Adam Wheeler

    2016-05-01

    Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

  14. Epigenetic regulation of HIV-1 latency: focus on polycomb group (PcG) proteins.

    Science.gov (United States)

    Khan, Sheraz; Iqbal, Mazhar; Tariq, Muhammad; Baig, Shahid M; Abbas, Wasim

    2018-01-01

    HIV-1 latency allows the virus to persist until reactivation, in a transcriptionally silent form in its cellular reservoirs despite the presence of effective cART. Such viral persistence represents a major barrier to HIV eradication since treatment interruption leads to rebound plasma viremia. Polycomb group (PcG) proteins have recently got a considerable attention in regulating HIV-1 post-integration latency as they are involved in the repression of proviral gene expression through the methylation of histones. This epigenetic regulation plays an important role in the establishment and maintenance of HIV-1 latency. In fact, PcG proteins act in complexes and modulate the epigenetic signatures of integrated HIV-1 promoter. Key role played by PcG proteins in the molecular control of HIV-1 latency has led to hypothesize that PcG proteins may represent a valuable target for future HIV-1 therapy in purging HIV-1 reservoirs. In this regard, various small molecules have been synthesized or explored to specifically block the epigenetic activity of PcG. In this review, we will highlight the possible therapeutic approaches to achieve either a functional or sterilizing cure of HIV-1 infection with special focus on histone methylation by PcG proteins together with current and novel pharmacological approaches to reactivate HIV-1 from latency that could ultimately lead towards a better clearance of viral latent reservoirs.

  15. Understanding the drivers of interprofessional collaborative practice among HIV primary care providers and case managers in HIV care programmes.

    Science.gov (United States)

    Mavronicolas, Heather A; Laraque, Fabienne; Shankar, Arti; Campbell, Claudia

    2017-05-01

    Care coordination programmes are an important aspect of HIV management whose success depends largely on HIV primary care provider (PCP) and case manager collaboration. Factors influencing collaboration among HIV PCPs and case managers remain to be studied. The study objective was to test an existing theoretical model of interprofessional collaborative practice and determine which factors play the most important role in facilitating collaboration. A self-administered, anonymous mail survey was sent to HIV PCPs and case managers in New York City. An adapted survey instrument elicited information on demographic, contextual, and perceived social exchange (trustworthiness, role specification, and relationship initiation) characteristics. The dependent variable, perceived interprofessional practice, was constructed from a validated scale. A sequential block wise regression model specifying variable entry order examined the relative importance of each group of factors and of individual variables. The analysis showed that social exchange factors were the dominant drivers of collaboration. Relationship initiation was the most important predictor of interprofessional collaboration. Additional influential factors included organisational leadership support of collaboration, practice settings, and frequency of interprofessional meetings. Addressing factors influencing collaboration among providers will help public health programmes optimally design their structural, hiring, and training strategies to foster effective social exchanges and promote collaborative working relationships.

  16. Spatial Epidemiology of HIV among Injection Drug Users in Tijuana, Mexico.

    Science.gov (United States)

    Brouwer, Kimberly C; Rusch, Melanie L; Weeks, John R; Lozada, Remedios; Vera, Alicia; Magis-Rodríguez, Carlos; Strathdee, Steffanie A

    2012-01-01

    The northwest border city of Tijuana is Mexico's fifth largest and is experiencing burgeoning drug use and human immunodeficiency virus (HIV) epidemics. Since local geography influences disease risk, we explored the spatial distribution of HIV among injection drug users (IDUs). From 2006-2007, 1056 IDUs were recruited using respondent-driven sampling, and then followed for eighteen months. Participants underwent semi-annual surveys, mapping, and testing for HIV, tuberculosis, and syphilis. Using Average Nearest Neighbor and Getis-Ord Gi* statistics, locations where participants lived, worked, bought and injected drugs were compared with HIV status and environmental and behavioral factors. Median age was thirty-seven years; 85 percent were male. Females had higher HIV prevalence than males (10.2 percent vs. 3.4 percent; p =0.001). HIV cases at baseline ( n =47) most strongly clustered by drug injection sites ( Z -Score -6.173; p light district. Spatial correlates of HIV included syphilis infection, female gender, younger age, increased hours on the street per day, and higher number of injection partners. Almost all HIV seroconverters injected within a 2.5 block radius of each other immediately prior to seroconversion. Only history of syphilis infection and female gender were strongly associated with HIV in the area where incident cases injected. Directional trends suggested a largely static epidemic until July-December 2008, when HIV spread to the southeast, possibly related to intensified violence and policing that spiked in the latter half of 2008. While clustering allows for targeting interventions, the dynamic nature of epidemics suggests the importance of mobile treatment and harm reduction programs.

  17. Tackling HIV Persistence: Pharmacological versus CRISPR-Based Shock Strategies.

    Science.gov (United States)

    Darcis, Gilles; Das, Atze T; Berkhout, Ben

    2018-03-29

    Jan Svoboda studied aspects of viral latency, in particular with respect to disease induction by avian RNA tumor viruses, which were later renamed as part of the extended retrovirus family. The course of retroviral pathogenesis is intrinsically linked to their unique property of integrating the DNA copy of the retroviral genome into that of the host cell, thus forming the provirus. Retroviral latency has recently become of major clinical interest to allow a better understanding of why we can effectively block the human immunodeficiency virus type 1 (HIV-1) in infected individuals with antiviral drugs, yet never reach a cure. We will discuss HIV-1 latency and its direct consequence-the formation of long-lasting HIV-1 reservoirs. We next focus on one of the most explored strategies in tackling HIV-1 reservoirs-the "shock and kill" strategy-which describes the broadly explored pharmacological way of kicking the latent provirus, with subsequent killing of the virus-producing cell by the immune system. We furthermore present how the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system can be harnessed to reach the same objective by reactivating HIV-1 gene expression from latency. We will review the benefits and drawbacks of these different cure strategies.

  18. Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains

    International Nuclear Information System (INIS)

    Xiang Shihua; Wang Liping; Abreu, Mariam; Huang, C.-C.; Kwong, Peter D.; Rosenberg, Eric; Robinson, James E.; Sodroski, Joseph

    2003-01-01

    Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the β19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies

  19. Identification of dual-tropic HIV-1 using evolved neural networks.

    Science.gov (United States)

    Fogel, Gary B; Lamers, Susanna L; Liu, Enoch S; Salemi, Marco; McGrath, Michael S

    2015-11-01

    Blocking the binding of the envelope HIV-1 protein to immune cells is a popular concept for development of anti-HIV therapeutics. R5 HIV-1 binds CCR5, X4 HIV-1 binds CXCR4, and dual-tropic HIV-1 can bind either coreceptor for cellular entry. R5 viruses are associated with early infection and over time can evolve to X4 viruses that are associated with immune failure. Dual-tropic HIV-1 is less studied; however, it represents functional antigenic intermediates during the transition of R5 to X4 viruses. Viral tropism is linked partly to the HIV-1 envelope V3 domain, where the amino acid sequence helps dictate the receptor a particular virus will target; however, using V3 sequence information to identify dual-tropic HIV-1 isolates has remained difficult. Our goal in this study was to elucidate features of dual-tropic HIV-1 isolates that assist in the biological understanding of dual-tropism and develop an approach for their detection. Over 1559 HIV-1 subtype B sequences with known tropisms were analyzed. Each sequence was represented by 73 structural, biochemical and regional features. These features were provided to an evolved neural network classifier and evaluated using balanced and unbalanced data sets. The study resolved R5X4 viruses from R5 with an accuracy of 81.8% and from X4 with an accuracy of 78.8%. The approach also identified a set of V3 features (hydrophobicity, structural and polarity) that are associated with tropism transitions. The ability to distinguish R5X4 isolates will improve computational tropism decisions for R5 vs. X4 and assist in HIV-1 research and drug development efforts. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. CD4-specific designed ankyrin repeat proteins are novel potent HIV entry inhibitors with unique characteristics.

    Directory of Open Access Journals (Sweden)

    Andreas Schweizer

    2008-07-01

    Full Text Available Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins-high physical stability, specificity and low production costs-with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development.

  1. HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction.

    Science.gov (United States)

    Gargan, Siobhan; Ahmed, Suaad; Mahony, Rebecca; Bannan, Ciaran; Napoletano, Silvia; O'Farrelly, Cliona; Borrow, Persephone; Bergin, Colm; Stevenson, Nigel J

    2018-04-01

    Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-α-mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a functional consequence of this HIV-1-mediated immune evasion strategy. Interestingly, while total STAT levels were not reduced upon in vitro IIIB infection of primary human PBMCs, IFN-α-mediated phosphorylation of STAT1 and STAT3 and ISG induction were starkly reduced, with removal of Vif (IIIBΔVif), partially restoring pSTATs, ISG15 and MxB induction. Similarly, pSTAT1 and pSTAT3 expression and IFN-α-induced ISG15 were reduced in PBMCs from HIV-infected patients, compared to healthy controls. Furthermore, IFN-α pre-treatment of a CEM T lymphoblast cells significantly inhibited HIV infection/replication (measured by cellular p24), only in the absence of Vif (IIIBΔVif), but was unable to suppress full length IIIB infection. When analysing the mechanism by which Vif might target the JAK/STAT pathway, we found Vif interacts with both STAT1 and STAT3, (but not STAT2), and its expression promotes ubiquitination and MG132-sensitive, proteosomal degradation of both proteins. Vif's Elongin-Cullin-SOCS-box binding motif enables the formation of an active E3 ligase complex, which we found to be required for Vif's degradation of STAT1 and STAT3. In fact, the E3 ligase scaffold proteins, Cul5 and Rbx2, were also found to be

  2. Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Weijun Zhu

    Full Text Available BACKGROUND: Despite prolonged treatment with highly active antiretroviral therapy (HAART, the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS levels did not reveal any significant changes in the same treatment period. CONCLUSIONS/SIGNIFICANCE: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.

  3. Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication.

    Science.gov (United States)

    Thenin-Houssier, Suzie; de Vera, Ian Mitchelle S; Pedro-Rosa, Laura; Brady, Angela; Richard, Audrey; Konnick, Briana; Opp, Silvana; Buffone, Cindy; Fuhrmann, Jakob; Kota, Smitha; Billack, Blase; Pietka-Ottlik, Magdalena; Tellinghuisen, Timothy; Choe, Hyeryun; Spicer, Timothy; Scampavia, Louis; Diaz-Griffero, Felipe; Kojetin, Douglas J; Valente, Susana T

    2016-04-01

    The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV-1 replication and thus represents an excellent drug target. We developed a high-throughput screening method based on a time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of HIV-1 capsid to identify inhibitors of capsid dimerization. This assay was used to screen a library of pharmacologically active compounds, composed of 1,280in vivo-active drugs, and identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], an organoselenium compound, as an inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of ebselen with the HIV-1 capsid CTD and dimer dissociation when ebselen is in 2-fold molar excess. Electrospray ionization mass spectrometry revealed that ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys198 and Cys218. This compound presents anti-HIV activity in single and multiple rounds of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process. This compound also blocks infection of other retroviruses, such as Moloney murine leukemia virus and simian immunodeficiency virus, but displays no inhibitory activity against hepatitis C and influenza viruses. This study reports the use of TR-FRET screening to successfully identify a novel capsid inhibitor, ebselen, validating HIV-1 capsid as a promising target for drug development. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. An RNA-binding compound that stabilizes the HIV-1 gRNA packaging signal structure and specifically blocks HIV-1 RNA encapsidation.

    Science.gov (United States)

    Ingemarsdotter, Carin K; Zeng, Jingwei; Long, Ziqi; Lever, Andrew M L; Kenyon, Julia C

    2018-03-14

    NSC260594, a quinolinium derivative from the NCI diversity set II compound library, was previously identified in a target-based assay as an inhibitor of the interaction between the HIV-1 (ψ) stem-loop 3 (SL3) RNA and Gag. This compound was shown to exhibit potent antiviral activity. Here, the effects of this compound on individual stages of the viral lifecycle were examined by qRT-PCR, ELISA and Western blot, to see if its actions were specific to the viral packaging stage. The structural effects of NSC260594 binding to the HIV-1 gRNA were also examined by SHAPE and dimerization assays. Treatment of cells with NSC260594 did not reduce the number of integration events of incoming virus, and treatment of virus producing cells did not affect the level of intracellular Gag protein or viral particle release as determined by immunoblot. However, NSC260594 reduced the incorporation of gRNA into virions by up to 82%, without affecting levels of gRNA inside the cell. This reduction in packaging correlated closely with the reduction in infectivity of the released viral particles. To establish the structural effects of NSC260594 on the HIV-1 gRNA, we performed SHAPE analyses to pinpoint RNA structural changes. NSC260594 had a stabilizing effect on the wild type RNA that was not confined to SL3, but that was propagated across the structure. A packaging mutant lacking SL3 did not show this effect. NSC260594 acts as a specific inhibitor of HIV-1 RNA packaging. No other viral functions are affected. Its action involves preventing the interaction of Gag with SL3 by stabilizing this small RNA stem-loop which then leads to stabilization of the global packaging signal region (psi or ψ). This confirms data, previously only shown in analyses of isolated SL3 oligonucleotides, that SL3 is structurally labile in the presence of Gag and that this is critical for the complete psi region to be able to adopt different conformations. Since replication is otherwise unaffected by NSC260594

  5. Vaginal microbiota and its role in HIV transmission and infection.

    Science.gov (United States)

    Petrova, Mariya I; van den Broek, Marianne; Balzarini, Jan; Vanderleyden, Jos; Lebeer, Sarah

    2013-09-01

    The urogenital tract appears to be the only niche of the human body that shows clear differences in microbiota between men and women. The female reproductive tract has special features in terms of immunological organization, an epithelial barrier, microbiota, and influence by sex hormones such as estrogen. While the upper genital tract is regarded as free of microorganisms, the vagina is colonized by bacteria dominated by Lactobacillus species, although their numbers vary considerably during life. Bacterial vaginosis is a common pathology characterized by dysbiosis, which increases the susceptibility for HIV infection and transmission. On the other hand, HIV infections are often characterized by a disturbed vaginal microbiota. The endogenous vaginal microbiota may protect against HIV by direct production of antiviral compounds, through blocking of adhesion and transmission by ligands such as lectins, and/or by stimulation of immune responses. The potential role of probiotics in the prevention of HIV infections and associated symptoms, by introducing them to the vaginal and gastrointestinal tract (GIT), is also discussed. Of note, the GIT is a site of considerable HIV replication and CD4(+) T-cell destruction, resulting in both local and systemic inflammation. Finally, genetically engineered lactobacilli show promise as new microbicidal agents against HIV. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  6. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  7. Preclinical discovery and development of maraviroc for the treatment of HIV.

    Science.gov (United States)

    Veljkovic, Nevena; Vucicevic, Jelica; Tassini, Sabrina; Glisic, Sanja; Veljkovic, Veljko; Radi, Marco

    2015-06-01

    Maraviroc is a first-in-class antiretroviral (ARV) drug acting on a host cell target (CCR5), which blocks the entry of the HIV virus into the cell. Maraviroc is currently indicated for combination ARV treatment in adults infected only with CCR5-tropic HIV-1. This drug discovery case history focuses on the key studies that led to the discovery and approval of maraviroc, as well as on post-launch clinical reports. The article is based on the data reported in published preclinical and clinical studies, conference posters and on drug package data. The profound understanding of HIV's entry mechanisms has provided a strong biological rationale for targeting the chemokine receptor CCR5. The CCR5-antagonist mariviroc, with its unique mode of action and excellent safety profile, is an important therapeutic option for HIV patients. In general, the authors believe that targeting host factors is a useful approach for combating new and re-emerging transmissible diseases, as well as pathogens that easily become resistant to common antiviral drugs. Maraviroc, offering a potent and safe cellular receptor-mediated pharmacological response to HIV, has paved the way for the development of a new generation of host-targeting antivirals.

  8. GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Masayuki; Miguel Salcedo-Gómez, Pedro; Yedidi, Ravikiran S.; Delino, Nicole S.; Nakata, Hirotomo; Venkateswara Rao, Kalapala; Ghosh, Arun K.; Mitsuya, Hiroaki

    2017-09-25

    We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014–0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2ROD. Under the selection condition, where HIV-1NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no variants highly resistant against GRL-09510 emerged over long-term in vitro passage of the virus. Crystallographic analysis demonstrated that the Crwn-THF moiety of GRL-09510 forms strong hydrogen-bond-interactions with HIV-1 protease (PR) active-site amino acids and is bulkier with a larger contact surface, making greater van der Waals contacts with PR than the bis-THF moiety of darunavir. The present data demonstrate that GRL-09510 has favorable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants, that the newly generated P2-Crwn-THF moiety confers highly desirable anti-HIV-1 potency. The use of the novel Crwn-THF moiety sheds lights in the design of novel PIs.

  9. False-negative HIV-1 polymerase chain reaction in a 15-month-old ...

    African Journals Online (AJOL)

    Corresponding author: S Korsman (stephen.korsman@nhls.ac.za). Polymerase chain reaction (PCR) testing is the gold standard for determining the HIV status in children <18 months of age. ... mismatches relative to the consensus are shown as coloured blocks. Nucleic acid numbering relative to consensus C gag p24 is ...

  10. HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

    Directory of Open Access Journals (Sweden)

    Paolo Monini

    Full Text Available Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs. Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.

  11. Influence of common mucosal co-factors on HIV infection in the female genital tract.

    Science.gov (United States)

    Ferreira, Victor H; Kafka, Jessica K; Kaushic, Charu

    2014-06-01

    Women constitute almost half of HIV-infected population globally, and the female genital tract (FGT) accounts for approximately 40% of all new HIV infections worldwide. The FGT is composed of upper and lower parts, distinct in their morphological and functional characteristics. Co-factors in the genital microenvironment, such as presence of hormones, semen, and other sexually transmitted infections, can facilitate or deter HIV infection and play a critical role in determining susceptibility to HIV. In this review, we examine some of these co-factors and their potential influence. Presence of physical and chemical barriers such as epithelial tight junctions, mucus, and anti-microbial peptides can actively block and inhibit viral replication, presenting a significant deterrent to HIV. Upon exposure, HIV and other pathogens first encounter the genital epithelium: cells that express a wide repertoire of pattern recognition receptors that can recognize and directly initiate innate immune responses. These and other interactions in the genital tract can lead to direct and indirect inflammation and enhance the number of local target cells, immune activation, and microbial translocation, all of which promote HIV infection and replication. Better understanding of the dynamics of HIV transmission in the female genital tract would be invaluable for improving the design of prophylactic strategies against HIV. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. CD4- and dynamin-dependent endocytosis of HIV-1 into plasmacytoid dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Pritschet, Kathrin; Donhauser, Norbert; Schuster, Philipp; Ries, Moritz; Haupt, Sabrina; Kittan, Nicolai A.; Korn, Klaus [Institute of Clinical and Molecular Virology, National Reference Centre for Retroviruses, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, 91054 Erlangen (Germany); Poehlmann, Stefan [Institute of Virology, Hannover Medical School, 30625 Hannover (Germany); Holland, Gudrun; Bannert, Norbert [Robert Koch-Institute, Center for Biological Security 4, 13353 Berlin (Germany); Bogner, Elke [Institute of Virology, Charite University Hospital, 10117 Berlin (Germany); Schmidt, Barbara, E-mail: baschmid@viro.med.uni-erlangen.de [Institute of Clinical and Molecular Virology, National Reference Centre for Retroviruses, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, 91054 Erlangen (Germany)

    2012-02-20

    Chronic immune activation, triggered by plasmacytoid dendritic cell (PDC) interferon (IFN)-alpha production, plays an important role in HIV-1 pathogenesis. As the entry of HIV-1 seems to be important for the activation of PDC, we directly characterized the viral entry into these cells using immuno-electron microscopy, cellular fractionation, confocal imaging, and functional experiments. After attachment to PDC, viruses were taken up in an energy-dependent manner. The virions were located in compartments positive for caveolin; early endosomal antigen 1; Rab GTPases 5, 7 and 9; lysosomal-associated membrane protein 1. PDC harbored more virus in endocytic vesicles than CD4+ T cells (p < 0.05). Blocking CD4 inhibited the uptake of virions into cytosolic and endosomal compartments. Dynasore, an inhibitor of dynamin-dependent endocytosis, not the fusion inhibitor T-20, reduced the HIV-1 induced IFN-alpha production. Altogether, our morphological and functional data support the role of endocytosis for the entry and IFN-alpha induction of HIV-1 in PDC.

  13. Crystal structures of HIV-1 nonnucleoside reverse transcriptase inhibitors: N-benzyl-4-methyl-benzimidazoles

    Science.gov (United States)

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

    2009-07-01

    HIV-1 nonnucleoside reverse transcriptase inhibitors are potentially specific and effective drugs in AIDS therapy. The presence of two aromatic systems with an angled orientation in the molecule of the inhibitor is crucial for interactions with HIV-1 RT. The inhibitor drives like a wedge into the cluster of aromatic residues of RT HIV-1 and restrains the enzyme in a conformation that blocks the chemical step of nucleotide incorporation. Structural studies provide useful information for designing new, more active inhibitors. The crystal structures of four NNRTIs are presented here. The investigated compounds are derivatives of N-benzyl-4-methyl-benzimidazole with various aliphatic and aromatic substituents at carbon 2 positions and a 2,6-dihalogeno-substituted N-benzyl moiety. Structural data reported here show that the conformation of the investigated compounds is relatively rigid. Such feature is important for the nonnucleoside inhibitor binding to HIV-1 reverse transcriptase.

  14. Spatial Epidemiology of HIV among Injection Drug Users in Tijuana, Mexico

    Science.gov (United States)

    Brouwer, Kimberly C.; Rusch, Melanie L.; Weeks, John R.; Lozada, Remedios; Vera, Alicia; Magis-Rodríguez, Carlos; Strathdee, Steffanie A.

    2012-01-01

    The northwest border city of Tijuana is Mexico’s fifth largest and is experiencing burgeoning drug use and human immunodeficiency virus (HIV) epidemics. Since local geography influences disease risk, we explored the spatial distribution of HIV among injection drug users (IDUs). From 2006–2007, 1056 IDUs were recruited using respondent-driven sampling, and then followed for eighteen months. Participants underwent semi-annual surveys, mapping, and testing for HIV, tuberculosis, and syphilis. Using Average Nearest Neighbor and Getis-Ord Gi* statistics, locations where participants lived, worked, bought and injected drugs were compared with HIV status and environmental and behavioral factors. Median age was thirty-seven years; 85 percent were male. Females had higher HIV prevalence than males (10.2 percent vs. 3.4 percent; p=0.001). HIV cases at baseline (n=47) most strongly clustered by drug injection sites (Z-Score −6.173; p < 0.001), with a 16 km2 hotspot near the Mexico/U.S. border, encompassing the red-light district. Spatial correlates of HIV included syphilis infection, female gender, younger age, increased hours on the street per day, and higher number of injection partners. Almost all HIV seroconverters injected within a 2.5 block radius of each other immediately prior to seroconversion. Only history of syphilis infection and female gender were strongly associated with HIV in the area where incident cases injected. Directional trends suggested a largely static epidemic until July–December 2008, when HIV spread to the southeast, possibly related to intensified violence and policing that spiked in the latter half of 2008. While clustering allows for targeting interventions, the dynamic nature of epidemics suggests the importance of mobile treatment and harm reduction programs. PMID:23606753

  15. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  16. SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin.

    Science.gov (United States)

    Sun, Wei-Wei; Jiao, Shi; Sun, Li; Zhou, Zhaocai; Jin, Xia; Wang, Jian-Hua

    2018-05-01

    The postintegrational latency of HIV-1 is characterized by reversible silencing of long terminal repeat (LTR)-driven transcription of the HIV genome. It is known that the formation of repressive chromatin at the 5'-LTR of HIV-1 proviral DNA impedes viral transcription by blocking the recruitment of positive transcription factors. How the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. Elucidation of which chromatin reassembly factor mediates the reorganization of chromatin is likely to facilitate the understanding of the host's modulation of HIV-1 transcription and latency. Here we revealed that "Sad1 and UNC84 domain containing 2" (SUN2), an inner nuclear membrane protein, maintained the repressive chromatin and inhibited HIV LTR-driven transcription of proviral DNA through an association with lamin A/C. Specifically, lamin A/C tethered SUN2 to the nucleosomes 1 and 2 of the HIV-1 5'-LTR to block the initiation and elongation of HIV-1 transcription. SUN2 knockdown converted chromatin to an active form and thus enhanced the phosphorylation of RNA polymerase II and its recruitment to the 5'-LTR HIV-1 proviral DNA, leading to reactivation of HIV-1 from latency. Conversely, the exogenous factors such as tumor necrosis factor alpha (TNF-α) induced reactivation, and the replication of HIV-1 led to the disassociation between SUN2 and lamin A/C, suggesting that disruption of the association between SUN2 and lamin A/C to convert the repressive chromatin to the active form might be a prerequisite for the initiation of HIV-1 transcription and replication. Together, our findings indicate that SUN2 is a novel chromatin reassembly factor that helps to maintain chromatin in a repressive state and consequently inhibits HIV-1 transcription. IMPORTANCE Despite the successful use of scores of antiretroviral drugs, HIV latency poses a major impediment to virus eradication. Elucidation of the mechanism of latency facilitates the discovery of new

  17. Induction of HIV neutralizing antibodies against the MPER of the HIV envelope protein by HA/gp41 chimeric protein-based DNA and VLP vaccines.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14 in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy.

  18. Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

    Science.gov (United States)

    Real, Fernando; Sennepin, Alexis; Ganor, Yonatan; Schmitt, Alain; Bomsel, Morgane

    2018-05-08

    During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4 + T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa. Copyright © 2018. Published by Elsevier Inc.

  19. Role of the carbohydrate-binding sites of griffithsin in the prevention of DC-SIGN-mediated capture and transmission of HIV-1.

    Directory of Open Access Journals (Sweden)

    Bart Hoorelbeke

    Full Text Available BACKGROUND: The glycan-targeting C-type DC-SIGN lectin receptor is implicated in the transmission of the human immunodeficiency virus (HIV by binding the virus and transferring the captured HIV-1 to CD4(+ T lymphocytes. Carbohydrate binding agents (CBAs have been reported to block HIV-1 infection. We have now investigated the potent mannose-specific anti-HIV CBA griffithsin (GRFT on its ability to inhibit the capture of HIV-1 to DC-SIGN, its DC-SIGN-directed transmission to CD4(+ T-lymphocytes and the role of the three carbohydrate-binding sites (CBS of GRFT in these processes. FINDINGS: GRFT inhibited HIV-1(IIIB infection of CEM and HIV-1(NL4.3 infection of C8166 CD4(+ T-lymphocytes at an EC50 of 0.059 and 0.444 nM, respectively. The single mutant CBS variants of GRFT (in which a key Asp in one of the CBS was mutated to Ala were about ∼20 to 60-fold less potent to prevent HIV-1 infection and ∼20 to 90-fold less potent to inhibit syncytia formation in co-cultures of persistently HIV-1 infected HuT-78 and uninfected C8166 CD4(+ T-lymphocytes. GRFT prevents DC-SIGN-mediated virus capture and HIV-1 transmission to CD4(+ T-lymphocytes at an EC50 of 1.5 nM and 0.012 nM, respectively. Surface plasmon resonance (SPR studies revealed that wild-type GRFT efficiently blocked the binding between DC-SIGN and immobilized gp120, whereas the point mutant CBS variants of GRFT were ∼10- to 15-fold less efficient. SPR-analysis also demonstrated that wild-type GRFT and its single mutant CBS variants have the capacity to expel bound gp120 from the gp120-DC-SIGN complex in a dose dependent manner, a property that was not observed for HHA, another mannose-specific potent anti-HIV-1 CBA. CONCLUSION: GRFT is inhibitory against HIV gp120 binding to DC-SIGN, efficiently prevents DC-SIGN-mediated transfer of HIV-1 to CD4(+ T-lymphocytes and is able to expel gp120 from the gp120-DC-SIGN complex. Functionally intact CBS of GRFT are important for the optimal action of

  20. Synthetic, structural mimetics of the β-hairpin flap of HIV-1 protease inhibit enzyme function.

    Science.gov (United States)

    Chauhan, Jay; Chen, Shen-En; Fenstermacher, Katherine J; Naser-Tavakolian, Aurash; Reingewertz, Tali; Salmo, Rosene; Lee, Christian; Williams, Emori; Raje, Mithun; Sundberg, Eric; DeStefano, Jeffrey J; Freire, Ernesto; Fletcher, Steven

    2015-11-01

    Small-molecule mimetics of the β-hairpin flap of HIV-1 protease (HIV-1 PR) were designed based on a 1,4-benzodiazepine scaffold as a strategy to interfere with the flap-flap protein-protein interaction, which functions as a gated mechanism to control access to the active site. Michaelis-Menten kinetics suggested our small-molecules are competitive inhibitors, which indicates the mode of inhibition is through binding the active site or sterically blocking access to the active site and preventing flap closure, as designed. More generally, a new bioactive scaffold for HIV-1PR inhibition has been discovered, with the most potent compound inhibiting the protease with a modest K(i) of 11 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Combinatorial Approaches to the Prevention and Treatment of HIV-1 Infection▿†

    Science.gov (United States)

    Pirrone, Vanessa; Thakkar, Nina; Jacobson, Jeffrey M.; Wigdahl, Brian; Krebs, Fred C.

    2011-01-01

    The discovery of the human immunodeficiency virus type 1 (HIV-1) in 1982 soon led to the identification and development of antiviral compounds to be used in treatment strategies for infected patients. Early in the epidemic, drug monotherapies frequently led to treatment failures because the virus quickly developed resistance to the single drug. Following the advent of highly active antiretroviral therapy (HAART) in 1995, dramatic improvements in HIV-1-infected patient health and survival were realized as more refined combination therapies resulted in reductions in viral loads and increases in CD4+ T-cell counts. In the absence of an effective vaccine, prevention of HIV-1 infection has also gained traction as an approach to curbing the pandemic. The development of compounds as safe and effective microbicides has intensified and has focused on blocking the transmission of HIV-1 during all forms of sexual intercourse. Initial preclinical investigations and clinical trials of microbicides focused on single compounds effective against HIV-1. However, the remarkable successes achieved using combination therapy to treat systemic HIV-1 infection have subsequently stimulated the study and development of combination microbicides that will simultaneously inhibit multiple aspects of the HIV-1 transmission process by targeting incoming viral particles, virus-infected cells, and cells susceptible to HIV-1 infection. This review focuses on existing and developing combination therapies, covering preclinical development, in vitro and in vivo efficacy studies, and subsequent clinical trials. The shift in focus within the microbicide development field from single compounds to combination approaches is also explored. PMID:21343462

  2. Gene Therapy of T Helper Cells in HIV Infection. Mathematical Model of the Criteria for Clinical Effect

    DEFF Research Database (Denmark)

    Lund, Ole; Lund, Ole søgaard; Gram, Gregers

    1997-01-01

    The paper presents a mathematical model of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. Our main results are that the therapy should be designed to give the transduced cells a significant but not necessarily total protection against HIV-induced cell...... deaths, and to avoid the production of viral mutants that are insensitive to gene therapy. The transduced cells will not survive if the gene therapy only blocks the spread of virus....

  3. Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

    Directory of Open Access Journals (Sweden)

    Min-Hsuan Lin

    Full Text Available Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1, nucleophosmin (B23 and nucleolin (C23 from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.

  4. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  5. Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway.

    Directory of Open Access Journals (Sweden)

    Juanjuan Zhao

    2018-01-01

    Full Text Available Innate lymphoid cells (ILCs are severely depleted during chronic HIV-1 infection by unclear mechanisms. We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions. Importantly, CD4+ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. Furthermore, chronic HIV-1 infection activated and depleted both CD4+ and CD4- ILC1s, and impaired their cytokine production activity. Highly active antiretroviral (HAART therapy in HIV-1 patients efficiently rescued the ILC1 numbers and reduced their activation, but failed to restore their functionality. We also found that blocking type-I interferon (IFN-I signaling during HIV-1 infection in vivo in humanized mice prevented HIV-1 induced depletion or apoptosis of ILC1 cells. Therefore, we have identified the CD4+ ILC1 cells as a new target population for HIV-1 infection, and revealed that IFN-I contributes to the depletion of ILC1s during HIV-1 infection.

  6. C–C Chemokines Released by Lipopolysaccharide (LPS)-stimulated Human Macrophages Suppress HIV-1 Infection in Both Macrophages and T Cells

    Science.gov (United States)

    Verani, Alessia; Scarlatti, Gabriella; Comar, Manola; Tresoldi, Eleonora; Polo, Simona; Giacca, Mauro; Lusso, Paolo; Siccardi, Antonio G.; Vercelli, Donata

    1997-01-01

    Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C–C chemokines (RANTES, MIP-1α, and MIP-1β) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C–C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C–C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes. PMID:9120386

  7. IMPORTANCE OF MULTIPLE CRITERIA FOR PRIORITY SETTING OF HIV/AIDS INTERVENTIONS.

    Science.gov (United States)

    Tromp, Noor; Prawiranegara, Rozar; Siregar, Adiatma; Sunjaya, Deni; Baltussen, Rob

    2015-01-01

    This study describes the views of various stakeholders on the importance of different criteria for priority setting of HIV/AIDS interventions in Indonesia. Based on a general list of criteria and a focus group discussion with stakeholders (n = 6), a list was developed of thirty-two criteria that play a role in priority setting in HIV/AIDS control in West-Java province. Criteria were categorized according to the World Health Organization's health system goals and building block frameworks. People living with HIV/AIDS (n = 49), healthcare workers (HCW) (n = 41), the general population (n = 43), and policy makers (n = 22) rated the importance of thirty-two criteria on a 5-point Likert-scale. Thereafter, respondents ranked the highest rated criteria to express more detailed preferences. Stakeholders valued the following criteria as most important for the priority setting of HIV/AIDS interventions: an intervention's impact on the HIV/AIDS epidemic, reduction of stigma, quality of care, effectiveness on individual level, and feasibility in terms of current capacity of the health system (i.e., HCW, product, information, and service requirements), financial sustainability, and acceptance by donors. Overall, stakeholders' preferences for the importance of criteria are similar. Our study design outlines an approach for other settings to identify which criteria are important for priority setting of health interventions. For Indonesia, these study results may be used in priority setting processes for HIV/AIDS control and may contribute to more transparent and systematic allocation of resources.

  8. Analysis of Block OMP using Block RIP

    OpenAIRE

    Wang, Jun; Li, Gang; Zhang, Hao; Wang, Xiqin

    2011-01-01

    Orthogonal matching pursuit (OMP) is a canonical greedy algorithm for sparse signal reconstruction. When the signal of interest is block sparse, i.e., it has nonzero coefficients occurring in clusters, the block version of OMP algorithm (i.e., Block OMP) outperforms the conventional OMP. In this paper, we demonstrate that a new notion of block restricted isometry property (Block RIP), which is less stringent than standard restricted isometry property (RIP), can be used for a very straightforw...

  9. Specific assay measuring binding of /sup 125/I-Gp 120 from HIV to T4/sup +//CD4/sup +/ cells

    Energy Technology Data Exchange (ETDEWEB)

    Lundin, K.; Nygren, A.; Ramstedt, U.; Gidlund, M.; Wigzell, H.; Arthur, L.O.; Robey, W.G.; Morein, B.

    1987-02-26

    The HIV (HTLV-III) envelope glycoprotein, Gp120, was isolated from virus-infected tissue culture cells using affinity chromatography. A radioimmunoassay was developed to determine the degree of iodinated Gp120 to target CD4/sup +/ (T4/sup +/) cells. /sup 125/I-Gp120 could be shown to selectively bind to CD4/sup +/ cells only. The Gp120 remained bound to these cells after repeated washes. Monoclonal anti-CD4 antibodies block the binding of Gp120 to CD4/sup +/ cells. Monoclonal antibodies to other cell surface components do not interfere with /sup 125/I-Gp120 binding. All IgG antibodies from HIV seropositive donors tested block /sup 125/I-GP120 binding, though with variable titers. The authors believe that this assay provides further proof for the use of CD4 (T4) as a component of the receptor for HIV. It represents a safe, objective and sensitive method for the analysis of Gp120-CD4 interactions, as well as the potential of antibodies to interfere with this binding. (Auth.). 24 refs.; 2 figs.; 8 tabs.

  10. Synthesis of a Vpr-Binding Derivative for Use as a Novel HIV-1 Inhibitor.

    Science.gov (United States)

    Hagiwara, Kyoji; Ishii, Hideki; Murakami, Tomoyuki; Takeshima, Shin-nosuke; Chutiwitoonchai, Nopporn; Kodama, Eiichi N; Kawaji, Kumi; Kondoh, Yasumitsu; Honda, Kaori; Osada, Hiroyuki; Tsunetsugu-Yokota, Yasuko; Suzuki, Masaaki; Aida, Yoko

    2015-01-01

    The emergence of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus type 1 (HIV-1) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. We previously identified a potential parent compound, hematoxylin, which suppresses the nuclear import of HIV-1 via the Vpr-importin α interaction and inhibits HIV-1 replication in a Vpr-dependent manner by blocking nuclear import of the pre-integration complex. However, it was unstable. Here, we synthesized a stable derivative of hematoxylin that bound specifically and stably to Vpr and inhibited HIV-1 replication in macrophages. Furthermore, like hematoxylin, the derivative inhibited nuclear import of Vpr in an in vitro nuclear import assay, but had no effect on Vpr-induced G2/M phase cell cycle arrest or caspase activity. Interestingly, this derivative bound strongly to amino acid residues 54-74 within the C-terminal α-helical domain (αH3) of Vpr. These residues are highly conserved among different HIV strains, indicating that this region is a potential target for drug-resistant HIV-1 infection. Thus, we succeeded in developing a stable hematoxylin derivative that bound directly to Vpr, suggesting that specific inhibitors of the interaction between cells and viral accessory proteins may provide a new strategy for the treatment of HIV-1 infection.

  11. Synthesis of a Vpr-Binding Derivative for Use as a Novel HIV-1 Inhibitor.

    Directory of Open Access Journals (Sweden)

    Kyoji Hagiwara

    Full Text Available The emergence of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus type 1 (HIV-1 therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. We previously identified a potential parent compound, hematoxylin, which suppresses the nuclear import of HIV-1 via the Vpr-importin α interaction and inhibits HIV-1 replication in a Vpr-dependent manner by blocking nuclear import of the pre-integration complex. However, it was unstable. Here, we synthesized a stable derivative of hematoxylin that bound specifically and stably to Vpr and inhibited HIV-1 replication in macrophages. Furthermore, like hematoxylin, the derivative inhibited nuclear import of Vpr in an in vitro nuclear import assay, but had no effect on Vpr-induced G2/M phase cell cycle arrest or caspase activity. Interestingly, this derivative bound strongly to amino acid residues 54-74 within the C-terminal α-helical domain (αH3 of Vpr. These residues are highly conserved among different HIV strains, indicating that this region is a potential target for drug-resistant HIV-1 infection. Thus, we succeeded in developing a stable hematoxylin derivative that bound directly to Vpr, suggesting that specific inhibitors of the interaction between cells and viral accessory proteins may provide a new strategy for the treatment of HIV-1 infection.

  12. 31 CFR 595.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions § 595.301 Blocked account; blocked property. The terms blocked account and blocked...

  13. Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1

    International Nuclear Information System (INIS)

    Diaz-Griffero, Felipe; Vandegraaff, Nick; Li Yuan; McGee-Estrada, Kathleen; Stremlau, Matthew; Welikala, Sohanya; Si Zhihai; Engelman, Alan; Sodroski, Joseph

    2006-01-01

    In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5α with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain

  14. Binding of recombinant HIV coat protein gp120 to human monocytes

    International Nuclear Information System (INIS)

    Finbloom, D.S.; Hoover, D.L.; Meltzer, M.S.

    1991-01-01

    Inasmuch as the exact level of CD4 Ag expression on macrophages is controversial and because HIV may interact with macrophages in a manner different from that on T cells, we analyzed the binding of gp120 to freshly isolated and cultured monocytes. rgp120 was iodinated using the lactoperoxidase method to a sp. act. of 600 Ci/mmol. Highly purified monocytes (greater than 90%) were isolated from the leukapheresed blood of normal volunteers by Ficoll-Hypaque sedimentation followed by countercurrent centrifugal elutriation and cultured 7 days in DMEM supplemented with 1000 U/ml macrophage CSF in 10% human serum. Whereas MOLT/4 cells consistently bound freshly prepared 125I-rgp120 at 80% specificity with 5100 +/- 700 mol/cell, MCSF cultured monocytes bound rgp120 at only 0 to 20% specificity and 420 +/- 200 mol/cell. Most of the radioactivity bound by these cells could not be blocked by the addition of unlabeled rgp120. In contrast, the U937 myeloid cell line bound rgp120 with 50% specificity and about 2500 mol/cell. Whereas the antibody OKT4a (anti-CD4) blocked 80% of the binding on MOLT/4 cells and 50% on U937 cells, binding was only inhibited on the average of 6% on cultured monocytes. When soluble rCD4 was used as an inhibitor, binding to MOLT/4 cells was blocked by 80%. In contrast, binding to cultured monocytes was inhibited by 28%. HIV infectivity was blocked by similar concentrations of OKT4a. These observations suggest that although most binding of gp120 to cultured monocytes is not to the CD4 determinant, several hundred molecules do bind to a CD4-like molecule which promotes virus entry and replication

  15. Nerve Blocks

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Nerve Blocks A nerve block is an injection to ... the limitations of Nerve Block? What is a Nerve Block? A nerve block is an anesthetic and/ ...

  16. Dominican Children with HIV Not Receiving Antiretrovirals: Massage Therapy Influences their Behavior and Development

    Directory of Open Access Journals (Sweden)

    Maria Hernandez-Reif

    2008-01-01

    Full Text Available Forty-eight children (M age = 4.8 years infected with HIV/AIDS and living in the Dominican Republic were randomly assigned to a massage therapy or a play session control group. The children in the massage therapy group received two weekly 20-min massages for 12 weeks; the children in the control group participated in a play session (coloring, playing with blocks for the same duration and length as the massage therapy group. Overall, the children in the massage therapy group improved in self-help abilities and communication, suggesting that massage therapy may enhance daily functioning for children with HIV/AIDS. Moreover, the HIV infected children who were six or older also showed a decrease in internalizing behaviors; specifically depressive/anxious behaviors and negative thoughts were reduced. Additionally, baseline assessments revealed IQ equivalence below normal functioning for 70% of the HIV infected children and very high incidences of mood problems (depression, withdrawn for 40% of the children and anxiety problems for 20% of the children, suggesting the need for better monitoring and alternative interventions in countries with limited resources to improve cognition and the mental health status of children infected with HIV/AIDS.

  17. Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2002-11-01

    Full Text Available Abstract Background Cellulose acetate phthalate (CAP in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH Methods Enzyme linked immunosorbent assays (ELISA were used to (1 study HIV-1 IIIB and BaL binding to micronized CAP; (2 detect virus disintegration; and (3 measure gp41 six-helix bundle formation. Cells containing integrated HIV-1 LTR linked to the β-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity. Results 1 HIV-1 IIIB and BaL, respectively, effectively bound to micronized CAP. 2 The interaction between HIV-1 and micronized CAP led to: (a gp41 six-helix bundle formation; (b virus disintegration and shedding of envelope glycoproteins; and (c rapid loss of infectivity. Polymers other than CAP, except Carbomer 974P, elicited gp41 six-helix bundle formation in HIV-1 IIIB but only poly(napthalene sulfonate, in addition to CAP, had this effect on HIV-1 BaL. These polymers differed with respect to their virucidal activities, the differences being more pronounced for HIV-1 BaL. Conclusions Micronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.

  18. The Roles of Behavioral and Social Science Research in the Fight Against HIV/AIDS: A Functional Framework.

    Science.gov (United States)

    Gaist, Paul; Stirratt, Michael J

    2017-08-01

    Landmark advances have been made in HIV/AIDS prevention and treatment. These include proof-of-concept and public health implementation of preexposure prophylaxis and "treatment as prevention" to reduce HIV transmission as well as definitive evidence of the clinical gain from early antiretroviral treatment initiation. Significant progress has been made in understanding and addressing the social contexts and behavioral factors that impact HIV prevention, care, and treatment interventions. These include facilitating uptake of testing and counseling, developing technology-based interventions that increase viral suppression, reducing HIV/AIDS-related stigma, and addressing other sociobehavioral and structural barriers to care and treatment. This evolving landscape provides an important juncture to assess current and future directions for HIV/AIDS behavioral and social science research (BSSR). We propose a functional framework for HIV/AIDS-related BSSR, highlighting 4 primary BSSR domains: (1) understanding vulnerable populations and contexts of risk ("Basic BSSR"); (2) improving behavioral and social factor approaches to risk reduction, prevention, and care ("Elemental BSSR"); (3) strengthening the design and outcomes of biomedically focused research in HIV/AIDS treatment and prevention ("Supportive BSSR"); and (4) contributing building blocks to integrated HIV/AIDS prevention and treatment approaches ("Integrative BSSR"). These domains and their resulting confluence at the highest level underscore how fundamental and essential BSSR is to current and future efforts to prevent, treat, and cure HIV/AIDS.

  19. A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Anthony M. [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Cheung, Pamela [Integrated Screening Core, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Swartz, Talia H.; Li, Hongru [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Tsibane, Tshidi [Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Durham, Natasha D. [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States); Basler, Christopher F. [Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Felsenfeld, Dan P. [Integrated Screening Core, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Chen, Benjamin K., E-mail: benjamin.chen@mssm.edu [Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY (United States)

    2016-03-15

    Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.

  20. A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry

    International Nuclear Information System (INIS)

    Esposito, Anthony M.; Cheung, Pamela; Swartz, Talia H.; Li, Hongru; Tsibane, Tshidi; Durham, Natasha D.; Basler, Christopher F.; Felsenfeld, Dan P.; Chen, Benjamin K.

    2016-01-01

    Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors that block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.

  1. Up-regulation of the Neuronal Nicotinic Receptor α7 by HIV Glycoprotein 120

    Science.gov (United States)

    Ballester, Leomar Y.; Capó-Vélez, Coral M.; García-Beltrán, Wilfredo F.; Ramos, Félix M.; Vázquez-Rosa, Edwin; Ríos, Raymond; Mercado, José R.; Meléndez, Roberto I.; Lasalde-Dominicci, José A.

    2012-01-01

    Approximately 30–50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and the molecular mechanisms behind HIV-associated neurocognitive decline are not understood. There are several hypotheses to explain the development of dementia in HIV+ individuals, including neuroinflammation mediated by infected microglia and neuronal toxicity by HIV proteins. A key protein associated with the neurological complications of HIV, gp120, forms part of the viral envelope and can be found in the CSF of infected individuals. HIV-1-gp120 interacts with several receptors including CD4, CCR5, CXCR4, and nicotinic acetylcholine receptors (nAChRs). However, the role of nAChRs in HIV-associated neurocognitive disorder has not been investigated. We studied the effects of gp120IIIB on the expression and function of the nicotinic receptor α7 (α7-nAChR). Our results show that gp120, through activation of the CXCR4 chemokine receptor, induces a functional up-regulation of α7-nAChRs. Because α7-nAChRs have a high permeability to Ca2+, we performed TUNEL staining to investigate the effects of receptor up-regulation on cell viability. Our data revealed an increase in cell death, which was blocked by the selective antagonist α-bungarotoxin. The in vitro data are supported by RT-PCR and Western blot analysis, confirming a remarkable up-regulation of the α7-nAChR in gp120-transgenic mice brains. Specifically, α7-nAChR up-regulation is observed in mouse striatum, a region severely affected in HIV+ patients. In summary, CXCR4 activation induces up-regulation of α7-nAChR, causing cell death, suggesting that α7-nAChR is a previously unrecognized contributor to the neurotoxicity associated with HIV infection. PMID:22084248

  2. Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle.

    Science.gov (United States)

    Smith, Johanna A; Daniel, Rene

    2016-11-13

    Vaginal transmission is crucial to the spread of HIV-1 around the world. It is not yet clear what type (s) of innate defenses against HIV-1 infection are present in the vagina. Here, we aimed to determine whether human vaginal fluid contains exosomes that may possess anti-HIV-1 activity. The exosomal fraction was isolated from samples of vaginal fluids. The presence of exosomes was confirmed by flow cytometry and western blotting. The newly discovered exosomes were tested for their ability to block early steps of HIV-1 infection in vitro using established cell culture systems and real time PCR-based methods. Vaginal fluid contains exosomes expressing CD9, CD63, and CD81 exosomal markers. The exosomal fraction of the fluid-reduced transmission of HIV-1 vectors by 60%, the efficiency of reverse transcription step by 58.4%, and the efficiency of integration by 47%. Exosomes had no effect on the entry of HIV-1 vectors. Human vaginal fluid exosomes are newly discovered female innate defenses that may protect women against HIV-1 infection.

  3. Decreased HIV diversity after allogeneic stem cell transplantation of an HIV-1 infected patient: a case report

    Directory of Open Access Journals (Sweden)

    Thielen Alexander

    2010-03-01

    Full Text Available Abstract The human immunodeficiency virus type 1 (HIV-1 coreceptor use and viral evolution were analyzed in blood samples from an HIV-1 infected patient undergoing allogeneic stem cell transplantation (SCT. Coreceptor use was predicted in silico from sequence data obtained from the third variable loop region of the viral envelope gene with two software tools. Viral diversity and evolution was evaluated on the same samples by Bayesian inference and maximum likelihood methods. In addition, phenotypic analysis was done by comparison of viral growth in peripheral blood mononuclear cells and in a CCR5 (R5-deficient T-cell line which was controlled by a reporter assay confirming viral tropism. In silico coreceptor predictions did not match experimental determinations that showed a consistent R5 tropism. Anti-HIV directed antibodies could be detected before and after the SCT. These preexisting antibodies did not prevent viral rebound after the interruption of antiretroviral therapy during the SCT. Eventually, transplantation and readministration of anti-retroviral drugs lead to sustained increase in CD4 counts and decreased viral load to undetectable levels. Unexpectedly, viral diversity decreased after successful SCT. Our data evidence that only R5-tropic virus was found in the patient before and after transplantation. Therefore, blocking CCR5 receptor during stem cell transplantation might have had beneficial effects and this might apply to more patients undergoing allogeneic stem cell transplantation. Furthermore, we revealed a scenario of HIV-1 dynamic different from the commonly described ones. Analysis of viral evolution shows the decrease of viral diversity even during episodes with bursts in viral load.

  4. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  5. NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site.

    Directory of Open Access Journals (Sweden)

    Shahin Ranjbar

    2006-12-01

    Full Text Available To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5, which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS.

  6. Glycosylphosphatidylinositol-Anchored Anti-HIV scFv Efficiently Protects CD4 T Cells from HIV-1 Infection and Deletion in hu-PBL Mice

    Science.gov (United States)

    Ye, Chaobaihui; Wang, Weiming; Cheng, Liang; Li, Guangming; Wen, Michael; Wang, Qi; Zhang, Qing; Li, Dan

    2016-01-01

    ABSTRACT Despite success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of the HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from a homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance in permissive cells. Here, we employed a glycosylphosphatidylinositol (GPI)-scFv X5 approach to confer resistance of human primary CD4 T cells to HIV-1. We showed that primary CD4 T cells expressing GPI-scFv X5 were resistant to CCR5 (R5)-, CXCR4 (X4)-, and dual-tropic HIV-1 and had a survival advantage compared to control cells ex vivo. In a hu-PBL mouse study, GPI-scFv X5-transduced CD4 T cells were selected in peripheral blood and lymphoid tissues upon HIV-1 infection. Finally, GPI-scFv X5-transduced CD4 T cells, after being cotransfused with HIV-infected cells, showed significantly reduced viral loads and viral RNA copy numbers relative to CD4 cells in hu-PBL mice compared to mice with GPI-scFv AB65-transduced CD4 T cells. We conclude that GPI-scFv X5-modified CD4 T cells could potentially be used as a genetic intervention against both R5- and X4-tropic HIV-1 infections. IMPORTANCE Blocking of HIV-1 entry is one of most promising approaches for therapy. Genetic disruption of the HIV-1 coreceptor CCR5 by nucleases in T cells is under 2 clinical trials and leads to reduced viremia in patients. However, the emergence of viruses using the CXCR4 coreceptor is a concern for therapies applying single-coreceptor disruption. Here, we report that HIV-1-permissive CD4 T cells engineered with GPI-scFv X5 are resistant to R5-, X4-, or dual-tropic virus infection ex vivo. In a preclinical study using hu-PBL mice, we show that CD4 T cells were protected and that GPI-scFv X5

  7. Testing block subdivision algorithms on block designs

    Science.gov (United States)

    Wiseman, Natalie; Patterson, Zachary

    2016-01-01

    Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

  8. Serodiagnostic profiles of HIV and HIV pathogenesis in vivo

    NARCIS (Netherlands)

    Goudsmit, J.; Lange, J. M.; Smit, L.; Bakker, M.; Klaver, B.; Danner, S. A.; Coutinho, R. A.

    1988-01-01

    Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies, formation of antigen/antibody complexes and clearance of such complexes. Transient HIV antigenemia appearing generally 6-8 weeks prior to HIV antibody (HIV-Ab) seroconversion and lasting 3-4 months

  9. Recombinant protein of heptad-repeat HR212, a stable fusion inhibitor with potent anti-HIV action in vitro

    International Nuclear Information System (INIS)

    Pang, Wei; Wang Ruirui; Yang Liumeng; Liu Changmei; Tien Po; Zheng Yongtang

    2008-01-01

    HR212, a recombinant protein expressed in Escherichia coli, has been previously reported to inhibit HIV-1 membrane fusion at low nanomolar level. Here we report that HR212 is effective in blocking laboratory strain HIV-1 IIIB entry and replication with EC 50 values of 3.92 ± 0.62 and 6.59 ± 1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1 KM018 with EC 50 values of 44.44 ± 10.20 nM, as well as suppressing HIV-1-induced cytopathic effect with an EC 50 value of 3.04 ± 1.20 nM. It also inhibited HIV-2 ROD and HIV-2 CBL-20 entry and replication in the μM range. Notably, HR212 was highly effective against T20-resistant strains with EC 50 values ranging from 5.09 to 7.75 nM. Unlike T20, HR212 showed stability sufficient to inhibit syncytia formation in a time-of-addition assay, and was insensitive to proteinase K digestion. These results suggest that HR212 has great potential to be further developed as novel HIV-1 fusion inhibitor for treatment of HIV/AIDS patients, particularly for those infected by T20-resistant variants

  10. Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

    Science.gov (United States)

    Vasylyeva, Tetyana I; Friedman, Samuel R; Lourenco, Jose; Gupta, Sunetra; Hatzakis, Angelos; Pybus, Oliver G; Katzourakis, Aris; Smyrnov, Pavlo; Karamitros, Timokratis; Paraskevis, Dimitrios; Magiorkinis, Gkikas

    2016-11-28

    Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post-first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.

  11. Side Effects of HIV Medicines: HIV and Diabetes

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... throughout the body. A hormone called insulin helps move the glucose into the cells. Once in the ...

  12. Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist Reveals Mechanisms of Chemokine Recognition and Molecular Mimicry by HIV

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yi; Han, Gye Won; Abagyan, Ruben; Wu, Beili; Stevens, Raymond C.; Cherezov, Vadim; Kufareva, Irina; Handel, Tracy M. (USC); (Chinese Aca. Sci.); (UCSD)

    2017-06-01

    CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc. Molecular modeling indicated that HIV gp120 mimicked the chemokine interaction with CCR5, providing an explanation for the ability of CCR5 to recognize diverse ligands and gp120 variants. Our findings reveal that structural plasticity facilitates receptor-chemokine specificity and enables exploitation by HIV, and provide insight into the design of small molecule and protein inhibitors for HIV and other CCR5-mediated diseases.

  13. The role of culture in effective HIV/AIDS communication by theatre in South Africa.

    Science.gov (United States)

    Uwah, Chijioke

    2013-01-01

    The need to effectively communicate HIV/AIDS messages in South Africa, given the high prevalence of the pandemic, cannot be overemphasised. Communication scholars have long emphasised the need to recognise adherence to cultural norms of target communities as catalyst for effective HIV/AIDS communication. Unfortunately this call has not been totally heeded by the designers of HIV/AIDS communication instruments. In the case of theatre, research has shown that in South Africa, theatre groups have gone into communities with pre-packaged plays without due cognisance of the cultural norms and beliefs of the target population. This research was conducted in KwaZulu-Natal (the province with the highest prevalence rate of HIV/AIDS infection in South Africa). Using a qualitative research methodology this paper investigated the inclusion/non-inclusion of the cultural norms of the target population in the design of the dramatic performance by the theatre group in its HIV/AIDS campaigns. The findings indicate that while the group did try to incorporate aspects of the cultural norms of the target population, it did so at a level that failed to effectively communicate the HIV/AIDS message to its audiences. This paper therefore seeks to show through empirical evidence that the non-inclusion of cultural norms and values of the target population has acted as a stumbling block in the effective communication of HIV/AIDS messages by theatre groups in the country.

  14. Correlates of HIV stigma in HIV-positive women.

    Science.gov (United States)

    Wagner, Anne C; Hart, Trevor A; Mohammed, Saira; Ivanova, Elena; Wong, Joanna; Loutfy, Mona R

    2010-06-01

    We examined the variables associated with HIV stigma in HIV-positive women currently living in Ontario, Canada. Based on previous literature, we predicted that variables of social marginalization (e.g., ethnicity, income, education), medical variables (e.g., higher CD4 count, lower viral load), and increased psychological distress would be associated with higher perceived HIV stigma among HIV-positive women. One hundred fifty-nine HIV-positive women between the ages of 18 and 52 in Ontario completed self-report measures of the aforementioned variables. Women were recruited through 28 AIDS service organizations, eight HIV clinics, and two community health centers. In multiple regression analyses, for women born in Canada, lower educational level and higher anxiety were associated with higher HIV stigma. For women born outside of Canada, having been judged by a physician in Canada for trying to become pregnant was associated with higher HIV stigma. For HIV-positive women born outside of Canada, negative judgment by a physician regarding intentions to become pregnant should be addressed to reduce perceived HIV stigma and vice versa. Health care providers should be trained in the provision of sensitive and effective health care for women living with HIV, especially when providing reproductive health care.

  15. Medicinal chemistry of small molecule CCR5 antagonists for blocking HIV-1 entry: a review of structural evolution.

    Science.gov (United States)

    Tian, Ye; Zhang, Dujuan; Zhan, Peng; Liu, Xinyong

    2014-01-01

    CCR5, a member of G protein-coupled receptors superfamily, plays an important role in the HIV-1 entry process. Antagonism of this receptor finally leads to the inhibition of R5 strains of HIV entry into the human cells. The identification of CCR5 antagonists as antiviral agents will provide more option for HAART. Now, more than a decade after the first small molecule CCR5 inhibitor was discovered, great achievements have been made. In this article, we will give a brief introduction of several series of small molecule CCR5 antagonists, focused on their appealing structure evolution, essential SAR information and thereof the enlightenment of strategies on CCR5 inhibitors design.

  16. HIV Testing

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... All Collapse All Should I get tested for HIV? CDC recommends that everyone between the ages of ...

  17. Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1-infected CD4+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ting Pan

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD, indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1, a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

  18. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

    International Nuclear Information System (INIS)

    Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie

    2007-01-01

    Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767 stop , which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752 N750K ) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752 N750K exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses

  19. Cutaneous Sensory Block Area, Muscle-Relaxing Effect, and Block Duration of the Transversus Abdominis Plane Block

    DEFF Research Database (Denmark)

    Støving, Kion; Rothe, Christian; Rosenstock, Charlotte V

    2015-01-01

    BACKGROUND AND OBJECTIVES: The transversus abdominis plane (TAP) block is a widely used nerve block. However, basic block characteristics are poorly described. The purpose of this study was to assess the cutaneous sensory block area, muscle-relaxing effect, and block duration. METHODS: Sixteen...... healthy volunteers were randomized to receive an ultrasound-guided unilateral TAP block with 20 mL 7.5 mg/mL ropivacaine and placebo on the contralateral side. Measurements were performed at baseline and 90 minutes after performing the block. Cutaneous sensory block area was mapped and separated...... into a medial and lateral part by a vertical line through the anterior superior iliac spine. We measured muscle thickness of the 3 lateral abdominal muscle layers with ultrasound in the relaxed state and during maximal voluntary muscle contraction. The volunteers reported the duration of the sensory block...

  20. Care of HIV-exposed and HIV-infected neonates

    African Journals Online (AJOL)

    However, further reduction in MTCT may be possible if newborns at high risk of acquiring HIV ... infants of breastfeeding mothers with newly diagnosed HIV infection, dual NVP/ .... birth HIV DNA PCR testing for HIV-exposed low birth weight.

  1. Acute HIV Discovered During Routine HIV Screening With HIV Antigen-Antibody Combination Tests in 9 US Emergency Departments.

    Science.gov (United States)

    White, Douglas A E; Giordano, Thomas P; Pasalar, Siavash; Jacobson, Kathleen R; Glick, Nancy R; Sha, Beverly E; Mammen, Priya E; Hunt, Bijou R; Todorovic, Tamara; Moreno-Walton, Lisa; Adomolga, Vincent; Feaster, Daniel J; Branson, Bernard M

    2018-01-05

    Newer combination HIV antigen-antibody tests allow detection of HIV sooner after infection than previous antibody-only immunoassays because, in addition to HIV-1 and -2 antibodies, they detect the HIV-1 p24 antigen, which appears before antibodies develop. We determine the yield of screening with HIV antigen-antibody tests and clinical presentations for new diagnoses of acute and established HIV infection across US emergency departments (EDs). This was a retrospective study of 9 EDs in 6 cities with HIV screening programs that integrated laboratory-based antigen-antibody tests between November 1, 2012, and December 31, 2015. Unique patients with newly diagnosed HIV infection were identified and classified as having either acute HIV infection or established HIV infection. Acute HIV infection was defined as a repeatedly reactive antigen-antibody test result, a negative HIV-1/HIV-2 antibody differentiation assay, or Western blot result, but detectable HIV ribonucleic acid (RNA); established HIV infection was defined as a repeatedly reactive antigen-antibody test result and a positive HIV-1/HIV-2 antibody differentiation assay or Western blot result. The primary outcomes were the number of new HIV diagnoses and proportion of patients with laboratory-defined acute HIV infection. Secondary outcomes compared reason for visit and the clinical presentation of acute HIV infection. In total, 214,524 patients were screened for HIV and 839 (0.4%) received a new diagnosis, of which 122 (14.5%) were acute HIV infection and 717 (85.5%) were established HIV infection. Compared with patients with established HIV infection, those with acute HIV infection were younger, had higher RNA and CD4 counts, and were more likely to have viral syndrome (41.8% versus 6.5%) or fever (14.3% versus 3.4%) as their reason for visit. Most patients with acute HIV infection displayed symptoms attributable to acute infection (median symptom count 5 [interquartile range 3 to 6]), with fever often

  2. 31 CFR 594.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions § 594.301 Blocked account; blocked property. The terms blocked account and...

  3. HIV and drug abuse mediate astrocyte senescence in a β-catenin-dependent manner leading to neuronal toxicity.

    Science.gov (United States)

    Yu, Chunjiang; Narasipura, Srinivas D; Richards, Maureen H; Hu, Xiu-Ti; Yamamoto, Bryan; Al-Harthi, Lena

    2017-10-01

    Emerging evidence suggests that cell senescence plays an important role in aging-associated diseases including neurodegenerative diseases. HIV leads to a spectrum of neurologic diseases collectively termed HIV-associated neurocognitive disorders (HAND). Drug abuse, particularly methamphetamine (meth), is a frequently abused psychostimulant among HIV+ individuals and its abuse exacerbates HAND. The mechanism by which HIV and meth lead to brain cell dysregulation is not entirely clear. In this study, we evaluated the impact of HIV and meth on astrocyte senescence using in vitro and several animal models. Astrocytes constitute up to 50% of brain cells and play a pivotal role in marinating brain homeostasis. We show here that HIV and meth induce significant senescence of primary human fetal astrocytes, as evaluated by induction of senescence markers (β-galactosidase and p16 INK 4A ), senescence-associated morphologic changes, and cell cycle arrest. HIV- and meth-mediated astrocyte senescence was also demonstrated in three small animal models (humanized mouse model of HIV/NSG-huPBMCs, HIV-transgenic rats, and in a meth administration rat model). Senescent astrocytes in turn mediated neuronal toxicity. Further, we show that β-catenin, a pro-survival/proliferation transcriptional co-activator, is downregulated by HIV and meth in human astrocytes and this downregulation promotes astrocyte senescence while induction of β-catenin blocks HIV- and meth-mediated astrocyte senescence. These studies, for the first time, demonstrate that HIV and meth induce astrocyte senescence and implicate the β-catenin pathway as potential therapeutic target to overcome astrocyte senescence. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  4. Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

    Directory of Open Access Journals (Sweden)

    Dobson Wendy

    2011-06-01

    Full Text Available Abstract Background RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK family of SR protein kinases on HIV-1 expression and RNA processing was examined. Results Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication. Conclusions Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

  5. Affective differences in Iowa Gambling Task performance associated with sexual risk taking and substance use among HIV-positive and HIV-negative men who have sex with men

    Science.gov (United States)

    Golub, Sarit A.; Thompson, Louisa I.; Kowalczyk, William J.

    2016-01-01

    We investigated the relationship between emotional distress and decision-making in sexual risk and substance use behavior among 174 (ages 25 to 50, 53% black) men who have sex with men (MSM), a population at increased risk for HIV. The sample was stratified by HIV status. Measures of affective decision-making (Iowa Gambling Task, IGT, Bechara et al., 1994), depression, anxiety, sex acts, and substance use during the past 60 days were collected at our research center. Negative binomial regression models were used to examine the relationship between age, HIV status, anxiety, depression, and IGT performance in the prediction of number of risky sex acts and substance use days. Among those without anxiety or depression, both number of risky sex acts and drug use days decreased with better performance during risky trials (i.e., last two blocks) of the IGT. For those with higher rates of anxiety, but not depression, IGT risk trial performance and risky sex acts increased concomitantly. Anxiety also interacted with IGT performance across all trials to predict substance use, such that anxiety was associated with greater substance use among those with better IGT performance. The opposite was true for those with depression, but only during risk trials. HIV-positive participants reported fewer substance use days than HIV-negative participants, but there was no difference in association between behavior and IGT performance by HIV status. Our findings suggest that anxiety may exacerbate risk-taking behavior when affective decision-making ability is intact. The relationship between affective decision-making and risk taking may be sensitive to different profiles of emotional distress, as well as behavioral context. Investigations of affective decision-making in sexual risk taking and substance use should examine different distress profiles separately, with implications for HIV prevention efforts. PMID:26745769

  6. Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene.

    Science.gov (United States)

    Chan, Chi N; Trinité, Benjamin; Levy, David N

    2017-09-01

    HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health-promoting benefits. Resveratrol has been shown to inhibit the replication of several viruses, including herpes simplex viruses 1 and 2, papillomaviruses, severe acute respiratory syndrome virus, and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at a low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, an HIV-1 and simian immunodeficiency virus protein that increases deoxynucleoside triphosphate (dNTP) levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene, or related compounds as adjuvants in anti-HIV preexposure prophylaxis (PrEP) formulations. Copyright © 2017 American Society for Microbiology.

  7. HIV/AIDS

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most ...

  8. ["Habitual" left branch block alternating with 2 "disguised" bracnch block].

    Science.gov (United States)

    Lévy, S; Jullien, G; Mathieu, P; Mostefa, S; Gérard, R

    1976-10-01

    Two cases of alternating left bundle branch block and "masquerading block" (with left bundle branch morphology in the stnadard leads and right bundle branch block morphology in the precordial leads) were studied by serial tracings and his bundle electrocardiography. In case 1 "the masquerading" block was associated with a first degree AV block related to a prolongation of HV interval. This case is to our knowledge the first cas of alternating bundle branch block in which his bundle activity was recorded in man. In case 2, the patient had atrial fibrilation and His bundle recordings were performed while differents degrees of left bundle branch block were present: The mechanism of the alternation and the concept of "masquerading" block are discussed. It is suggested that this type of block represents a right bundle branch block associated with severe lesions of the "left system".

  9. Clinical presentation and opportunistic infections in HIV-1, HIV-2 and HIV-1/2 dual seropositive patients in Guinea-Bissau

    DEFF Research Database (Denmark)

    Sørensen, Allan; Jespersen, Sanne; Katzenstein, Terese L

    2016-01-01

    HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Methods: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Sim~ao Mendes in Guinea......-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Results: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive...... antigen. Conclusion: HIV-1 and HIV-1/2 seropositive patients have lower CD4 cell counts than HIV-2 seropositive patients when diagnosed with HIV with only minor clinical and demographic differences among groups. Few patients were diagnosed with TB and cryptococcal disease was not found to be a major...

  10. Women and HIV

    Science.gov (United States)

    ... Consumer Information by Audience For Women Women and HIV: Get the Facts on HIV Testing, Prevention, and Treatment Share Tweet Linkedin Pin ... How can you lower your chance of HIV? HIV Quick Facts What is HIV? HIV is the ...

  11. Correlation of Naturally Occurring HIV-1 Resistance to DEB025 with Capsid Amino Acid Polymorphisms

    Directory of Open Access Journals (Sweden)

    Brigitte Rosenwirth

    2013-03-01

    Full Text Available DEB025 (alisporivir is a synthetic cyclosporine with inhibitory activity against human immunodeficiency virus type-1 (HIV-1 and hepatitis C virus (HCV. It binds to cyclophilin A (CypA and blocks essential functions of CypA in the viral replication cycles of both viruses. DEB025 inhibits clinical HIV-1 isolates in vitro and decreases HIV-1 virus load in the majority of patients. HIV-1 isolates being naturally resistant to DEB025 have been detected in vitro and in nonresponder patients. By sequence analysis of their capsid protein (CA region, two amino acid polymorphisms that correlated with DEB025 resistance were identified: H87Q and I91N, both located in the CypA-binding loop of the CA protein of HIV-1. The H87Q change was by far more abundant than I91N. Additional polymorphisms in the CypA-binding loop (positions 86, 91 and 96, as well as in the N-terminal loop of CA were detected in resistant isolates and are assumed to contribute to the degree of resistance. These amino acid changes may modulate the conformation of the CypA-binding loop of CA in such a way that binding and/or isomerase function of CypA are no longer necessary for virus replication. The resistant HIV-1 isolates thus are CypA-independent.

  12. Controlling cellular P-TEFb activity by the HIV-1 transcriptional transactivator Tat.

    Directory of Open Access Journals (Sweden)

    Lisa Muniz

    Full Text Available The human immunodeficiency virus 1 (HIV-1 transcriptional transactivator (Tat is essential for synthesis of full-length transcripts from the integrated viral genome by RNA polymerase II (Pol II. Tat recruits the host positive transcription elongation factor b (P-TEFb to the HIV-1 promoter through binding to the transactivator RNA (TAR at the 5'-end of the nascent HIV transcript. P-TEFb is a general Pol II transcription factor; its cellular activity is controlled by the 7SK small nuclear RNA (snRNA and the HEXIM1 protein, which sequester P-TEFb into transcriptionally inactive 7SK/HEXIM/P-TEFb snRNP. Besides targeting P-TEFb to HIV transcription, Tat also increases the nuclear level of active P-TEFb through promoting its dissociation from the 7SK/HEXIM/P-TEFb RNP by an unclear mechanism. In this study, by using in vitro and in vivo RNA-protein binding assays, we demonstrate that HIV-1 Tat binds with high specificity and efficiency to an evolutionarily highly conserved stem-bulge-stem motif of the 5'-hairpin of human 7SK snRNA. The newly discovered Tat-binding motif of 7SK is structurally and functionally indistinguishable from the extensively characterized Tat-binding site of HIV TAR and importantly, it is imbedded in the HEXIM-binding elements of 7SK snRNA. We show that Tat efficiently replaces HEXIM1 on the 7SK snRNA in vivo and therefore, it promotes the disassembly of the 7SK/HEXIM/P-TEFb negative transcriptional regulatory snRNP to augment the nuclear level of active P-TEFb. This is the first demonstration that HIV-1 specifically targets an important cellular regulatory RNA, most probably to promote viral transcription and replication. Demonstration that the human 7SK snRNA carries a TAR RNA-like Tat-binding element that is essential for the normal transcriptional regulatory function of 7SK questions the viability of HIV therapeutic approaches based on small drugs blocking the Tat-binding site of HIV TAR.

  13. E-Block: A Tangible Programming Tool with Graphical Blocks

    Directory of Open Access Journals (Sweden)

    Danli Wang

    2013-01-01

    Full Text Available This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transferred to computer by microcomputers and then translated into semantic information. The system applies wireless and infrared technologies and provides user with feedbacks on both screen and programming blocks. Preliminary user studies using observation and user interview methods are shown for E-Block's prototype. The test results prove that E-Block is attractive to children and easy to learn and use. The project also highlights potential advantages of using single chip microcomputer (SCM technology to develop tangible programming tools for children.

  14. Systematic Protein-Protein Docking and Molecular Dynamics Studies of HIV-1 gp120 and CD4: Insights for New Drug Development

    Directory of Open Access Journals (Sweden)

    M. Rizman-Idid

    2011-12-01

    Full Text Available Background and the purpose of the study: The interactions between HIV-1 gp120 and mutated CD4 proteins were investigated in order to identify a lead structure for therapy based on competitive blocking of the HIV binding receptor for human T-cells. Crystal structures of HIV gp120-CD4 complexes reveal a close interaction of the virus receptor with CD4 Phe43, which is embedded in a pocket of the virus protein.Methods: This study applies computer simulations to determine the best binding of amino acid 43 CD4 mutants to HIV gp120. Besides natural CD4, three mutants carrying alternate aromatic residues His, Trp and Tyr at position 43 were investigated. Several docking programs were applied on isolated proteins based on selected crystal structures of gp120-CD4 complexes, as well as a 5 ns molecular dynamics study on the protein complexes. The initial structures were minimized in Gromacs to avoid crystal packing effects, and then subjected to docking experiments using AutoDock4, FireDock, ClusPro and ZDock. In molecular dynamics, the Gibbs free binding energy was calculated for the gp120-CD4 complexes. The docking outputs were analyzed on energy within the respective docking software.Results and conclusion: Visualization and hydrogen bonding analysis were performed using the Swiss-PdbViewer. Strong binding to HIV gp120 can be achieved with an extended aromatic group (Trp. However, the sterical demand of the interaction affects the binding kinetics. In conclusion, a ligand for an efficient blocking of HIV gp120 should involve an extended but conformational flexible aromatic group, i.e. a biphenyl. A docking study on biphenylalanine-43 confirms this expectation

  15. Comparative brain pathology of HIV-seronegative and HIV-infected drug addicts.

    Science.gov (United States)

    Makrigeorgi-Butera, M; Hagel, C; Laas, R; Puschel, K; Stavrou, D

    1996-01-01

    Early stages of infection with human immunodeficiency virus (HIV) were studied in HIV-seropositive drug addicts. Since heroin users are immunocompromized even in the absence of HIV infection, the aim of the present study was to compare the morphological alterations present in HIV-seronegative and HIV-seropositive drug addicts. A total of 60 cases (32 HIV-seronegative subjects, 21 HIV-seropositive patients without signs of acquired immunodeficiency syndrome (AIDS), and 7 HIV-seropositive patients with signs of AIDS) were investigated macroscopically, histologically, and immunohistochemically HIV-seronegative patients presented more frequently with acute drug intoxication, died at a significantly younger age than HIV-seropositive patients, and were found to suffer more frequently from alcohol-related changes. These results indicated that HIV-seronegative and HIV-seropositive patients differed possibly in their drug consumption and also in their general conditions of life. In accordance with previous reports activated microglia and a diffuse astrogliosis in the white matter were detected at a significantly higher frequency and found to be more severe in HIV-seropositive subjects than in HIV-seronegative addicts. A lymphocytic meningitis was present in 6 of 21 HIV-seropositive patients but in none of the HIV-seronegative patients. Perivascular infiltrates consisting of lymphocytes and macrophages were detected at similar frequencies in HIV-seronegative and HIV-seropositive patients but were significantly more severe in patients suffering from lymphocytic meningitis or purulent encephalitis. Opportunistic infections were only demonstrated in 2 AIDS cases. In 10 of the HIV-seronegative patients and in 3 of the HIV-seropositive patients CD68-and Ham56-positive multinucleated cells were detected scattered in the subarachnoidal space exclusively over the frontal cortex.

  16. Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

    Science.gov (United States)

    Bomsel, Morgane; Ganor, Yonatan

    2017-12-01

    The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

  17. E-Block: A Tangible Programming Tool with Graphical Blocks

    OpenAIRE

    Danli Wang; Yang Zhang; Shengyong Chen

    2013-01-01

    This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transfer...

  18. Maraviroc is associated with latent HIV-1 reactivation through NF-κB activation in resting CD4+ T cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

    Science.gov (United States)

    Madrid-Elena, Nadia; García-Bermejo, María Laura; Serrano-Villar, Sergio; Díaz-de Santiago, Alberto; Sastre, Beatriz; Gutiérrez, Carolina; Dronda, Fernando; Coronel Díaz, María; Domínguez, Ester; López-Huertas, María Rosa; Hernández-Novoa, Beatriz; Moreno, Santiago

    2018-02-14

    Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and others have suggested that maraviroc could reactivate latent HIV-1. To test the latency reversing potential of maraviroc and the mechanisms involved, we performed a phase-II, single-center, open-label study in which maraviroc was administered for 10 days to 20 HIV-1-infected individuals on suppressive antiretroviral therapy (Eudra CT: 2012-003215-66). All patients completed full maraviroc dosing and follow up. The primary endpoint was to study whether maraviroc may reactivate HIV-1 latency, eliciting signalling pathways involved in the viral reactivation. An increase in HIV-1 transcription in resting CD4 + T-cells, estimated by HIV-1 unspliced RNA, was observed. Moreover, activation of the NF-κB transcription factor was observed in these cells. In contrast, AP-1 and NFAT activity was not detected. To elucidate the mechanism of NF-κB activation by maraviroc, we have evaluated in HeLa P4 C5 cells, which stably express CCR5, if maraviroc could be acting as a partial CCR5-agonist, with no other mechanisms or pathways involved. Our results show that maraviroc can induce NF-κB activity and NF-κB target genes expression by CCR5 binding, since the use of TAK779, a CCR5 inhibitor, blocked NF-κB activation and functionality. Taken together, we show that maraviroc may have a role in the activation of latent virus transcription through the activation of NF-κB as a result of binding CCR5. Our results strongly support a novel use of maraviroc as a potential latency reversal agent in HIV-1-infected patients. IMPORTANCE HIV-1 persistence in a small pool of long-lived latently infected resting CD4 + T-cells is a major barrier to viral eradication in HIV-1-infected patients on antiretroviral therapy. A potential strategy to cure HIV-1-infection is the use of latency reversing agents to eliminate the reservoirs established in resting CD4 + T-cells. As no drug has been shown to be completely

  19. Living with HIV

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Syndicated Content Website Feedback HIV/AIDS Living With HIV Language: English (US) Español (Spanish) Recommend on Facebook ...

  20. Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection.

    Directory of Open Access Journals (Sweden)

    Yun Shan Goh

    2016-04-01

    Full Text Available Nontyphoidal strains of Salmonella are a leading cause of death among HIV-infected Africans. Antibody-induced complement-mediated killing protects healthy Africans against Salmonella, but increased levels of anti-lipopolysaccharide (LPS antibodies in some HIV-infected African adults block this killing. The objective was to understand how these high levels of anti-LPS antibodies interfere with the killing of Salmonella.Sera and affinity-purified antibodies from African HIV-infected adults that failed to kill invasive S. Typhimurium D23580 were compared to sera from HIV-uninfected and HIV-infected subjects with bactericidal activity. The failure of sera from certain HIV-infected subjects to kill Salmonella was found to be due to an inherent inhibitory effect of anti-LPS antibodies. This inhibition was concentration-dependent and strongly associated with IgA and IgG2 anti-LPS antibodies (p<0.0001 for both. IgG anti-LPS antibodies, from sera of HIV-infected individuals that inhibit killing at high concentration, induced killing when diluted. Conversely, IgG, from sera of HIV-uninfected adults that induce killing, inhibited killing when concentrated. IgM anti-LPS antibodies from all subjects also induced Salmonella killing. Finally, the inhibitory effect of high concentrations of anti-LPS antibodies is seen with IgM as well as IgG and IgA. No correlation was found between affinity or avidity, or complement deposition or consumption, and inhibition of killing.IgG and IgM classes of anti-S. Typhimurium LPS antibodies from HIV-infected and HIV-uninfected individuals are bactericidal, while at very high concentrations, anti-LPS antibodies of all classes inhibit in vitro killing of Salmonella. This could be due to a variety of mechanisms relating to the poor ability of IgA and IgG2 to activate complement, and deposition of complement at sites where it cannot insert in the bacterial membrane. Vaccine trials are required to understand the significance of

  1. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Directory of Open Access Journals (Sweden)

    Alexander Zhyvoloup

    2017-07-01

    Full Text Available HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  2. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    Science.gov (United States)

    Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

    2017-07-01

    HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  3. Depression in perinatally HIV-infected pregnant women compared to non-perinatally HIV-infected and HIV-uninfected pregnant women.

    Science.gov (United States)

    Angrand, Ruth C; Sperling, Rhoda; Roccobono, Kinga; Osborne, Lauren M; Jao, Jennifer

    2018-05-18

    "Depression (as noted in chart by a physician)" was compared between HIV infected pregnant women and controls. Perinatally HIV-infected (PHIV), non-perinatally HIV-infected (NPHIV), and HIV-uninfected (HIV-U) pregnant women were all compared using a logistic regression model. Overall, HIV-infected women had higher rates of depression than HIV-U, with PHIV women demonstrating a clinically and statistically significant increased risk compared to HIV-U women [adjusted OR: 15.9, 95% CI = 1.8-143.8]. Future studies in larger populations are warranted to confirm these findings and further elucidate mental health outcomes of PHIV and NPHIV pregnant women.

  4. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2010-01-01

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  5. HIV antibodies for treatment of HIV infection.

    Science.gov (United States)

    Margolis, David M; Koup, Richard A; Ferrari, Guido

    2017-01-01

    The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  6. A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay.

    Science.gov (United States)

    Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Mancon, Alessandro; Marcos, Mª Angeles; Mileto, Davide; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

    2017-07-01

    Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System. ¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS ® AmpliPrep/COBAS ® TaqMan ® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log 10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be <0.3 log 10 cp/mL for VERIS HIV-1 Assay versus COBAS HIV-1 Test and RealTime HIV-1 Assay, and <0.5 log 10 cp/mL versus VERSANT HIV-1 Assay. Analysis on 174 specimens tested with the 0.175mL volume VERIS HIV-1 Assay and COBAS HIV-1 Test showed average bias of 0.39 log 10 cp/mL. Patient monitoring results using VERIS HIV-1 Assay demonstrated similar viral load trends over time to all comparators. The VERIS HIV-1 Assay for use on the DxN VERIS System demonstrated comparable clinical performance to COBAS ® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

    International Nuclear Information System (INIS)

    Qi, Zhi; Pan, Chungen; Lu, Hong; Shui, Yuan; Li, Lin; Li, Xiaojuan; Xu, Xueqing; Liu, Shuwen; Jiang, Shibo

    2010-01-01

    Research highlights: → One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. → N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. → These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.

  8. Molecular HIV screening.

    Science.gov (United States)

    Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

    2013-09-01

    Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

  9. Experiences of HIV stigma: the role of visible symptoms, HIV centrality and community attachment for people living with HIV.

    Science.gov (United States)

    Brener, Loren; Callander, Denton; Slavin, Sean; de Wit, John

    2013-01-01

    For many people living with HIV (PLHIV), disclosure or concealment of their HIV status may be under their personal control; however, for PLHIV with visible symptoms of their illness, disclosure may no longer be a choice. Previous research suggests that those with visible HIV symptoms have poorer mental and physical health than those without visible HIV symptoms. This study aimed to extend these findings and assess the role of perceived centrality of HIV in the lives of PLHIV as well as the role of attachment to an HIV-positive community in understanding the negative effects on health and well-being for PLHIV with visible HIV symptoms. Participants were 697 PLHIV who completed an online survey that assessed symptom visibility, HIV-status disclosure, perceived stigma, health and well-being, how central HIV was to identity and HIV community attachment. Results indicate that those with visible symptoms experienced more HIV-related stigma and had poorer outcomes on a range of psychological and mental health measures than those who were able to conceal their stigma. These effects remained after controlling for length of time since diagnosis, time on HIV treatment, perceived health satisfaction and age. PLHIV with visible symptoms also reported that HIV was more central to their identity and reported greater attachment to an HIV-positive community. Furthermore, findings suggest that while HIV centrality appears to increase the negative effects of having visible symptoms associated with HIV, greater community attachment seems to ameliorate these effects. This suggests the need for a nuanced understanding of the implications of visible HIV symptoms for PLHIV. The study also highlights the potential benefits of HIV-positive community attachment in buffering PLHIV from the negative effect of visible HIV symptoms on their health and well-being.

  10. Predictors of HIV, HIV Risk Perception, and HIV Worry Among Adolescent Girls and Young Women in Lilongwe, Malawi.

    Science.gov (United States)

    Price, Joan T; Rosenberg, Nora E; Vansia, Dhrutika; Phanga, Twambilile; Bhushan, Nivedita L; Maseko, Bertha; Brar, Savvy K; Hosseinipour, Mina C; Tang, Jennifer H; Bekker, Linda-Gail; Pettifor, Audrey

    2018-01-01

    Adolescent girls and young women (AGYW) in sub-Saharan Africa have high HIV prevalence and incidence. We sought to understand which HIV risk factors individually and in combination contribute to risk, and whether these factors are associated with HIV worry and risk perception. This study is ongoing at 4 public health centers in Lilongwe, Malawi (2016-2017). AGYW of 15-24 years old were recruited to participate in a study assessing 4 models of service delivery. At each health center, participants completed a baseline survey assessing socioeconomic, behavioral, biomedical, and partnership characteristics; self-reported HIV status; and, if HIV-uninfected, HIV risk perception (high versus low or none) and HIV worry (any versus none). We analyzed associations between baseline characteristics and HIV prevalence, risk perception, and worry. Among 1000 AGYW, median age was 19 years (IQR: 17-21). Thirty-three participants reported being HIV-infected. Fifteen characteristics were associated with HIV infection. Having more risk factors was associated with higher HIV prevalence (≤4 factors, 0.5%; 5-8 factors, 6%; >8 factors, 21%). Having more risk factors was also associated with higher risk perception (P risk factors, 52% did not consider themselves to be at high risk and 21% did not report any HIV worry. Most AGYW perceive little risk of HIV acquisition, even those at highest risk. As a critical gap in the HIV prevention cascade, accurate risk perception is needed to tailor effective and sustained combination prevention strategies for this vulnerable population.

  11. Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population.

    Science.gov (United States)

    Peters, Philip J; Westheimer, Emily; Cohen, Stephanie; Hightow-Weidman, Lisa B; Moss, Nicholas; Tsoi, Benjamin; Hall, Laura; Fann, Charles; Daskalakis, Demetre C; Beagle, Steve; Patel, Pragna; Radix, Asa; Foust, Evelyn; Kohn, Robert P; Marmorino, Jenni; Pandori, Mark; Fu, Jie; Samandari, Taraz; Gay, Cynthia L

    2016-02-16

    Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. Number and proportion with acute HIV infections detected. Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both

  12. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

    Directory of Open Access Journals (Sweden)

    Sandhya Boyapalle

    Full Text Available Human immunodeficiency virus (HIV types 1 and 2 (HIV-1 and HIV-2 are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162 viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

  13. Focus on the therapeutic efficacy of 3BNC117 against HIV-1: In vitro studies, in vivo studies, clinical trials and challenges.

    Science.gov (United States)

    Liu, Zhi-Jun; Bai, Jing; Liu, Feng-Li; Zhang, Xiang-Yang; Wang, Jing-Zhang

    2017-11-01

    3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo. The outcomes of Phase I and Phase IIa clinical trials in 2015 and 2016 showed the safety, tolerability, and therapeutic efficacy of 3BNC117 in HIV-1-infected human individuals. Nevertheless, anti-3BNC117 antibodies and HIV-1 strains resistant to 3BNC117 pose clinical challenges to immunotherapy with 3BNC117, so potential strategies for optimizing the potency of 3BNC117 are suggested here. Predictably, HIV-1 prevention and AIDS treatment will benefit from combinational immunotherapies with 3BNC117 and other pharmaceuticals (bNAbs, antiretroviral medicines, viral inducers, etc.) in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Shifting the Paradigm: Using HIV Surveillance Data as a Foundation for Improving HIV Care and Preventing HIV Infection

    Science.gov (United States)

    Sweeney, Patricia; Gardner, Lytt I; Buchacz, Kate; Garland, Pamela Morse; Mugavero, Michael J; Bosshart, Jeffrey T; Shouse, R Luke; Bertolli, Jeanne

    2013-01-01

    Context Reducing HIV incidence in the United States and improving health outcomes for people living with HIV hinge on improving access to highly effective treatment and overcoming barriers to continuous treatment. Using laboratory tests routinely reported for HIV surveillance to monitor individuals’ receipt of HIV care and contacting them to facilitate optimal care could help achieve these objectives. Historically, surveillance-based public health intervention with individuals for HIV control has been controversial because of concerns that risks to privacy and autonomy could outweigh benefits. But with the availability of lifesaving, transmission-interrupting treatment for HIV infection, some health departments have begun surveillance-based outreach to facilitate HIV medical care. Methods Guided by ethics frameworks, we explored the ethical arguments for changing the uses of HIV surveillance data. To identify ethical, procedural, and strategic considerations, we reviewed the activities of health departments that are using HIV surveillance data to contact persons identified as needing assistance with initiating or returning to care. Findings Although privacy concerns surrounding the uses of HIV surveillance data still exist, there are ethical concerns associated with not using HIV surveillance to maximize the benefits from HIV medical care and treatment. Early efforts to use surveillance data to facilitate optimal HIV medical care illustrate how the ethical burdens may vary depending on the local context and the specifics of implementation. Health departments laid the foundation for these activities by engaging stakeholders to gain their trust in sharing sensitive information; establishing or strengthening legal, policy and governance infrastructure; and developing communication and follow-up protocols that protect privacy. Conclusions We describe a shift toward using HIV surveillance to facilitate optimal HIV care. Health departments should review the

  15. Architecture and Assembly of HIV Integrase Multimers in the Absence of DNA Substrates*

    Science.gov (United States)

    Bojja, Ravi Shankar; Andrake, Mark D.; Merkel, George; Weigand, Steven; Dunbrack, Roland L.; Skalka, Anna Marie

    2013-01-01

    We have applied small angle x-ray scattering and protein cross-linking coupled with mass spectrometry to determine the architectures of full-length HIV integrase (IN) dimers in solution. By blocking interactions that stabilize either a core-core domain interface or N-terminal domain intermolecular contacts, we show that full-length HIV IN can form two dimer types. One is an expected dimer, characterized by interactions between two catalytic core domains. The other dimer is stabilized by interactions of the N-terminal domain of one monomer with the C-terminal domain and catalytic core domain of the second monomer as well as direct interactions between the two C-terminal domains. This organization is similar to the “reaching dimer” previously described for wild type ASV apoIN and resembles the inner, substrate binding dimer in the crystal structure of the PFV intasome. Results from our small angle x-ray scattering and modeling studies indicate that in the absence of its DNA substrate, the HIV IN tetramer assembles as two stacked reaching dimers that are stabilized by core-core interactions. These models of full-length HIV IN provide new insight into multimer assembly and suggest additional approaches for enzyme inhibition. PMID:23322775

  16. Serum neutralizing activities from a Beijing homosexual male cohort infected with different subtypes of HIV-1 in China.

    Directory of Open Access Journals (Sweden)

    Mingshun Zhang

    Full Text Available Protective antibodies play a critical role in an effective HIV vaccine; however, eliciting antibodies to block infection by viruses from diverse genetic subtypes remains a major challenge. As the world's most populous country, China has been under the threat of at least three major subtypes of circulating HIV-1 viruses. Understanding the cross reactivity and specificities of serum antibody responses that mediate broad neutralization of the virus in HIV-1 infected Chinese patients will provide valuable information for the design of vaccines to prevent HIV-1 transmission in China. Sera from a cohort of homosexual men, who have been managed by a major HIV clinical center in Beijing, China, were analyzed for cross-sectional neutralizing activities against pseudotyped viruses expressing Env antigens of the major subtype viruses (AE, BC and B subtypes circulating in China. Neutralizing activities in infected patients' blood were most capable of neutralizing viruses in the homologous subtype; however, a subset of blood samples was able to achieve broad neutralizing activities across different subtypes. Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples. Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population. Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

  17. [HIV Stigma and Spiritual Care in People Living With HIV].

    Science.gov (United States)

    Yu, Chia-Hui; Chiu, Yi-Chi; Cheng, Su-Fen; Ko, Nai-Ying

    2018-06-01

    HIV infection has been a manageable and chronic illness in Taiwan since the highly active antiretroviral therapy was introduced in 1997. HIV infection is a stigmatized disease due to its perceived association with risky behaviors. HIV often carries a negative image, and people living with HIV(PLWH) face discrimination on multiple fronts. Internalized HIV stigma impacts the spiritual health of people living with HIV in terms of increased levels of shame, self-blame, fear of disclosing HIV status, and isolation and decreased value and connections with God, others, the environment, and the self. Nursing professionals provide holistic care for all people living with HIV and value their lives in order to achieve the harmony of body, mind, and spirit. This article describes the stigma that is currently associated with HIV and how stigma-related discrimination affects the spiritual health of PLWH and then proposes how to reduce discrimination and stigma in order to improve the spiritual health of PLWH through appropriate spiritual care. Reducing HIV stigma and promoting spiritual well-being will enable Taiwan to achieve the 'Three Zeros' of zero discrimination, zero infection, and zero death advocated by the Joint United Nations Programme on HIV/AIDS for ending the AIDS epidemic in 2030.

  18. Poly(ferrocenylsilane)-block-Polylactide Block Copolymers

    NARCIS (Netherlands)

    Roerdink, M.; van Zanten, Thomas S.; Hempenius, Mark A.; Zhong, Zhiyuan; Feijen, Jan; Vancso, Gyula J.

    2007-01-01

    A PFS/PLA block copolymer was studied to probe the effect of strong surface interactions on pattern formation in PFS block copolymer thin films. Successful synthesis of PFS-b-PLA was demonstrated. Thin films of these polymers show phase separation to form PFS microdomains in a PLA matrix, and

  19. A systematic review of measures of HIV/AIDS stigma in paediatric HIV-infected and HIV-affected populations

    Science.gov (United States)

    McAteer, Carole Ian; Truong, Nhan-Ai Thi; Aluoch, Josephine; Deathe, Andrew Roland; Nyandiko, Winstone M; Marete, Irene; Vreeman, Rachel Christine

    2016-01-01

    Introduction HIV-related stigma impacts the quality of life and care management of HIV-infected and HIV-affected individuals, but how we measure stigma and its impact on children and adolescents has less often been described. Methods We conducted a systematic review of studies that measured HIV-related stigma with a quantitative tool in paediatric HIV-infected and HIV-affected populations. Results and discussion Varying measures have been used to assess stigma in paediatric populations, with most studies utilizing the full or variant form of the HIV Stigma Scale that has been validated in adult populations and utilized with paediatric populations in Africa, Asia and the United States. Other common measures included the Perceived Public Stigma Against Children Affected by HIV, primarily utilized and validated in China. Few studies implored item validation techniques with the population of interest, although scales were used in a different cultural context from the origin of the scale. Conclusions Many stigma measures have been used to assess HIV stigma in paediatric populations, globally, but few have implored methods for cultural adaptation and content validity. PMID:27717409

  20. Novel 3′-Processing Integrase Activity Assay by Real-Time PCR for Screening and Identification of HIV-1 Integrase Inhibitors

    Directory of Open Access Journals (Sweden)

    Supachai Sakkhachornphop

    2015-01-01

    Full Text Available The 3′-end processing (3′P of each viral long terminal repeat (LTR during human immunodeficiency virus type-1 (HIV-1 integration is a vital step in the HIV life cycle. Blocking the 3′P using 3′P inhibitor has recently become an attractive strategy for HIV-1 therapeutic intervention. Recently, we have developed a novel real-time PCR based assay for the detection of 3′P activity in vitro. The methodology usually involves biotinylated HIV-1 LTR, HIV-1 integrase (IN, and specific primers and probe. In this novel assay, we designed the HIV-1 LTR substrate based on a sequence with a homology to HIV-1 LTR labeled at its 3′ end with biotin on the sense strand. Two nucleotides at the 3′ end were subsequently removed by IN activity. Only two nucleotides labeled biotin were captured on an avidin-coated tube; therefore, inhibiting the binding of primers and probe results in late signals in the real-time PCR. This novel assay has successfully detected both the 3′P activity of HIV-1 IN and the anti-IN activity by Raltegravir and sodium azide agent. This real-time PCR assay has been shown to be effective and inexpensive for a high-throughput screening of novel IN inhibitors.

  1. EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

    Science.gov (United States)

    Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam

    2015-09-01

    Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.

  2. Adherence to feeding guidelines among HIV-infected and HIV ...

    African Journals Online (AJOL)

    For infants older than six months, complementary feeding was more common among HIV-uninfected (100%) than HIV-infected mothers (41.7%; P<0.001). Among infants of all ages, none of the HIV-uninfected and 45% of HIV-infected mothers were replacement feeding (p<0.001). More than a half (59.8%) of the mothers ...

  3. Host and viral determinants for MxB restriction of HIV-1 infection.

    Science.gov (United States)

    Matreyek, Kenneth A; Wang, Weifeng; Serrao, Erik; Singh, Parmit Kumar; Levin, Henry L; Engelman, Alan

    2014-10-25

    Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite considerable evidence demonstrating the breadth of antiviral activity of MxA, human MxB was only recently discovered to specifically inhibit lentiviruses. Here we assess both host and viral determinants that underlie MxB restriction of HIV-1 infection. Heterologous expression of MxB in human osteosarcoma cells potently inhibited HIV-1 infection (~12-fold), yet had little to no effect on divergent retroviruses. The anti-HIV effect manifested as a partial block in the formation of 2-long terminal repeat circle DNA and hence nuclear import, and we accordingly found evidence for an additional post-nuclear entry block. A large number of previously characterized capsid mutations, as well as mutations that abrogated integrase activity, counteracted MxB restriction. MxB expression suppressed integration into gene-enriched regions of chromosomes, similar to affects observed previously when cells were depleted for nuclear transport factors such as transportin 3. MxB activity did not require predicted GTPase active site residues or a series of unstructured loops within the stalk domain that confer functional oligomerization to related dynamin family proteins. In contrast, we observed an N-terminal stretch of residues in MxB to harbor key determinants. Protein localization conferred by a nuclear localization signal (NLS) within the N-terminal 25 residues, which was critical, was fully rescuable by a heterologous NLS. Consistent with this observation, a heterologous nuclear export sequence (NES) abolished full-length MxB activity. We additionally mapped sub-regions within amino acids 26-90 that contribute to MxB activity, finding sequences present within residues 27-50 particularly important. MxB inhibits HIV-1 by interfering with minimally two steps of infection

  4. HIV Status Discordance: Associated Factors Among HIV Positive ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    infection for a partner of a person with HIV is about 10%, with higher annual transmission rates ... We recommend the tracking of both men and women as index cases in other to reduce HIV .... HIV status was accepted as known only if backed.

  5. Marcadores virológicos no convencionales en pacientes infectados con el virus de la inmunodeficiencia humana: ADN HIV-T, ADN HIV- 2LTR y ARN de HIV Non conventional virological markers in HIV-infected patients: T-HIV DNA, 2LTR-HIV DNA and HIV RNA

    Directory of Open Access Journals (Sweden)

    Rosana Gariglio

    2004-10-01

    Full Text Available La terapia antirretroviral de alta eficacia (TAAE induce una reducción marcada y persistente de la viremia plasmática, contribuyendo a disminuir la mortalidad y morbilidad de los pacientes HIV-positivos. Así, la carga viral (CV es el método de referencia para evaluar la eficacia terapéutica. Sin embargo, aun en presencia de una TAAE eficiente no se ha logrado la erradicación viral. En este estudio analizamos la presencia del ADN total de HIV (ADN HIV-T, del ADN no integrado con 2LTR (ADN HIV-2LTR y del ARN de HIV, en un grupo de 55 pacientes HIV-positivos en distintos estadios clínicos, con y sin TAAE, mediante ensayos de PCR con revelado colorimétrico en microplaca, optimizados en nuestro laboratorio. La sensibilidad clínica del ARN del HIV fue evaluada con el bDNA, resultando del 74% y del 64%, respectivamente, con una concordancia del 85%. Este ensayo podría ser utilizado en el seguimiento de pacientes bajo TAAE. El ADN HIV-2LTR resultó positivo en el 54% aunque estuvo ausente en pacientes con elevada CV. Este marcador se consideraba un producto lábil y su presencia se asociaba a infección reciente. Sin embargo, actuales evidencias ponen en discusión su estabilidad por lo que su significado clínico debe ser reconsiderado. La ausencia del ADN HIV-2LTR en pacientes con CV detectable puede relacionarse con la heterogeneidad de la secuencia utilizada para su detección. El ADN HIV-T estuvo presente en el 100% de las muestras y resultaría relevante como marcador de remisión cuando se dispongan de terapias que efectivamente erradiquen la infección.Highly active antiretroviral therapy (HAART induces a persistent reduction of the plasmatic viremia, contributing to decrease mortality and morbidity of infected people with human immunodeficiency virus (HIV. Thus, viral load (VL is the reference method to evaluate therapy effectiveness. However, even in the presence of efficient HAART viral eradication was yet not achieved. In this

  6. Radiological differences between HIV-positive and HIV-negative children with cholesteatoma.

    Science.gov (United States)

    McGuire, J K; Fagan, J J; Wojno, M; Manning, K; Harris, T

    2018-07-01

    HIV-positive children are possibly more prone to developing cholesteatoma. Chronic inflammation of the middle ear cleft may be more common in patients with HIV and this may predispose HIV-positive children to developing cholesteatoma. There are no studies that describe the radiological morphology of the middle ear cleft in HIV-positive compared to HIV-negative children with cholesteatoma. Compare the radiological differences of the middle ear cleft in HIV-positive and HIV-negative children with cholesteatoma. A retrospective, cross-sectional, observational analytical review of patients with cholesteatoma at our institute over a 6 year period. Forty patients were included in the study, 11 of whom had bilateral cholesteatoma and therefore 51 ears were eligible for our evaluation. HIV-positive patients had smaller (p=0.02) mastoid air cell systems (MACS). Forty percent of HIV-positive patients had sclerotic mastoids, whereas the rate was 3% in HIV-negative ears (p<0.02). Eighty-two percent of the HIV-positive patients had bilateral cholesteatoma compared to 7% of the control group (p<0.02). There was no difference between the 2 groups with regards to opacification of the middle ear cleft, bony erosion of middle ear structures, Eustachian tube obstruction or soft tissue occlusion of the post-nasal space. HIV-positive paediatric patients with cholesteatoma are more likely to have smaller, sclerotic mastoids compared to HIV-negative patients. They are significantly more likely to have bilateral cholesteatoma. This may have implications in terms of surveillance of HIV-positive children, as well as, an approach to management, recurrence and follow-up. HIV infection should be flagged as a risk factor for developing cholesteatoma. Copyright © 2018. Published by Elsevier B.V.

  7. Basic HIV/AIDS Statistics

    Science.gov (United States)

    ... HIV Syndicated Content Website Feedback HIV/AIDS Basic Statistics Recommend on Facebook Tweet Share Compartir HIV and ... HIV. Interested in learning more about CDC's HIV statistics? Terms, Definitions, and Calculations Used in CDC HIV ...

  8. Correlates of HIV infection among people visiting public HIV ...

    African Journals Online (AJOL)

    Correlates of HIV infection among people visiting public HIV counseling and testing clinics in Mpumalanga, ... Background: HIV voluntary counselling and testing (VCT) reduces high-risk sexual behaviour. ... AJOL African Journals Online.

  9. Synthesis and evaluation of "AZT-HEPT", "AZT-pyridinone", and "ddC-HEPT" conjugates as inhibitors of HIV reverse transcriptase.

    Science.gov (United States)

    Pontikis, R; Dollé, V; Guillaumel, J; Dechaux, E; Note, R; Nguyen, C H; Legraverend, M; Bisagni, E; Aubertin, A M; Grierson, D S; Monneret, C

    2000-05-18

    To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component (AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 microM anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC(50) = 0.45 microM) against HIV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.

  10. Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.

    Directory of Open Access Journals (Sweden)

    Lijun Chao

    Full Text Available The HIV-1 envelope glycoprotein (Env gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no, immunogenicity to humans. Here, we found that the C-terminal fragment (aa 462-521 of the human POB1 (the partner of RalBP1, designated C60, is an HIV-1 fusion inhibitor. It bound to N36, the peptide derived from the N-terminal heptad repeat (NHR of gp41, and to the six-helix bundle (6-HB formed by N36 and C34, a CHR-peptide, but it did not bind to C34. Unlike the CHR-peptides, C60 did not block gp41 6-HB formation. Rather, results suggest that C60 inhibits HIV-1 fusion by binding to the 6-HB, in particular, the residues in the gp41 NHR domain that are exposed on the surface of 6-HB. Since 6-HB plays a crucial role in the late stage of fusion between the viral envelope and endosomal membrane during the endocytic process of HIV-1, C60 may serve as a host restriction factor to suppress HIV-1 entry into CD4+ T lymphocytes. Taken together, it can be concluded from these results that C60 can be used as a lead for the development of anti-HIV-1 therapeutics or microbicides for the treatment and prevention of HIV-1 infection, as well as a molecular probe to study the fusogenic mechanism of HIV-1.

  11. Block and sub-block boundary strengthening in lath martensite

    NARCIS (Netherlands)

    Du, C.; Hoefnagels, J.P.M.; Vaes, R.; Geers, M.G.D.

    2016-01-01

    Well-defined uniaxial micro-tensile tests were performed on lath martensite single block specimens and multi-block specimens with different number of block boundaries parallel to the loading direction. Detailed slip trace analyses consistently revealed that in the {110}<111> slip system with the

  12. On the Eigenvalues and Eigenvectors of Block Triangular Preconditioned Block Matrices

    KAUST Repository

    Pestana, Jennifer

    2014-01-01

    Block lower triangular matrices and block upper triangular matrices are popular preconditioners for 2×2 block matrices. In this note we show that a block lower triangular preconditioner gives the same spectrum as a block upper triangular preconditioner and that the eigenvectors of the two preconditioned matrices are related. © 2014 Society for Industrial and Applied Mathematics.

  13. HIV/AIDS - Multiple Languages

    Science.gov (United States)

    ... HIV - Newly diagnosed with HIV, part 5 - English MP3 Children and HIV - Newly diagnosed with HIV, part 5 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Children and HIV - Newly diagnosed with HIV, part ...

  14. Powder wastes confinement block and manufacturing process of this block

    International Nuclear Information System (INIS)

    Dagot, L.; Brunel, G.

    1996-01-01

    This invention concerns a powder wastes containment block and a manufacturing process of this block. In this block, the waste powder is encapsulated in a thermo hardening polymer as for example an epoxy resin, the encapsulated resin being spread into cement. This block can contain between 45 and 55% in mass of wastes, between 18 and 36% in mass of polymer and between 14 and 32% in mass of cement. Such a containment block can be used for the radioactive wastes storage. (O.M.). 4 refs

  15. HIV/AIDS Coinfection

    Science.gov (United States)

    ... Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  16. HIV and Immunizations

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV and Immunizations Last Reviewed: February 6, 2018 Key ...

  17. HIV Medication Adherence

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Medication Adherence Last Reviewed: January 17, 2018 Key ...

  18. Colorectal mucus binds DC-SIGN and inhibits HIV-1 trans-infection of CD4+ T-lymphocytes.

    Science.gov (United States)

    Stax, Martijn J; Mouser, Emily E I M; van Montfort, Thijs; Sanders, Rogier W; de Vries, Henry J C; Dekker, Henk L; Herrera, Carolina; Speijer, Dave; Pollakis, Georgios; Paxton, William A

    2015-01-01

    Bodily secretions, including breast milk and semen, contain factors that modulate HIV-1 infection. Since anal intercourse caries one of the highest risks for HIV-1 transmission, our aim was to determine whether colorectal mucus (CM) also contains factors interfering with HIV-1 infection and replication. CM from a number of individuals was collected and tested for the capacity to bind DC-SIGN and inhibit HIV-1 cis- or trans-infection of CD4+ T-lymphocytes. To this end, a DC-SIGN binding ELISA, a gp140 trimer competition ELISA and HIV-1 capture/ transfer assays were utilized. Subsequently we aimed to identify the DC-SIGN binding component through biochemical characterization and mass spectrometry analysis. CM was shown to bind DC-SIGN and competes with HIV-1 gp140 trimer for binding. Pre-incubation of Raji-DC-SIGN cells or immature dendritic cells (iDCs) with CM potently inhibits DC-SIGN mediated trans-infection of CD4+ T-lymphocytes with CCR5 and CXCR4 using HIV-1 strains, while no effect on direct infection is observed. Preliminary biochemical characterization demonstrates that the component seems to be large (>100kDa), heat and proteinase K resistant, binds in a α1-3 mannose independent manner and is highly variant between individuals. Immunoprecipitation using DC-SIGN-Fc coated agarose beads followed by mass spectrometry indicated lactoferrin (fragments) and its receptor (intelectin-1) as candidates. Using ELISA we showed that lactoferrin levels within CM correlate with DC-SIGN binding capacity. In conclusion, CM can bind the C-type lectin DC-SIGN and block HIV-1 trans-infection of both CCR5 and CXCR4 using HIV-1 strains. Furthermore, our data indicate that lactoferrin is a DC-SIGN binding component of CM. These results indicate that CM has the potential to interfere with pathogen transmission and modulate immune responses at the colorectal mucosa.

  19. Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

    Directory of Open Access Journals (Sweden)

    Ceña-Diez R

    2016-05-01

    Full Text Available Rafael Ceña-Diez,1–4,* Pilar García-Broncano,1–5,* Francisco Javier de la Mata,4,6 Rafael Gómez,4,6 Mª Ángeles Muñoz-Fernández1–4 1Hospital General Universitario Gregorio Marañon, 2Instituto de Investigación Sanitaria Gregorio Marañon, 3Spanish HIV HGM Biobank, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, 5Laboratory of Viral Infection and Immunity, National Center of Microbiology, Health Institute of Carlos III, Majadahonda, 6Department of Organic Chemistry and Inorganic Chemistry, University of Alcalá, Alcalá de Henares, Madrid, Spain *These authors contributed equally to this work Abstract: The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection. Keywords: G2-S16, dendrimer, HIV-1, SEVI, microbicide, antiretrovirals

  20. Blocked Randomization with Randomly Selected Block Sizes

    Directory of Open Access Journals (Sweden)

    Jimmy Efird

    2010-12-01

    Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  1. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  2. HIV Interventions to Reduce HIV/AIDS Stigma: A Systematic Review

    Science.gov (United States)

    Banks, Bahby; Jonas, Dan; Miles, Margaret Shandor; Smith, Giselle Corbie

    2011-01-01

    We reviewed the literature to determine the effectiveness of HIV-related interventions in reducing HIV/AIDS stigma. Studies selected had randomized controlled trial (RCT), pretest–posttest with a non-randomized control group, or pretest–posttest one group study designs in which HIV-related interventions were being evaluated, and in which HIV/AIDS stigma was one of the outcomes being measured. A checklist was used to extract data from accepted studies, assess their internal validity, and overall quality. Data were extracted from 19 studies, and 14 of these studies demonstrated effectiveness in reducing HIV/ AIDS stigma. Only 2 of these 14 effective studies were considered good studies, based on quality, the extent to which the intervention focused on reducing HIV/AIDS stigma, and the statistics reported to demonstrate effectiveness. Future studies to reduce HIV/AIDS stigma could improve by designing interventions that pay greater attention to internal validity, use validated HIV/AIDS stigma instruments, and achieve both statistical and public health significance. PMID:21088989

  3. HIV-1 replication in cell lines harboring INI1/hSNF5 mutations

    Directory of Open Access Journals (Sweden)

    Wu Xuhong

    2006-08-01

    Full Text Available Abstract Background INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN. It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication. Results We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate. Conclusion Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that

  4. HIV-1 replication in cell lines harboring INI1/hSNF5 mutations.

    Science.gov (United States)

    Sorin, Masha; Yung, Eric; Wu, Xuhong; Kalpana, Ganjam V

    2006-08-31

    INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN). It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication. We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate. Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that presence of INI1 or some other host factor in virions and

  5. Evolution of the health sector response to HIV in Myanmar: progress, challenges and the way forward.

    Science.gov (United States)

    Oo, Htun Nyunt; Hone, San; Fujita, Masami; Maw-Naing, Amaya; Boonto, Krittayawan; Jacobs, Marjolein; Phyu, Sabe; Bollen, Phavady; Cheung, Jacquie; Aung, Htin; Aung Sang, May Thu; Myat Soe, Aye; Pendse, Razia; Murphy, Eamonn

    2016-11-28

    Critical building blocks for the response to HIV were made until 2012 despite a series of political, social and financial challenges. A rapid increase of HIV service coverage was observed from 2012 to 2015 through collaborative efforts of government and non-governmental organisations (NGOs). Government facilities, in particular, demonstrated their capacity to expand services for antiretroviral therapy (ART), prevention of mother-to-child transmission (PMTCT) of HIV, tuberculosis and HIV co-infection and methadone-maintenance therapy (MMT). After nearly three decades into the response to HIV, Myanmar has adopted strategies to provide the right interventions to the right people in the right places to maximise impact and cost efficiency. In particular, the country is now using strategic information to classify areas into high-, medium- and low-HIV burden and risk of new infections for geographical prioritisation - as HIV remains concentrated among key population (KP) groups in specific geographical areas. Ways forward include: •Addressing structural barriers for KP to access services, and identifying and targeting KPs at higher risk;•Strengthening the network of public facilities, NGOs and general practitioners and introducing a case management approach to assist KPs and other clients with unknown HIV status, HIV-negative clients and newly diagnosed clients to access the health services across the continuum to increase the number of people testing for HIV and to reduce loss to follow-up in both prevention and treatment;•Increasing the availability of HIV testing and counselling services for KPs, clients of female sex workers (FSW), and other populations at risk, and raising the demand for timely testing including expansion of outreach and client-initiated voluntary counselling and testing (VCT) services;•Monitoring and maximising retention from HIV diagnosis to ART initiation and expanding quality HIV laboratory services, especially viral load

  6. HIV and Pregnancy

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG HIV and Pregnancy Home For Patients Search FAQs HIV ... HIV and Pregnancy FAQ113, July 2017 PDF Format HIV and Pregnancy Pregnancy What is human immunodeficiency virus ( ...

  7. Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA

    OpenAIRE

    Friew, Yeshitila N; Boyko, Vitaly; Hu, Wei-Shau; Pathak, Vinay K

    2009-01-01

    Abstract Background Host restriction factor APOBEC3G (A3G) blocks human immunodeficiency virus type 1 (HIV-1) replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC) to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Ga...

  8. HIV diagnosis, linkage to HIV care, and HIV risk behaviors among newly diagnosed HIV-positive female sex workers in Kigali, Rwanda

    NARCIS (Netherlands)

    Braunstein, Sarah L.; Umulisa, Marie-Michèle; Veldhuijzen, Nienke J.; Kestelyn, Evelyne; Ingabire, Chantal M.; Nyinawabega, Jeanine; van de Wijgert, Janneke H. H. M.; Nash, Denis

    2011-01-01

    To evaluate linkage-to-care, sexual behavior change, and psychosocial experiences among newly HIV-diagnosed female sex workers (FSWs) in Rwanda. FSWs (n = 800) with unknown serostatus were screened for HIV during 2007/2008. Women testing HIV positive (n = 192) were referred to care and asked to

  9. Lignosulfonic acid exhibits broadly anti-HIV-1 activity--potential as a microbicide candidate for the prevention of HIV-1 sexual transmission.

    Directory of Open Access Journals (Sweden)

    Min Qiu

    Full Text Available Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV, herpes simplex virus (HSV, Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA, a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide.

  10. HIV and AIDS

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español HIV and AIDS KidsHealth / For Kids / HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

  11. Interaction of small molecule inhibitors of HIV-1 entry with CCR5

    International Nuclear Information System (INIS)

    Seibert, Christoph; Ying Weiwen; Gavrilov, Svetlana; Tsamis, Fotini; Kuhmann, Shawn E.; Palani, Anandan; Tagat, Jayaram R.; Clader, John W.; McCombie, Stuart W.; Baroudy, Bahige M.; Smith, Steven O.; Dragic, Tatjana; Moore, John P.; Sakmar, Thomas P.

    2006-01-01

    The CC-chemokine receptor 5 (CCR5) is the major coreceptor for macrophage-tropic (R5) HIV-1 strains. Several small molecule inhibitors of CCR5 that block chemokine binding and HIV-1 entry are being evaluated as drug candidates. Here we define how CCR5 antagonists TAK-779, AD101 (SCH-350581) and SCH-C (SCH-351125), which inhibit HIV-1 entry, interact with CCR5. Using a mutagenesis approach in combination with a viral entry assay to provide a direct functional read out, we tested predictions based on a homology model of CCR5 and analyzed the functions of more than 30 amino acid residues. We find that a key set of aromatic and aliphatic residues serves as a hydrophobic core for the ligand binding pocket, while E283 is critical for high affinity interaction, most likely by acting as the counterion for a positively charged nitrogen atom common to all three inhibitors. These results provide a structural basis for understanding how specific antagonists interact with CCR5, and may be useful for the rational design of new, improved CCR5 ligands

  12. The preclinical discovery and development of dolutegravir for the treatment of HIV.

    Science.gov (United States)

    Bailly, Fabrice; Cotelle, Philippe

    2015-01-01

    Integration of the viral genome into the host cell chromatin is a central step in the replication cycle of HIV. Blocking the viral integrase (IN) enzyme therefore provides an attractive therapeutic strategy, as evidenced by the recent clinical approval of three IN strand transfer inhibitors. Dolutegravir is a therapy that is unique in its ability to evade HIV drug resistance in treatment-naïve patients. This review starts by providing a brief summary of the history of HIV-1 IN inhibitors. The authors follow this with details of the discovery and preclinical and clinical developments of dolutegravir. Finally, the authors provide details of dolutegravir's post-launch including the launch of the combination pill of dolutegravir, abacavir and lamivudine in August 2014. The launch of raltegravir, the first IN inhibitor from Merck & Co., has created new hopes for the patient. Indeed, pharmaceutical companies have not lost courage by attempting to address the major drawbacks of this first-in-class molecule. And while the drug elvitegravir has been inserted into a four-drug combination pill providing a once-daily dosing alternative, dolutegravir has demonstrated superiority in terms of its efficacy and resistance.

  13. The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection

    Directory of Open Access Journals (Sweden)

    Assunta Venuti

    2017-10-01

    Full Text Available The CC chemokine receptor 5 (CCR5 is responsible for immune and inflammatory responses by mediation of chemotactic activity in leukocytes, although it is expressed on different cell types. It has been shown to act as co-receptor for the human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV. Natural reactive antibodies (Abs recognizing first loop (ECL1 of CCR5 have been detected in several pools of immunoglobulins from healthy donors and from several cohorts of either HIV-exposed but uninfected subjects (ESN or HIV-infected individuals who control disease progression (LTNP as well. The reason of development of anti-CCR5 Abs in the absence of autoimmune disease is still unknown; however, the presence of these Abs specific for CCR5 or for other immune receptors and mediators probably is related to homeostasis maintenance. The majority of anti-CCR5 Abs is directed to HIV binding site (N-terminus and ECL2 of the receptor. Conversely, it is well known that ECL1 of CCR5 does not bind HIV; thus, the anti-CCR5 Abs directed to ECL1 elicit a long-lasting internalization of CCR5 but not interfere with HIV binding directly; these Abs block HIV infection in either epithelial cells or CD4+ T lymphocytes and the mechanism differs from those ones described for all other CCR5-specific ligands. The Ab-mediated CCR5 internalization allows the formation of a stable signalosome by interaction of CCR5, β-arrestin2 and ERK1 proteins. The signalosome degradation and the subsequent de novo proteins synthesis determine the CCR5 reappearance on the cell membrane with a very long-lasting kinetics (8 days. The use of monoclonal Abs to CCR5 with particular characteristics and mode of action may represent a novel mode to fight viral infection in either vaccinal or therapeutic strategies.

  14. HIV status awareness, partnership dissolution and HIV transmission in generalized epidemics.

    Science.gov (United States)

    Reniers, Georges; Armbruster, Benjamin

    2012-01-01

    HIV status aware couples with at least one HIV positive partner are characterized by high separation and divorce rates. This phenomenon is often described as a corollary of couples HIV Testing and Counseling (HTC) that ought to be minimized. In this contribution, we demonstrate the implications of partnership dissolution in serodiscordant couples for the propagation of HIV. We develop a compartmental model to study epidemic outcomes of elevated partnership dissolution rates in serodiscordant couples and parameterize it with estimates from population-based data (Rakai, Uganda). Via its effect on partnership dissolution, every percentage point increase in HIV status awareness reduces HIV incidence in monogamous populations by 0.27 percent for women and 0.63 percent for men. These effects are even larger when the assumption of monogamy can be relaxed, but are moderated by other behavior changes (e.g., increased condom use) in HIV status aware serodiscordant partnerships. When these behavior changes are taken into account, each percentage point increase in HIV status awareness reduces HIV incidence by 0.13 and 0.32 percent for women and men, respectively (assuming monogamy). The partnership dissolution effect exists because it decreases the fraction of serodiscordant couples in the population and prolongs the time that individuals spend outside partnerships. Our model predicts that elevated partnership dissolution rates in HIV status aware serodiscordant couples reduce the spread of HIV. As a consequence, the full impact of couples HTC for HIV prevention is probably larger than recognized to date. Particularly high partnership dissolution rates in female positive serodiscordant couples contribute to the gender imbalance in HIV infections.

  15. HIV Risk and Prevention

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Risk and Prevention Recommend on Facebook Tweet Share ...

  16. HIV stigma and social capital in women living with HIV

    OpenAIRE

    Cuca, Yvette P.; Asher, Alice; Okonsky, Jennifer; Kaihura, Alphoncina; Dawson-Rose, Carol; Webel, Allison

    2016-01-01

    Women living with HIV (WLWH) continue to experience HIV-related stigma. Social capital is one resource that could mitigate HIV stigma. Our cross-sectional study examined associations between social capital and HIV-related stigma in 135 WLWH in the San Francisco Bay Area. The mean age of study participants was 48 years; 60% were African American; 29% had less than a high school education; and 19% were employed. Age was significantly associated with perceived HIV stigma (p = .001), but total so...

  17. Ethnic Comparisons in HIV Testing Attitudes, HIV Testing, and Predictors of HIV Testing Among Black and White College Students.

    Science.gov (United States)

    Moore, Melanie P; Javier, Sarah J; Abrams, Jasmine A; McGann, Amanda Wattenmaker; Belgrave, Faye Z

    2017-08-01

    This study's primary aim was to examine ethnic differences in predictors of HIV testing among Black and White college students. We also examined ethnic differences in sexual risk behaviors and attitudes toward the importance of HIV testing. An analytic sample of 126 Black and 617 White undergraduatestudents aged 18-24 were analyzed for a subset of responses on the American College Health Association-National College Health Assessment II (ACHA-NCHA II) (2012) pertaining to HIV testing, attitudes about the importance of HIV testing, and sexual risk behaviors. Predictors of HIV testing behavior were analyzed using logistic regression. t tests and chi-square tests were performed to access differences in HIV test history, testing attitudes, and sexual risk behaviors. Black students had more positive attitudes toward testing and were more likely to have been tested for HIV compared to White students. A greater number of sexual partners and more positive HIV testing attitudes were significant predictors of HIV testing among White students, whereas relationship status predicted testing among Black students. Older age and history of ever having sex were significant predictors of HIV testing for both groups. There were no significant differences between groups in number of sexual partners or self-reports in history of sexual experience (oral, vaginal, or anal). Factors that influence HIV testing may differ across racial/ethnic groups. Findings support the need to consider racial/ethnic differences in predictors of HIV testing during the development and tailoring of HIV testing prevention initiatives targeting college students.

  18. Improving comprehension and recall of information for an HIV vaccine trial among women at risk for HIV: reading level simplification and inclusion of pictures to illustrate key concepts.

    Science.gov (United States)

    Murphy, D A; O'Keefe, Z H; Kaufman, A H

    1999-10-01

    A simplified version of the prototype HIV vaccine material was developed through (a) reducing reading grade level, (b) restructuring of the organization and categorization of the material, (c) adding pictures designed to emphasize key concepts, and (d) obtaining feedback on the simplified version through focus groups with the target population. Low-income women at risk for HIV (N = 141) recruited from a primary care clinic were randomly assigned to be presented the standard or the simplified version. There were no significant differences between the groups in terms of education or Vocabulary, Block Design, and Passage Comprehension scores. Women who received the simplified version had significantly higher comprehension scores immediately following presentation of the material than did women who received the standard version and were also significantly more likely to recall study benefits and risks. These findings were maintained at 3-month follow-up. Implications for informed consent are discussed.

  19. Does provider-initiated HIV testing and counselling lead to higher HIV testing rate and HIV case finding in Rwandan clinics?

    NARCIS (Netherlands)

    Kayigamba, Felix R.; van Santen, Daniëla; Bakker, Mirjam I.; Lammers, Judith; Mugisha, Veronicah; Bagiruwigize, Emmanuel; de Naeyer, Ludwig; Asiimwe, Anita; Schim van der Loeff, Maarten F.

    2016-01-01

    Provider-initiated HIV testing and counselling (PITC) is promoted as a means to increase HIV case finding. We assessed the effectiveness of PITC to increase HIV testing rate and HIV case finding among outpatients in Rwandan health facilities (HF). PITC was introduced in six HFs in 2009-2010. HIV

  20. The Times, They are a-Changing: HOPE for HIV-to-HIV Organ Transplantation.

    Science.gov (United States)

    Haidar, Ghady; Singh, Nina

    2017-09-01

    HIV-infected persons who achieve undetectable viral loads on antiretroviral therapy currently have near-normal lifespans. Liver disease is a major cause of non-AIDS-related deaths, and as a result of longer survival, the prevalence of end-stage renal disease in HIV is increasing. HIV-infected persons undergoing organ transplantation generally achieve comparable patient and graft survival rates compared to their HIV-uninfected counterparts, despite a nearly threefold increased risk of acute rejection. However, the ongoing shortage of suitable organs can limit transplantation as an option, and patients with HIV have higher waitlist mortality than others. One way to solve this problem would be to expand the donor pool to include HIV-infected individuals. The results of a South Africa study involving 27 HIV-to-HIV kidney transplants showed promise, with 3- and 5-year patient and graft survival rates similar to those of their HIV-uninfected counterparts. Similarly, individual cases of HIV-to-HIV liver transplantation from the United Kingdom and Switzerland have also shown good results. In the United States, HIV-to-HIV kidney and liver transplants are currently permitted only under a research protocol. Nevertheless, areas of ambiguity exist, including streamlining organ allocation practices, optimizing HIV-infected donor and recipient selection, managing donor-derived transmission of a resistant HIV strain, determining optimal immunosuppressive and antiretroviral regimens, and elucidating the incidence of rejection in HIV-to-HIV solid organ transplant recipients.

  1. The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Daniëlle van Manen

    2008-02-01

    Full Text Available The antiviral factor tripartite interaction motif 5alpha (Trim5alpha restricts a broad range of retroviruses in a species-specific manner. Although human Trim5alpha is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q were shown to affect the antiviral activity of Trim5alpha in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5alpha that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4 HIV-1 variants and when a viral load of 10(4.5 copies per ml plasma was used as an endpoint in survival analysis. Interestingly, naive CD4 T cells, which are selectively targeted by X4 HIV-1, revealed a significantly higher expression of Trim5alpha than memory CD4 T cells. In addition, we observed that the 136Q allele in combination with the -2GG genotype in the 5'UTR was associated with an accelerated disease progression. Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5alpha on HIV-1 in vivo.

  2. The Effect of Trim5 Polymorphisms on the Clinical Course of HIV-1 Infection

    Science.gov (United States)

    van Manen, Daniëlle; Rits, Maarten A. N; Beugeling, Corrine; van Dort, Karel; Schuitemaker, Hanneke; Kootstra, Neeltje A

    2008-01-01

    The antiviral factor tripartite interaction motif 5α (Trim5α) restricts a broad range of retroviruses in a species-specific manner. Although human Trim5α is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q) were shown to affect the antiviral activity of Trim5α in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5α that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4) HIV-1 variants and when a viral load of 104.5 copies per ml plasma was used as an endpoint in survival analysis. Interestingly, naive CD4 T cells, which are selectively targeted by X4 HIV-1, revealed a significantly higher expression of Trim5α than memory CD4 T cells. In addition, we observed that the 136Q allele in combination with the −2GG genotype in the 5′UTR was associated with an accelerated disease progression. Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5α on HIV-1 in vivo. PMID:18248091

  3. HIV/AIDS

    Science.gov (United States)

    ... Key populations are groups who are at increased risk of HIV irrespective of epidemic type or local context. They include: men who have sex with men, ... HIV testing and counselling; HIV treatment and care; risk-reduction ... management of STIs, tuberculosis and viral hepatitis. Elimination of ...

  4. HIV status awareness, partnership dissolution and HIV transmission in generalized epidemics.

    Directory of Open Access Journals (Sweden)

    Georges Reniers

    Full Text Available HIV status aware couples with at least one HIV positive partner are characterized by high separation and divorce rates. This phenomenon is often described as a corollary of couples HIV Testing and Counseling (HTC that ought to be minimized. In this contribution, we demonstrate the implications of partnership dissolution in serodiscordant couples for the propagation of HIV.We develop a compartmental model to study epidemic outcomes of elevated partnership dissolution rates in serodiscordant couples and parameterize it with estimates from population-based data (Rakai, Uganda.Via its effect on partnership dissolution, every percentage point increase in HIV status awareness reduces HIV incidence in monogamous populations by 0.27 percent for women and 0.63 percent for men. These effects are even larger when the assumption of monogamy can be relaxed, but are moderated by other behavior changes (e.g., increased condom use in HIV status aware serodiscordant partnerships. When these behavior changes are taken into account, each percentage point increase in HIV status awareness reduces HIV incidence by 0.13 and 0.32 percent for women and men, respectively (assuming monogamy. The partnership dissolution effect exists because it decreases the fraction of serodiscordant couples in the population and prolongs the time that individuals spend outside partnerships.Our model predicts that elevated partnership dissolution rates in HIV status aware serodiscordant couples reduce the spread of HIV. As a consequence, the full impact of couples HTC for HIV prevention is probably larger than recognized to date. Particularly high partnership dissolution rates in female positive serodiscordant couples contribute to the gender imbalance in HIV infections.

  5. Prevalence and characteristics of HIV/HBV and HIV/HCV coinfections in Tuscany

    Directory of Open Access Journals (Sweden)

    Monia Puglia

    2016-07-01

    Conclusions: We have observed less advanced disease in HIV and HCV-HIV patients compared with HBV–HIV coinfected patients. Moreover, our results show a higher prevalence of HIV/HCV among drug addicts and in the age-group 35–59, corresponding to those born in years considered most at risk for addiction. This study also confirms the finding of a less advanced HIV disease in HIV/HCV coinfected patients.

  6. Quantitative analyses reveal distinct sensitivities of the capture of HIV-1 primary viruses and pseudoviruses to broadly neutralizing antibodies.

    Science.gov (United States)

    Kim, Jiae; Jobe, Ousman; Peachman, Kristina K; Michael, Nelson L; Robb, Merlin L; Rao, Mangala; Rao, Venigalla B

    2017-08-01

    Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. HIV stigma and social capital in women living with HIV

    Science.gov (United States)

    Cuca, Yvette P.; Asher, Alice; Okonsky, Jennifer; Kaihura, Alphoncina; Dawson-Rose, Carol; Webel, Allison

    2016-01-01

    Women living with HIV (WLWH) continue to experience HIV-related stigma. Social capital is one resource that could mitigate HIV stigma. Our cross-sectional study examined associations between social capital and HIV-related stigma in 135 WLWH in the San Francisco Bay Area. The mean age of study participants was 48 years; 60% were African American; 29% had less than a high school education; and 19% were employed. Age was significantly associated with perceived HIV stigma (p = .001), but total social capital was not. Women with lower Value of Life social capital scores had significantly higher total stigma scores (p = .010) and higher Negative Self-image stigma scores (p = .001). Women who felt less valued in their social worlds may have been more likely to perceive HIV stigma, which could have negative health consequences. This work begins to elucidate the possible relationships between social capital and perceived HIV stigma. PMID:27697368

  8. HIV, violence, blame and shame: pathways of risk to internalized HIV stigma among South African adolescents living with HIV.

    Science.gov (United States)

    Pantelic, Marija; Boyes, Mark; Cluver, Lucie; Meinck, Franziska

    2017-08-21

    Internalized HIV stigma is a key risk factor for negative outcomes amongst adolescents living with HIV (ALHIV), including non-adherence to anti-retroviral treatment, loss-to-follow-up and morbidity. This study tested a theoretical model of multi-level risk pathways to internalized HIV stigma among South African ALHIV. From 2013 to 2015, a survey using t otal population sampling of ALHIV who had ever initiated anti-retroviral treatment (ART) in 53 public health facilities in the Eastern Cape, South Africa was conducted. Community-tracing ensured inclusion of ALHIV who were defaulting from ART or lost to follow-up. 90.1% of eligible ALHIV were interviewed ( n  = 1060, 55% female, mean age = 13.8, 21% living in rural locations). HIV stigma mechanisms (internalized, enacted, and anticipated), HIV-related disability, violence victimization (physical, emotional, sexual abuse, bullying victimization) were assessed using well-validated self-report measures. Structural equation modelling was used to test a theoretically informed model of risk pathways from HIV-related disability to internalized HIV stigma. The model controlled for age, gender and urban/rural address. Prevalence of internalized HIV stigma was 26.5%. As hypothesized, significant associations between internalized stigma and anticipated stigma, as well as depression were obtained. Unexpectedly, HIV-related disability, victimization, and enacted stigma were not directly associated with internalized stigma. Instead significant pathways were identified via anticipated HIV stigma and depression. The model fitted the data well (RMSEA = .023; CFI = .94; TLI = .95; WRMR = 1.070). These findings highlight the complicated nature of internalized HIV stigma. Whilst it is seemingly a psychological process, indirect pathways suggest multi-level mechanisms leading to internalized HIV stigma. Findings suggest that protection from violence within homes, communities and schools may interrupt risk pathways from HIV

  9. Missed opportunities for HIV control: Gaps in HIV testing for partners of people living with HIV in Lima, Peru.

    Directory of Open Access Journals (Sweden)

    Ana L Vasquez

    Full Text Available Based on the hypothesis that HIV programs struggle to deliver health services that harmonize necessities of treatment and prevention, we described the outcomes of routinely provided HIV testing to partners of people living with HIV (PLWH through a secondary analysis of routine data collected at a public hospital in Lima, Peru.Among PLWH enrolled in the study center's HIV program between 2005 and 2014, we identified index cases (IC: PLWH who reported a unique partner not previously enrolled. We grouped partners according to their HIV status as reported by IC and collected data on HIV testing, clinical characteristics and admissions. The main outcome was the frequency of HIV testing among partners with reported unknown/seronegative HIV status.Out of 1586 PLWH who reported a unique partner at enrollment, 171 had a previously enrolled partner, leaving 1415 (89% IC. HIV status of the partner was reported as unknown in 571 (40%, seronegative in 325 (23% and seropositive in 519 (37%. Out of 896 partners in the unknown/seronegative group, 72 (8% had HIV testing, 42/72 (58% tested within three months of IC enrollment. Among the 49/72 (68% who tested positive for HIV, 33 (67% were enrolled in the HIV program. The proportion in WHO clinical stage IV was lower in enrolled partners compared to IC (37% vs 9%, p = 0.04. Non-tested partners (824 were likely reachable by the hospital, as 297/824 (36% of their IC were admitted in the study center at least once, 51/243 (21% female IC had received pregnancy care at the study center, and 401/692 (64% of IC on antiretroviral therapy had achieved viral suppression, implying frequent visits to the hospital for pill pick-up.In this setting, HIV testing of partners of PLWH was suboptimal, illustrating missed opportunities for HIV control. Integration of HIV strategies in primarily clinical-oriented services is a challenging need.

  10. HIV Viral Load

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  11. Increasing rates of obesity among HIV-infected persons during the HIV epidemic.

    Directory of Open Access Journals (Sweden)

    Nancy Crum-Cianflone

    2010-04-01

    Full Text Available The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV-infected persons are unknown.We evaluated prospective data from a U.S. Military HIV Natural History Study (1985-2004 consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models.Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05. The majority of patients (62% gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05. Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era.HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care.

  12. Minimum description length block finder, a method to identify haplotype blocks and to compare the strength of block boundaries.

    Science.gov (United States)

    Mannila, H; Koivisto, M; Perola, M; Varilo, T; Hennah, W; Ekelund, J; Lukk, M; Peltonen, L; Ukkonen, E

    2003-07-01

    We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the significance of each block boundary. We have applied the method to the published data of Daly and colleagues. The results expose some problems that exist in the current methods for the evaluation of the significance of predicted block boundaries. Our method, MDL block finder, can be used to compare block borders in different sample sets, and we demonstrate this by applying the MDL-based method to define the block structure in chromosomes from population isolates.

  13. HIV RNA and proviral HIV DNA can be detected in semen after 6 months of antiretroviral therapy although HIV RNA is undetectable in blood.

    Science.gov (United States)

    Du, Peiwei; Liu, An; Jiao, Yanmei; Liu, Cuie; Jiang, Taiyi; Zhu, Weijun; Zhu, Yunxia; Wu, Hao; Sun, Lijun

    2016-03-01

    The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV-infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV-infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV-infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real-time PCR. The C2-V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co-receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV-infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

  14. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    Directory of Open Access Journals (Sweden)

    Pichili Vijaya Bhaskar Reddy

    2012-01-01

    Full Text Available HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB. Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population.

  15. Chorioamnionitis in pregnancy: a comparative study of HIV-positive and HIV-negative parturients.

    Science.gov (United States)

    Ocheke, Amaka N; Agaba, Patricia A; Imade, Godwin E; Silas, Olugbenga A; Ajetunmobi, Olanrewaju I; Echejoh, Godwins; Ekere, Clement; Sendht, Ayuba; Bitrus, James; Agaba, Emmanuel I; Sagay, Atiene S

    2016-03-01

    Chorioamnionitis is an important risk factor for vertical transmission of HIV/AIDS. We compared the prevalence and correlates of histologic chorioamnionitis (HCA) in HIV-positive and HIV-negative pregnant women. HIV-positive and -negative parturients were interviewed, examined and had their placentas examined histologically for chorioamnionitis. Data regarding HIV were also retrieved from their hospital records. A total of 298 parturients (150 HIV positive and 148 HIV negative) were enrolled. The two groups were similar in socio-demographic and obstetric parameters except for age. The prevalence of HCA was 57.1% in HIV-positive women and 61.6% in HIV-negative women (p = 0.43). HCA staging was associated with the number of intrapartum vaginal examinations in HIV-positive subjects and nulliparity in HIV-negative subjects. The number of intrapartum vaginal examinations and coitus in the week prior to delivery significantly affected the grade of HCA in HIV-negative subjects. The prevalence of HCA in both HIV-positive and HIV-negative is high. Most variables did not affect the occurrence of HCA in both groups studied except number of intrapartum examinations, coitus in the preceding one week and nulliparity, which were related to severity of the disease. © The Author(s) 2016.

  16. Risk Factors for HIV Transmission and Barriers to HIV Disclosure: Metropolitan Atlanta Youth Perspectives.

    Science.gov (United States)

    Camacho-Gonzalez, Andres F; Wallins, Amy; Toledo, Lauren; Murray, Ashley; Gaul, Zaneta; Sutton, Madeline Y; Gillespie, Scott; Leong, Traci; Graves, Chanda; Chakraborty, Rana

    2016-01-01

    Youth carry the highest incidence of HIV infection in the United States. Understanding adolescent and young adult (AYA) perspectives on HIV transmission risk is important for targeted HIV prevention. We conducted a mixed methods study with HIV-infected and uninfected youth, ages 18-24 years, from Atlanta, GA. We provided self-administered surveys to HIV-infected and HIV-uninfected AYAs to identify risk factors for HIV acquisition. By means of computer-assisted thematic analyses, we examined transcribed focus group responses on HIV education, contributors to HIV transmission, and pre-sex HIV status disclosure. The 68 participants had the following characteristics: mean age 21.5 years (standard deviation: 1.8 years), 85% male, 90% black, 68% HIV-infected. HIV risk behaviors included the perception of condomless sex (Likert scale mean: 8.0) and transactional sex (88% of participants); no differences were noted by HIV status. Qualitative analyses revealed two main themes: (1) HIV risk factors among AYAs, and (2) barriers to discussing HIV status before sex. Participants felt the use of social media, need for immediate gratification, and lack of concern about HIV disease were risk factors for AYAs. Discussing HIV status with sex partners was uncommon. Key reasons included: fear of rejection, lack of confidentiality, discussion was unnecessary in temporary relationships, and disclosure negatively affecting the mood. HIV prevention strategies for AYAs should include improving condom use frequency and HIV disclosure skills, responsible utilization of social media, and education addressing HIV prevention including the risks of transactional sex.

  17. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  18. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

    Science.gov (United States)

    Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P; Gottlieb, Geoffrey S; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d'Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N'gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Ostergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-Gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; Pac-Ci; Abidjan

    2013-01-01

    HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region. Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7) and 42.4 years, IQR (37.0-47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm(3), IQR (83-247) among HIV-2 infected patients and 146 cells/mm(3), IQR (55-249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3) after 24 months on ART for HIV-2 patients and 169 cells/mm(3) for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3). This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

  19. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

    Directory of Open Access Journals (Sweden)

    Didier K Ekouevi

    Full Text Available HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA.We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region.Data was merged for 1,754 patients (56% female, including 1,021 HIV-2 infected patients (551 on ART and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART. At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7 and 42.4 years, IQR (37.0-47.3 for dually seropositive patients (p = 0.048. Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C. The median CD4 count at the ART initiation is 166 cells/mm(3, IQR (83-247 among HIV-2 infected patients and 146 cells/mm(3, IQR (55-249 among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3 after 24 months on ART for HIV-2 patients and 169 cells/mm(3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3.This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

  20. High HIV Prevalence, Suboptimal HIV Testing, and Low Knowledge of HIV-Positive Serostatus Among Injection Drug Users in St. Petersburg, Russia

    Science.gov (United States)

    Toussova, Olga V.; Verevochkin, Sergei V.; Barbour, Russell; Heimer, Robert; Kozlov, Andrei P.

    2011-01-01

    The purpose of this analysis was to estimate human immunodeficiency virus (HIV) prevalence and testing patterns among injection drug users (IDUs) in St. Petersburg, Russia. HIV prevalence among 387 IDUs in the sample was 50%. Correlates of HIV-positive serostatus included unemployment, recent unsafe injections, and history/current sexually transmitted infection. Seventy-six percent had been HIV tested, but only 22% of those who did not report HIV-positive serostatus had been tested in the past 12 months and received their test result. Correlates of this measure included recent doctor visit and having been in prison or jail among men. Among the 193 HIV-infected participants, 36% were aware of their HIV-positive serostatus. HIV prevalence is high and continuing to increase in this population. Adequate coverage of HIV testing has not been achieved, resulting in poor knowledge of positive serostatus. Efforts are needed to better understand motivating and deterring factors for HIV testing in this setting. PMID:18843531

  1. Kaposi Sarcoma among HIV Infected Patients in Lagos University Teaching Hospital, Nigeria: A 14-Year Retrospective Clinicopathological Study

    Directory of Open Access Journals (Sweden)

    Olakanmi Akinde

    2016-01-01

    Full Text Available Background. Despite the increased incidence of Kaposi sarcoma (KS resulting from the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS pandemic, there is still significant underreporting of KS in this environment. Objectives. This study was aimed at determining the incidence and clinicopathologic patterns of KS among HIV infected patients in Lagos University Teaching Hospital (LUTH, Nigeria, over a 14-year period: January 2000 to December 2013. Methodology. The materials for this study included patients’ hospital clinical files, duplicate copies of histopathologic reports, and tissue blocks and corresponding archival slides in the Anatomic and Molecular Pathology Department and the HIV/AIDS unit of the Department of Haematology. Results. Within the study period, 182 cases of KS were diagnosed, accounting for 1.2% of all patients managed for HIV/AIDS and 2.99% of solid malignant tumours. The male-to-female ratio and modal age group were 1 : 1.3 and 5th decade, respectively. Most cases (90% had purely mucocutaneous involvement with the lower limb being the commonest site (65.8%. The majority of lesions were plaques (65.8%. Vascular formation was the predominant histologic type seen (43.5%. Conclusion. KS in Lagos followed the same epidemiologic trend as other centers in Nigeria, with an increasing incidence in this era of HIV/AIDS.

  2. Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1.

    Science.gov (United States)

    Telwatte, Sushama; Moore, Katie; Johnson, Adam; Tyssen, David; Sterjovski, Jasminka; Aldunate, Muriel; Gorry, Paul R; Ramsland, Paul A; Lewis, Gareth R; Paull, Jeremy R A; Sonza, Secondo; Tachedjian, Gilda

    2011-06-01

    Topical microbicides for use by women to prevent the transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. SPL7013 is a dendrimer with broad-spectrum activity against HIV type I (HIV-1) and -2 (HIV-2), herpes simplex viruses type-1 (HSV-1) and -2 (HSV-2) and human papillomavirus. SPL7013 [3% (w/w)] has been formulated in a mucoadhesive carbopol gel (VivaGel®) for use as a topical microbicide. Previous studies showed that SPL7013 has similar potency against CXCR4-(X4) and CCR5-using (R5) strains of HIV-1 and that it blocks viral entry. However, the ability of SPL7013 to directly inactivate HIV-1 is unknown. We examined whether SPL7013 demonstrates virucidal activity against X4 (NL4.3, MBC200, CMU02 clade EA and 92UG046 clade D), R5 (Ba-L, NB25 and 92RW016 clade A) and dual-tropic (R5X4; MACS1-spln) HIV-1 using a modified HLA-DR viral capture method and by polyethylene glycol precipitation. Evaluation of virion integrity was determined by ultracentrifugation through a sucrose cushion and detection of viral proteins by Western blot analysis. SPL7013 demonstrated potent virucidal activity against X4 and R5X4 strains, although virucidal activity was less potent for the 92UG046 X4 clade D isolate. Where potent virucidal activity was observed, the 50% virucidal concentrations were similar to the 50% effective concentrations previously reported in drug susceptibility assays, indicating that the main mode of action of SPL7013 is by direct viral inactivation for these strains. In contrast, SPL7013 lacked potent virucidal activity against R5 HIV-1 strains. Evaluation of the virucidal mechanism showed that SPL7013-treated NL4.3, 92UG046 and MACS1-spln virions were intact with no significant decrease in gp120 surface protein with respect to p24 capsid content compared to the corresponding untreated virus. These studies demonstrate that SPL

  3. HIV Structural Database

    Science.gov (United States)

    SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

  4. Correlates of injecting in an HIV incidence hotspot among substance users in Tijuana, Mexico.

    Science.gov (United States)

    Kori, Nana; Roth, Alexis M; Lozada, Remedios; Vera, Alicia; Brouwer, Kimberly C

    2014-05-01

    Substance use and HIV are growing problems in the Mexico-U.S. border city of Tijuana, a sex tourism destination situated on a northbound drug trafficking route. In a previous longitudinal study of injection drug users (IDUs), we found that >90% of incident HIV cases occurred within an 'HIV incidence hotspot,' consisting of 2.5-blocks. This study examines behavioral, social, and environmental correlates associated with injecting in this HIV hotspot. From 4/06 to 6/07, IDUs aged ≥18 years were recruited using respondent-driven sampling. Participants underwent antibody testing for HIV and syphilis and interviewer-administered surveys eliciting information on demographics, drug use, sexual behaviors, and socio-environmental influences. Participants were defined as injecting in the hotspot if they most frequently injected within a 3 standard deviational ellipse of the cohort's incident HIV cases. Logistic regression was used to identify individual and structural factors associated with the HIV 'hotspot'. Of 1031 IDUs, the median age was 36 years; 85% were male; HIV prevalence was 4%. As bivariate analysis indicated different correlates for males and females, models were stratified by sex. Factors independently associated with injecting in the HIV hotspot for male IDUs included homelessness (AOR 1.72; 95%CI 1.14-2.6), greater intra-urban mobility (AOR 3.26; 95%CI 1.67-6.38), deportation (AOR 1.58; 95%CI 1.18-2.12), active syphilis (AOR 3.03; 95%CI 1.63-5.62), needle sharing (AOR 0.57; 95%CI 0.42-0.78), various police interactions, perceived HIV infection risk (AOR 1.52; 95%CI 1.13-2.03), and health insurance status (AOR 0.53; 95%CI 0.33-0.87). For female IDUs, significant factors included sex work (AOR 8.2; 95%CI 2.2-30.59), lifetime syphilis exposure (AOR 2.73; 95%CI 1.08-6.93), injecting inside (AOR 5.26; 95%CI 1.54-17.92), arrests for sterile syringe possession (AOR 4.87; 95%I 1.56-15.15), prior HIV testing (AOR 2.45; 95%CI 1.04-5.81), and health insurance status

  5. Nosocomial infections in HIV-infected and HIV-uninfected children ...

    African Journals Online (AJOL)

    One HIV-infected child died of varicella pneumonia. Other common nosocomial infections encountered in HIV-infected and HIV-uninfected children respectively were upper respiratory tract infections (pharyngitis, tonsillitis or rhinitis) affecting 21 and four, otitis media in five and one, oral candidiasis in seven and zero, urinary ...

  6. HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

    Science.gov (United States)

    Agarwal, Neeti; Iyer, Dinakar; Patel, Sanjeet G.; Sekhar, Rajagopal V.; Phillips, Terry M.; Schubert, Ulrich; Oplt, Toni; Buras, Eric D.; Samson, Susan L.; Couturier, Jacob; Lewis, Dorothy E.; Rodriguez-Barradas, Maria C.; Jahoor, Farook; Kino, Tomoshige; Kopp, Jeffrey B.; Balasubramanyam, Ashok

    2014-01-01

    Viral infections, such as HIV, have been linked to obesity, but mechanistic evidence that they cause adipose dysfunction in vivo is lacking. We investigated a pathogenic role for the HIV-1 accessory protein viral protein R (Vpr), which can coactivate the glucocorticoid receptor (GR) and co-repress peroxisome proliferator–activated receptor γ (PPARγ) in vitro, in HIV-associated adipose dysfunction. Vpr circulated in the blood of most HIV-infected patients tested, including those on antiretroviral therapy (ART) with undetectable viral load. Vpr-mediated mechanisms were dissected in vivo using mouse models expressing the Vpr transgene in adipose tissues and liver (Vpr-Tg) or infused with synthetic Vpr. Both models demonstrated accelerated whole-body lipolysis, hyperglycemia and hypertriglyceridemia, and tissue-specific findings. Fat depots in these mice had diminished mass, macrophage infiltration, and blunted PPARγ target gene expression but increased GR target gene expression. In liver, we observed blunted PPARα target gene expression, steatosis with decreased adenosine monophosphate– activated protein kinase activity, and insulin resistance. Similar to human HIV-infected patients, Vpr circulated in the serum of Vpr-Tg mice. Vpr blocked differentiation in preadipocytes through cell cycle arrest, whereas in mature adipocytes, it increased lipolysis with reciprocally altered association of PPARγ and GR with their target promoters. These results delineate a distinct pathogenic sequence: Vpr, released from HIV-1 in tissue reservoirs after ART, can disrupt PPAR/GR co-regulation and cell cycle control to produce adipose dysfunction and hepatosteatosis. Confirmation of these mechanisms in HIV patients could lead to targeted treatment of the metabolic complications with Vpr inhibitors, GR antagonists, or PPARγ/PPARα agonists. PMID:24285483

  7. Metabolic health across the BMI spectrum in HIV-infected and HIV-uninfected men.

    Science.gov (United States)

    Lake, Jordan E; Li, Xiuhong; Palella, Frank J; Erlandson, Kristine M; Wiley, Dorothy; Kingsley, Lawrence; Jacobson, Lisa P; Brown, Todd T

    2018-01-02

    In the general population, metabolic health often declines as BMI increases. However, some obese individuals maintain metabolic health. HIV and antiretroviral therapy have been associated with metabolic disturbances. We hypothesized that HIV-infected (HIV) men on suppressive antiretroviral therapy experience less metabolic health than HIV-uninfected (HIV) men across all BMI categories. In a cross-sectional analysis of 1018 HIV and 1092 HIV men enrolled in the multicenter AIDS cohort study, Poisson regression with robust variance determined associations between HIV serostatus and metabolic health prevalence (defined as meeting ≤2 of 5 National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria), adjusting for age, race, BMI category, smoking, and hepatitis C virus infection status. HIV men were younger (54 vs. 59 years) and had lower median BMI (25 vs. 27 kg/m). Nonobese HIV men had lower metabolic health prevalence than HIV men (BMI ≤25 kg/m: 80 vs. 94%, P BMI 25-29 kg/m: 64 vs. 71%, P = 0.05), but metabolic health prevalence among obese men did not differ by HIV serostatus (BMI 30-34 kg/m: 35 vs. 39%, P = 0.48; BMI ≥35 kg/m: 27 vs. 25%, P = 0.79). In the adjusted model, nonobese HIV men were less likely to demonstrate metabolic health than nonobese HIV men. Among HIV men, per year darunavir, zidovudine, and stavudine use were associated with lower metabolic health likelihood. Metabolically healthy obesity prevalence does not differ by HIV serostatus. However, among nonobese men, HIV infection is associated with lower metabolic health prevalence, with associations between lack of metabolic health and darunavir and thymidine analog nucleoside reverse transcriptase inhibitor exposure observed.

  8. Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

    International Nuclear Information System (INIS)

    Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi; Rhim, Hyangshuk; Bae, Yong Soo; Choi, Soo Young; Park, Jinseu

    2014-01-01

    HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction

  9. Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Gi Soo; Kwon, Dong-Joo; Ju, Sung Mi [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Rhim, Hyangshuk [Department of Biomedical Sciences, Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Bae, Yong Soo [Department of Biological Science, College of Natural Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Choi, Soo Young [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Park, Jinseu, E-mail: jinpark@hallym.ac.kr [Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2014-10-01

    HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes. - Highlights: • Celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory genes. • Celastrol inhibited HIV-1 Tat -induced activation of JNK MAPK. • Celastrol inhibited HIV-1 Tat-induced activation of both NF-κB and AP-1. • Celastrol inhibited HIV-1 Tat-induced inflammatory responses via HO-1 induction.

  10. Indikatorsygdomme for hiv-infektion

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Andersen, Åse Bengård; Koch, Anders

    2015-01-01

    The mortality of HIV-infected patients in Denmark approaches that of the background population. Still, half of the HIV-infected patients are diagnosed late, resulting in poorer response to therapy, larger cost and greater transmission rate. A pan-European initiative, "HIV in Europe" has published...... a guideline on indicator-based HIV testing in order to improve early HIV diagnosis. The Danish Society of Infectious Diseases wishes to highlight the importance of indicator-based HIV testing, in order to improve the possibility of early diagnosis and therapy of HIV-infection....

  11. Performance evaluation of the Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA, a 4th generation HIV assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2 in human serum or plasma.

    Science.gov (United States)

    Bentsen, Christopher; McLaughlin, Lisa; Mitchell, Elizabeth; Ferrera, Carol; Liska, Sally; Myers, Robert; Peel, Sheila; Swenson, Paul; Gadelle, Stephane; Shriver, M Kathleen

    2011-12-01

    A multi-center study was conducted to evaluate the Bio-Rad GS HIV Combo Ag/Ab EIA, a 4th generation HIV-1/HIV-2 assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2 in human serum or plasma in adult and pediatric populations. The objectives of the study were to assess assay performance for the detection of acute HIV infections; sensitivity in known HIV positive samples; percent agreement with HIV status; specificity in low and high risk individuals of unknown HIV status; and to compare assay performance to a 3rd generation HIV assay. The evaluation included testing 9150 samples at four U.S. clinical trial sites, using three kit lots. Unlinked samples were from routine testing, repositories or purchased from vendors. GS HIV Combo Ag/Ab EIA detection in samples from individuals in two separate populations with acute HIV infection was 95.2% (20/21) and 86.4% (38/44). Sensitivity was 100% (1603/1603) in known antibody positive [HIV-1 Groups M and O, and HIV-2] samples. HIV p24 antigen detection was 100% (53/53) in HIV-1 culture supernatants. HIV-1 seroconversion panel detection improved by a range of 0-20 days compared to a 3rd generation HIV test. Specificity was 99.9% (5989/5996) in low risk, 99.9% (959/960) in high risk and 100% (100/100) in pediatric populations. The GS HIV Combo Ag/Ab EIA significantly reduced the diagnostic window when compared to the 3rd generation screening assay, enabling earlier diagnosis of HIV infection. The performance parameters of the Bio-Rad GS HIV Combo Ag/Ab EIA are well suited for use in HIV diagnostic settings. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. New HIV Testing Algorithm: Promising Tool in the Fight Against HIV

    Centers for Disease Control (CDC) Podcasts

    2016-09-21

    In this podcast, CDC’s Dr. Phil Peters discusses the new HIV testing algorithm and how this latest technology can improve the diagnosis of acute HIV infection. Early detection of HIV is critical to saving lives, getting patients into treatment, and preventing transmission.  Created: 9/21/2016 by National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention (NCHHSTP), • Division of HIV/AIDS Prevention (DHAP).   Date Released: 9/21/2016.

  13. HIV Stigma and Unhealthy Alcohol Use Among People Living with HIV in Russia.

    Science.gov (United States)

    Lunze, Karsten; Lioznov, Dmitry; Cheng, Debbie M; Nikitin, Ruslan V; Coleman, Sharon M; Bridden, Carly; Blokhina, Elena; Krupitsky, Evgeny; Samet, Jeffrey H

    2017-09-01

    Unhealthy alcohol use, highly prevalent in the Russian Federation (Russia), is associated with HIV risk behaviors among people living with HIV (PLWH). HIV stigma contributes to the HIV risk environment in Russia. To examine HIV stigma among Russian PLWH and to explore its association with unhealthy alcohol use, we conducted a longitudinal analysis of 700 PLWH in St. Petersburg, Russia. We assessed the association between alcohol dependence and HIV stigma measured at baseline and 12 months follow-up. Participants with alcohol dependence (n = 446) reported significantly higher HIV stigma scores over time than those without dependence (n = 254) (adjusted mean difference 0.60, 95% CI 0.03-1.17; p = 0.04). In secondary analyses, we examined recent risky alcohol use and did not detect an association with HIV stigma. Alcohol dependence is associated with high HIV stigma among Russian PLWH but the nature of the association is conjectural. HIV prevention efforts in Russia that address alcohol use disorders hold potential to mitigate HIV-related stigma and its possible adverse effects among PLWH.

  14. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Sulggi A Lee

    Full Text Available A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the "reservoir". We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART.We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR; integrated DNA (Alu PCR; unspliced RNA (rtPCR, multiply-spliced RNA (TILDA, residual plasma HIV RNA (single copy PCR, and replication-competent virus (outgrowth assay. We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR. Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables.Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years, the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004 and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003. However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results.Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV during treatment.

  15. Psychiatric disorders, HIV infection and HIV/hepatitis co-infection in the correctional setting.

    Science.gov (United States)

    Baillargeon, J G; Paar, D P; Wu, H; Giordano, T P; Murray, O; Raimer, B G; Avery, E N; Diamond, P M; Pulvino, J S

    2008-01-01

    Psychiatric disorders such as bipolar disorder, schizophrenia and depression have long been associated with risk behaviors for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). The US prison population is reported to have elevated rates of HIV, hepatitis and most psychiatric disorders. This study examined the association of six major psychiatric disorders with HIV mono-infection, HIV/HCV co-infection and HIV/HBV co-infection in one of the nation's largest prison populations. The study population consisted of 370,511 Texas Department of Criminal Justice inmates who were incarcerated for any duration between January 1, 2003 and July 1, 2006. Information on medical conditions and sociodemographic factors was obtained from an institution-wide electronic medical information system. Offenders diagnosed with HIV mono-infection, HIV/HCV, HIV/HBV and all HIV combined exhibited elevated rates of major depression, bipolar disorder, schizophrenia, schizoaffective disorder, non-schizophrenic psychotic disorder and any psychiatric disorder. In comparison to offenders with HIV mono-infection, those with HIV/HCV co-infection had an elevated prevalence of any psychiatric disorder. This cross-sectional study's finding of positive associations between psychiatric disease and both HIV infection and hepatitis co-infection among Texas prison inmates holds both clinical and public health relevance. It will be important for future investigations to examine the extent to which psychiatric disorders serve as a barrier to medical care, communication with clinicians and adherence to prescribed medical regimens among both HIV-mono-infected and HIV/hepatitis-co-infected inmates.

  16. HIV Stigma and Social Capital in Women Living With HIV.

    Science.gov (United States)

    Cuca, Yvette P; Asher, Alice; Okonsky, Jennifer; Kaihura, Alphoncina; Dawson-Rose, Carol; Webel, Allison

    Women living with HIV (WLWH) continue to experience HIV-related stigma. Social capital is one resource that could mitigate HIV stigma. Our cross-sectional study examined associations between social capital and HIV-related stigma in 135 WLWH in the San Francisco Bay Area. The mean age of study participants was 48 years; 60% were African American; 29% had less than a high school education; and 19% were employed. Age was significantly associated with perceived HIV stigma (p = .001), but total social capital was not. Women with lower Value of Life social capital scores had significantly higher total stigma scores (p = .010) and higher Negative Self-image stigma scores (p = .001). Women who felt less valued in their social worlds may have been more likely to perceive HIV stigma, which could have negative health consequences. This work begins to elucidate the possible relationships between social capital and perceived HIV stigma. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  17. Get Tested for HIV

    Science.gov (United States)

    ... AIDS: What is HIV/AIDS? Women and HIV/AIDS Next section ... Tested? Why do I need to get tested for HIV? The only way to know if you have HIV is to get tested. Many people with HIV don’t have any symptoms. In the United States, about 1 in 7 ...

  18. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  19. MicroRNAs upregulated during HIV infection target peroxisome biogenesis factors: Implications for virus biology, disease mechanisms and neuropathology.

    Directory of Open Access Journals (Sweden)

    Zaikun Xu

    2017-06-01

    Full Text Available HIV-associated neurocognitive disorders (HAND represent a spectrum neurological syndrome that affects up to 25% of patients with HIV/AIDS. Multiple pathogenic mechanisms contribute to the development of HAND symptoms including chronic neuroinflammation and neurodegeneration. Among the factors linked to development of HAND is altered expression of host cell microRNAs (miRNAs in brain. Here, we examined brain miRNA profiles among HIV/AIDS patients with and without HAND. Our analyses revealed differential expression of 17 miRNAs in brain tissue from HAND patients. A subset of the upregulated miRNAs (miR-500a-5p, miR-34c-3p, miR-93-3p and miR-381-3p, are predicted to target peroxisome biogenesis factors (PEX2, PEX7, PEX11B and PEX13. Expression of these miRNAs in transfected cells significantly decreased levels of peroxisomal proteins and concomitantly decreased peroxisome numbers or affected their morphology. The levels of miR-500a-5p, miR-34c-3p, miR-93-3p and miR-381-3p were not only elevated in the brains of HAND patients, but were also upregulated during HIV infection of primary macrophages. Moreover, concomitant loss of peroxisomal proteins was observed in HIV-infected macrophages as well as in brain tissue from HIV-infected patients. HIV-induced loss of peroxisomes was abrogated by blocking the functions of the upregulated miRNAs. Overall, these findings point to previously unrecognized miRNA expression patterns in the brains of HIV patients. Targeting peroxisomes by up-regulating miRNAs that repress peroxisome biogenesis factors may represent a novel mechanism by which HIV-1 subverts innate immune responses and/or causes neurocognitive dysfunction.

  20. Bone mineral density abnormalities in HIV infected patients and HIV ...

    African Journals Online (AJOL)

    Bone mineral density abnormalities in HIV infected patients and HIV ... Comprehensive Care Clinic (CCC) and a HIV negative control group seen at the ... Older patients had lower levels of BMD (i.e. more negative BMD. p-value = 0.032).

  1. The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection.

    LENUS (Irish Health Repository)

    Haedicke, Juliane

    2009-08-18

    Neurons are one of the few cell types in the human body that do not support HIV type-1 (HIV-1) replication. Although the lack of key receptors is a major obstacle to infection, studies suggest that additional functions inhibit virus replication to explain the exquisite resistance of neurons to HIV-1. However, specific neuronal factors that may explain this resistance remain to be discovered. In a screen for antiviral factors using a fibroblast line chemically mutagenized and selected for resistance to retroviral infection, we recently identified induction of rat FEZ1 (fasciculation and elongation protein zeta-1), a brain-specific protein, as the cause of this resistance. When exogenously expressed in nonneuronal cell lines rat FEZ1 blocked nuclear entry of retroviral DNA. Here, we demonstrate that among human brain cells, neurons naturally express high levels of FEZ1 compared to astrocytes or microglia cells and are correspondingly less susceptible to infection with pseudotyped HIV-1 that bypasses receptor-mediated viral entry. Demonstrating that endogenous FEZ1 was functionally important in the resistance of neurons to HIV-1 infection, siRNA-mediated knockdown of endogenous FEZ1 increased the infectivity of neurons while sensitive brain cell types like microglia became more resistant upon FEZ1 overexpression. In addition, FEZ1 expression was not induced in response to IFN treatment. As such, in contrast to other widely expressed, IFN-inducible antiviral factors, FEZ1 appears to represent a unique neuron-specific determinant of cellular susceptibility to infection in a cell type that is naturally resistant to HIV-1.

  2. Reviewing independent access to HIV testing, counselling and treatment for adolescents in HIV-specific laws in sub-Saharan Africa: implications for the HIV response

    Science.gov (United States)

    Eba, Patrick M.; Lim, HyeYoung

    2017-01-01

    Abstract Introduction: AIDS is a leading cause of death among adolescents in sub-Saharan Africa. Yet, legal, policy and social barriers continue to restrict their access to HIV services. In recent years, access to independent HIV testing and treatment for adolescents has gained increased attention. The 2013 WHO Guidance on HIV testing and counselling and care for adolescents living with HIV (WHO Guidance) calls for reviewing legal and regulatory frameworks to facilitate adolescents’ access to comprehensive HIV services. As of 31 March 2017, some 28 countries in sub-Saharan Africa have adopted HIV-specific legislation. But there is limited understanding of the provisions of these laws on access to HIV services for adolescents and their implication on efforts to scale up HIV prevention, testing, treatment and care among this population. Methods: A desk review of 28 HIV-specific laws in sub-Saharan Africa complemented with the review of HIV testing policies in four countries using human rights norms and key public health recommendations from the 2013 WHO Guidance. These recommendations call on countries to (i) lower the age of consent to HIV testing and counselling and allow mature adolescents who have not reached the age of consent to independently access HIV testing, (ii) ensure access to HIV counselling for adolescents, (iii) protect the confidentiality of adolescents living with HIV and (iv) facilitate access to HIV treatment for adolescents living with HIV. Results: Most HIV-specific laws fail to take into account human rights principles and public health recommendations for facilitating adolescents’ access to HIV services. None of the countries with HIV-specific laws has adopted all four recommendations for access to HIV services for adolescents. Discrepancies exist between HIV laws and national policy documents. Inadequate and conflicting provisions in HIV laws are likely to hinder access to HIV testing, counselling and treatment for adolescents

  3. Reviewing independent access to HIV testing, counselling and treatment for adolescents in HIV-specific laws in sub-Saharan Africa: implications for the HIV response.

    Science.gov (United States)

    Eba, Patrick M; Lim, HyeYoung

    2017-08-11

    AIDS is a leading cause of death among adolescents in sub-Saharan Africa. Yet, legal, policy and social barriers continue to restrict their access to HIV services. In recent years, access to independent HIV testing and treatment for adolescents has gained increased attention. The 2013 WHO Guidance on HIV testing and counselling and care for adolescents living with HIV (WHO Guidance) calls for reviewing legal and regulatory frameworks to facilitate adolescents' access to comprehensive HIV services. As of 31 March 2017, some 28 countries in sub-Saharan Africa have adopted HIV-specific legislation. But there is limited understanding of the provisions of these laws on access to HIV services for adolescents and their implication on efforts to scale up HIV prevention, testing, treatment and care among this population. A desk review of 28 HIV-specific laws in sub-Saharan Africa complemented with the review of HIV testing policies in four countries using human rights norms and key public health recommendations from the 2013 WHO Guidance. These recommendations call on countries to (i) lower the age of consent to HIV testing and counselling and allow mature adolescents who have not reached the age of consent to independently access HIV testing, (ii) ensure access to HIV counselling for adolescents, (iii) protect the confidentiality of adolescents living with HIV and (iv) facilitate access to HIV treatment for adolescents living with HIV. Most HIV-specific laws fail to take into account human rights principles and public health recommendations for facilitating adolescents' access to HIV services. None of the countries with HIV-specific laws has adopted all four recommendations for access to HIV services for adolescents. Discrepancies exist between HIV laws and national policy documents. Inadequate and conflicting provisions in HIV laws are likely to hinder access to HIV testing, counselling and treatment for adolescents. Efforts to end legal barriers to access to HIV services

  4. Macro-level implicit HIV prejudice and the health of community residents with HIV.

    Science.gov (United States)

    Miller, Carol T; Varni, Susan E; Solomon, Sondra E; DeSarno, Michael J; Bunn, Janice Y

    2016-08-01

    This study examined how community levels of implicit HIV prejudice are associated with the psychological and physical well-being of people with HIV living in those same communities. It also examined whether community motivation to control prejudice and/or explicit HIV prejudice moderates the relationship of implicit prejudice and well-being. Participants were 206 people with HIV living in 42 different communities in New England who completed measures that assessed psychological distress, thriving, and physical well-being. Telephone surveys of 347 residents of these same communities (selected via random digit dialing) were used to assess community explicit HIV prejudice and motivation to control HIV prejudice. These community residents then completed an online measure of implicit prejudice toward people with HIV, the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998). Multilevel analyses showed that higher community implicit HIV prejudice was associated with greater psychological distress among residents with HIV living in that community. The physical well-being of participants with HIV was negatively related to community implicit HIV prejudice in communities in which residents were unmotivated to control HIV prejudice or had high levels of explicit HIV prejudice. These findings indicate that implicit prejudice of residents of real-world communities may create an environment that may impair the well-being of stigmatized people. Implicit prejudice can therefore be considered an element of macro-level or structural stigma. The discussion considered the possible role of implicit HIV prejudice on a community's social capital as a pathway by which it compromises the well-being of residents with HIV. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Envisioning Women-Centered HIV Care: Perspectives from Women Living with HIV in Canada.

    Science.gov (United States)

    O'Brien, Nadia; Greene, Saara; Carter, Allison; Lewis, Johanna; Nicholson, Valerie; Kwaramba, Gladys; Ménard, Brigitte; Kaufman, Elaina; Ennabil, Nourane; Andersson, Neil; Loutfy, Mona; de Pokomandy, Alexandra; Kaida, Angela

    Women comprise nearly one-quarter of people living with human immunodeficiency virus (HIV) in Canada. Compared with men, women living with HIV experience inequities in HIV care and health outcomes, prompting a need for gendered and tailored approaches to HIV care. Peer and academic researchers from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study conducted focus groups to understand women's experience of seeking care, with the purpose of identifying key characteristics that define a women-centered approach to HIV care. Eleven focus groups were conducted with 77 women living with HIV across Quebec, Ontario, and British Columbia, Canada. Women envisioned three central characteristics of women-centered HIV care, including i) coordinated and integrated services that address both HIV and women's health care priorities, and protect against exclusion from care due to HIV-related stigma, ii) care that recognizes and responds to structural barriers that limit women's access to care, such as violence, poverty, motherhood, HIV-related stigma, and challenges to safe disclosure, and iii) care that fosters peer support and peer leadership in its design and delivery to honor the diversity of women's experiences, overcome women's isolation, and prioritize women's ownership over the decisions that affect their lives. Despite advances in HIV treatment and care, the current care landscape is inadequate to meet women's comprehensive care needs. A women-centered approach to HIV care, as envisioned by women living with HIV, is central to guiding policy and practice to improve care and outcomes for women living with HIV in Canada. Copyright © 2017 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  6. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes....

  7. Evaluating Safer Conception Options for HIV-Serodiscordant Couples (HIV-Infected Female/HIV-Uninfected Male: A Closer Look at Vaginal Insemination

    Directory of Open Access Journals (Sweden)

    Okeoma Mmeje

    2012-01-01

    Full Text Available HIV serodiscordant couples represent at least half of all HIV-affected couples worldwide. Many of these couples have childbearing desires. Safer methods of conception may allow for pregnancy while minimizing the risk of sexual transmission of HIV. In serodiscordant partnerships with an HIV-infected female and HIV-uninfected male, vaginal insemination of a partner's semen during the fertile period coupled with 100% condom use may be the safest method of conception.

  8. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A

    2013-01-01

    HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework o...... of the International epidemiological Databases to Evaluate AIDS (IeDEA)....

  9. Osteopenia and osteoporosis in people living with HIV: multiprofessional approach.

    Science.gov (United States)

    Lima, Ana Lucia Lei Munhoz; de Oliveira, Priscila Rosalba D; Plapler, Perola Grimberg; Marcolino, Flora Maria D Andrea; de Souza Meirelles, Eduardo; Sugawara, André; Gobbi, Riccardo Gomes; Dos Santos, Alexandre Leme Godoy; Camanho, Gilberto Luis

    2011-01-01

    Increasing bone mineralization abnormalities observed among people living with HIV (PLWHIV) result from various factors relating to the host, the virus, and the antiretrovirals used. Today, HIV infection is considered to be a risk factor for bone mineralization disorders. The test most recommended for diagnosing osteoporosis is measurement of bone mineral density by means of dual energy X-ray absorptiometry at two sites. Osteoporosis treatment has the aims of bone mass improvement and fracture control. A combination of calcium and vitamin D supplementation may reduce the risk of fractures. Antiresorptive drugs act by blocking osteoclastic activity and reducing bone remodeling. On the other hand, bone-forming drugs stimulate osteoblastogenesis, thereby stimulating the formation of bone matrix. Mixed-action medications are those that are capable of both stimulating bone formation and inhibiting reabsorption. Antiresorptive drugs form the group of medications with the greatest quantity of scientific evidence confirming their efficacy in osteoporosis treatment. Physical activity is a health promotion strategy for the general population, but only preliminary data on its real value and benefit among PLWHIV are available, especially in relation to osteoporosis.

  10. Epidural block

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000484.htm Epidural block - pregnancy To use the sharing features on this page, please enable JavaScript. An epidural block is a numbing medicine given by injection (shot) ...

  11. Selective translational repression of HIV-1 RNA by Sam68DeltaC occurs by altering PABP1 binding to unspliced viral RNA

    Directory of Open Access Journals (Sweden)

    Soros Vanessa

    2008-10-01

    Full Text Available Abstract HIV-1 structural proteins are translated from incompletely spliced 9 kb and 4 kb mRNAs, which are transported to the cytoplasm by Crm1. It has been assumed that once in the cytoplasm, translation of incompletely spliced HIV-1 mRNAs occurs in the same manner as host mRNAs. Previous analyses have demonstrated that Sam68 and a mutant thereof, Sam68ΔC, have dramatic effects on HIV gene expression, strongly enhancing and inhibiting viral structural protein synthesis, respectively. While investigating the inhibition of incompletely spliced HIV-1 mRNAs by Sam68ΔC, we determined that the effect was independent of the perinuclear bundling of the viral RNA. Inhibition was dependent upon the nuclear export pathway used, as translation of viral RNA exported via the Tap/CTE export pathway was not blocked by Sam68ΔC. We demonstrate that inhibition of HIV expression by Sam68ΔC is correlated with a loss of PABP1 binding with no attendant change in polyadenosine tail length of the affected RNAs. The capacity of Sam68ΔC to selectively inhibit translation of HIV-1 RNAs exported by Crm1 suggests that it is able to recognize unique characteristics of these viral RNPs, a property that could lead to new therapeutic approaches to controlling HIV-1 replication.

  12. Global HIV/AIDS Epidemic

    Science.gov (United States)

    ... Policy The Global HIV/AIDS Epidemic The Global HIV/AIDS Epidemic Published: Nov 29, 2017 Facebook Twitter ... 2001-FY 2018 Request The Global Response to HIV/AIDS International efforts to combat HIV began in ...

  13. HIV/AIDS in Women

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV often ...

  14. HIV Treatment: The Basics

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Treatment: The Basics Last Reviewed: March 22, 2018 ...

  15. Colorectal mucus binds DC-SIGN and inhibits HIV-1 trans-infection of CD4+ T-lymphocytes.

    Directory of Open Access Journals (Sweden)

    Martijn J Stax

    Full Text Available Bodily secretions, including breast milk and semen, contain factors that modulate HIV-1 infection. Since anal intercourse caries one of the highest risks for HIV-1 transmission, our aim was to determine whether colorectal mucus (CM also contains factors interfering with HIV-1 infection and replication. CM from a number of individuals was collected and tested for the capacity to bind DC-SIGN and inhibit HIV-1 cis- or trans-infection of CD4+ T-lymphocytes. To this end, a DC-SIGN binding ELISA, a gp140 trimer competition ELISA and HIV-1 capture/ transfer assays were utilized. Subsequently we aimed to identify the DC-SIGN binding component through biochemical characterization and mass spectrometry analysis. CM was shown to bind DC-SIGN and competes with HIV-1 gp140 trimer for binding. Pre-incubation of Raji-DC-SIGN cells or immature dendritic cells (iDCs with CM potently inhibits DC-SIGN mediated trans-infection of CD4+ T-lymphocytes with CCR5 and CXCR4 using HIV-1 strains, while no effect on direct infection is observed. Preliminary biochemical characterization demonstrates that the component seems to be large (>100kDa, heat and proteinase K resistant, binds in a α1-3 mannose independent manner and is highly variant between individuals. Immunoprecipitation using DC-SIGN-Fc coated agarose beads followed by mass spectrometry indicated lactoferrin (fragments and its receptor (intelectin-1 as candidates. Using ELISA we showed that lactoferrin levels within CM correlate with DC-SIGN binding capacity. In conclusion, CM can bind the C-type lectin DC-SIGN and block HIV-1 trans-infection of both CCR5 and CXCR4 using HIV-1 strains. Furthermore, our data indicate that lactoferrin is a DC-SIGN binding component of CM. These results indicate that CM has the potential to interfere with pathogen transmission and modulate immune responses at the colorectal mucosa.

  16. Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development.

    Directory of Open Access Journals (Sweden)

    Xudong Lin

    Full Text Available BACKGROUND: Approximately 80% of all new HIV-1 infections are acquired through sexual contact. Currently, there is no clinically approved microbicide, indicating a clear and urgent therapeutic need. We recently reported that palmitic acid (PA is a novel and specific inhibitor of HIV-1 fusion and entry. Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo model of human vagina, and determine its effect on Lactobacillus (L species of probiotic vaginal flora. PRINCIPAL FINDINGS: Our results show that treatment with 100-200 µM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this treatment was not toxic to the tissue or to L. crispatus and jensenii species of vaginal flora. In vitro, in a cell free system that is independent of in vivo cell associated CD4 receptor; we determined inhibition constant (Ki to be ∼2.53 µM. SIGNIFICANCE: These results demonstrate utility of PA as a model molecule for further preclinical development of a safe and potent HIV-1 entry microbicide inhibitor.

  17. Parenting and HIV.

    Science.gov (United States)

    Rochat, Tamsen; Netsi, Elena; Redinger, Stephanie; Stein, Alan

    2017-06-01

    With the widespread use of antiretroviral therapy and successful prevention of mother-to-child transmission the development of HIV-negative children with HIV-positive parents has become an important focus. There is considerable evidence that children's developmental risk is heightened because a parental HIV-diagnosis is associated with a range of potential problems such as depression, stigma and financial difficulties. Up to a third of children in sub-Saharan Africa (SSA) are cared for by an HIV-positive parent or caregiver. We review the mechanisms by which HIV affects parenting including its negative effects on parental responsiveness in the early years of parenting and parental avoidant coping styles and parenting deficits in the later years. We describe low-cost parenting interventions suited for low resourced HIV endemic settings. Copyright © 2017. Published by Elsevier Ltd.

  18. HIV Care in the Swedish-Danish HIV Cohort 1995-2010

    DEFF Research Database (Denmark)

    Helleberg, Marie; Häggblom, Amanda; Sönnerborg, Anders

    2013-01-01

    Successful treatment reduces morbidity, mortality and transmission of HIV. We evaluated trends in the treatment status of HIV infected individuals enrolled in care in Sweden and Denmark during the years 1995-2010. Our aim was to assess the proportion of HIV-infected individuals who received...

  19. Nurturing the Continuum of HIV Testing, Treatment and Prevention Matrix Cascade in Reducing HIV Transmission.

    Science.gov (United States)

    Yah, Clarence S

    2017-11-01

    Despite the shift in antiretroviral therapy (ARVs) eligibility cascade from CD4 ≤ 200 to CD4 ≤ 350 to CD4 ≤ 500 mm 3 , HIV related morbidity and mortality continue to escalate annually, as do HIV infections. The new paradigm of treatment for all HIV positives individual irrespective of CD4 count may significantly reduce HIV and related illnesses. The author assumes that all HIV infected partners should be eligible for HIV treatment and care, irrespective of CD4 count. A second assumption is that high risk HIV negative partners have free access to continuum of HIV pre-exposure prophylaxis (PrEP), post exposure prophylaxis (PEP) and other prevention packages. A literature review search was used to extract evidence-based ARVs-HIV treatment and prevention interventions among HIV positives and high risk partners respectively. Only articles published in English and indexed in journal nuclei were used for the study. The information was used to nurture understanding of HIV treatment and prevention approaches as well as HIV incidence multiplier effect among HIV serodiscordant partners. The imputed HIV incident reference was assumed at 1.2 per 100 person-years (2). This was based on the imputation that retention in care, adherence and other predetermined factors are functions of an effective health care delivery system. The model showed a reduced HIV transmission from 1.2 per 100 person-years to 1.032 per 100 person-years in 6 months. The average threshold period of HIV suppressed partners on ARVs to an undetectable level. The combined multiplier protective-effect probability of transmitting HIV from HIV positive partners on ARVs-suppressed viremic load to HIV negative partners on PrEP/PEP-prevention was detected at 86. The model showed a significant reduction in HIV incidence. Placing serodiscordant sexual partners in HIV treatment and prevention plays a significant role in reducing and controlling HIV infection. Therefore, the policy of enrolling all HIV positives

  20. Risk Factors for HIV Transmission and Barriers to HIV Disclosure: Metropolitan Atlanta Youth Perspectives

    OpenAIRE

    Camacho-Gonzalez, Andres F.; Wallins, Amy; Toledo, Lauren; Murray, Ashley; Gaul, Zaneta; Sutton, Madeline Y.; Gillespie, Scott; Leong, Traci; Graves, Chanda; Chakraborty, Rana

    2016-01-01

    Youth carry the highest incidence of HIV infection in the United States. Understanding adolescent and young adult (AYA) perspectives on HIV transmission risk is important for targeted HIV prevention. We conducted a mixed methods study with HIV-infected and uninfected youth, ages 18–24 years, from Atlanta, GA. We provided self-administered surveys to HIV-infected and HIV-uninfected AYAs to identify risk factors for HIV acquisition. By means of computer-assisted thematic analyses, we examined t...

  1. Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV- adults.

    Science.gov (United States)

    Thames, April D; Kuhn, Taylor P; Williamson, Timothy J; Jones, Jacob D; Mahmood, Zanjbeel; Hammond, Andrea

    2017-01-01

    The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals. Participants (HIV+, n=48; HIV-, n=29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.,brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV- MJ users. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections.

    Science.gov (United States)

    Abdi, Mohammad; Rahbari, Rizgar; Khatooni, Zahed; Naseri, Nima; Najafi, Adel; Khodadadi, Iraj

    2016-05-01

    CD4(+) cell count, the common HIV infection screening test, is costly and unable to differentiate HIV monoinfection from its concurrent infection with hepatitis B or C virus. We aimed to ascertain diagnostic value of serum adenosine deaminase (ADA) activity as a useful tool to differentiate HIV mono- and co-infection. Blood samples were collected from 30 HIV-HBV and 30 HIV-HCV coinfected patients, 33 HIV positive subjects, and 72 controls. CD4(+) cell count, serum total ADA (tADA), and ADA1, and ADA2 isoenzyme activities were determined and their sensitivity and specificity were computed. tADA and ADA2 activities were significantly higher and CD4(+) counts were markedly lower in all patients compared with controls. Strong inverse agreements between CD4(+) cell counts and both tADA and ADA2 activities were observed. Serum tADA and ADA1 activities showed the highest specificity and the highest sensitivity, respectively, for differentiating HIV monoinfection from HIV-HBV and HIV-HCV coinfections. We showed strong agreement and correlation between CD4(+) cell count and ADA enzyme activity. Based on high ADA sensitivity and specificity, it is concluded that determination of ADA activity might be a novel diagnostic tool to distinguish of HIV monoinfection from its coinfection with HBV or HCV. © 2015 Wiley Periodicals, Inc.

  3. Detection of HIV-1 and Human Proteins in Urinary Extracellular Vesicles from HIV+ Patients

    Directory of Open Access Journals (Sweden)

    Samuel I. Anyanwu

    2018-01-01

    Full Text Available Background. Extracellular vesicles (EVs are membrane bound, secreted by cells, and detected in bodily fluids, including urine, and contain proteins, RNA, and DNA. Our goal was to identify HIV and human proteins (HPs in urinary EVs from HIV+ patients and compare them to HIV− samples. Methods. Urine samples were collected from HIV+ (n=35 and HIV− (n=12 individuals. EVs were isolated by ultrafiltration and characterized using transmission electron microscopy, tandem mass spectrometry (LC/MS/MS, and nanoparticle tracking analysis (NTA. Western blots confirmed the presence of HIV proteins. Gene ontology (GO analysis was performed using FunRich and HIV Human Interaction database (HHID. Results. EVs from urine were 30–400 nm in size. More EVs were in HIV+ patients, P<0.05, by NTA. HIV+ samples had 14,475 HPs using LC/MS/MS, while only 111 were in HIV−. HPs in the EVs were of exosomal origin. LC/MS/MS showed all HIV+ samples contained at least one HIV protein. GO analysis showed differences in proteins between HIV+ and HIV− samples and more than 50% of the published HPs in the HHID interacted with EV HIV proteins. Conclusion. Differences in the proteomic profile of EVs from HIV+ versus HIV− samples were found. HIV and HPs in EVs could be used to detect infection and/or diagnose HIV disease syndromes.

  4. Comparing HIV prevalence estimates from prevention of mother-to-child HIV transmission programme and the antenatal HIV surveillance in Addis Ababa

    Directory of Open Access Journals (Sweden)

    Mirkuzie Alemnesh H

    2012-12-01

    Full Text Available Abstract Background In the absence of reliable data, antenatal HIV surveillance has been used to monitor the HIV epidemic since the late 1980s. Currently, routine data from Prevention of Mother-to-child HIV transmission (PMTCT programmes are increasingly available. Evaluating whether the PMTCT programme reports provide comparable HIV prevalence estimates with the antenatal surveillance reports is important. In this study, we compared HIV prevalence estimates from routine PMTCT programme and antenatal surveillance in Addis Ababa with the aim to come up with evidence based recommendation. Methods Summary data were collected from PMTCT programmes and antenatal surveillance reports within the catchment of Addis Ababa. The PMTCT programme data were obtained from routine monthly reports from 2004 to 2009 and from published antenatal HIV surveillance reports from 2003 to 2009. Data were analysed using descriptive statistics. Results In Addis Ababa, PMTCT sites had increased from six in 2004 to 54 in 2009. The site expansion was accompanied by an increased number of women testing. There were marked increases in the rate of HIV testing following the introduction of routine opt-out HIV testing approach. Paralleling these increases, the HIV prevalence showed a steady decline from 10.0% in 2004 to 4.5% in 2009. There were five antenatal surveillance sites from 2003 to 2007 in Addis Ababa and they increased to seven by 2009. Four rounds of surveillance data from five sites showed a declining trend in HIV prevalence over the years. The overall antenatal surveillance data also showed that the HIV prevalence among antenatal attendees had declined from 12.4% in 2003 to 5.5% in 2009. The HIV prevalence estimates from PMTCT programme were 6.2% and 4.5% and from antenatal surveillance 6.1 and 5.5% in 2008 and 2009 respectively. Conclusions There were consistent HIV prevalence estimates from PMTCT programme and from antenatal surveillance reports. Both data sources

  5. Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes

    International Nuclear Information System (INIS)

    Ketas, Thomas J.; Schader, Susan M.; Zurita, Juan; Teo, Esther; Polonis, Victoria; Lu Min; Klasse, Per Johan; Moore, John P.

    2007-01-01

    Inhibitors of viral entry are under consideration as topical microbicides to prevent HIV-1 sexual transmission. Small molecules targeting HIV-1 gp120 (BMS-378806) or CCR5 (CMPD167), and a peptide fusion inhibitor (C52L), each blocks vaginal infection of macaques by a SHIV. A microbicide, however, must be active against multiple HIV-1 variants. We therefore tested BMS-C (a BMS-378806 derivative), CMPD167, C52L and the CXCR4 ligand AMD3465, alone and in combination, against 25 primary R5, 12 X4 and 7 R5X4 isolates from subtypes A-G. At high concentrations (0.1-1 μM), the replication of most R5 isolates in human donor lymphocytes was inhibited by > 90%. At lower concentrations, double and triple combinations were more effective than individual inhibitors. Similar results were obtained with X4 viruses when AMD3465 was substituted for CMPD167. The R5X4 viruses were inhibited by combining AMD3465 with CMPD167, or by the coreceptor-independent compounds. Thus, combining entry inhibitors may improve microbicide effectiveness

  6. Predictability of blocking

    International Nuclear Information System (INIS)

    Tosi, E.; Ruti, P.; Tibaldi, S.; D'Andrea, F.

    1994-01-01

    Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

  7. Determination of HIV Status in African Adults With Discordant HIV Rapid Tests.

    Science.gov (United States)

    Fogel, Jessica M; Piwowar-Manning, Estelle; Donohue, Kelsey; Cummings, Vanessa; Marzinke, Mark A; Clarke, William; Breaud, Autumn; Fiamma, Agnès; Donnell, Deborah; Kulich, Michal; Mbwambo, Jessie K K; Richter, Linda; Gray, Glenda; Sweat, Michael; Coates, Thomas J; Eshleman, Susan H

    2015-08-01

    In resource-limited settings, HIV infection is often diagnosed using 2 rapid tests. If the results are discordant, a third tie-breaker test is often used to determine HIV status. This study characterized samples with discordant rapid tests and compared different testing strategies for determining HIV status in these cases. Samples were previously collected from 173 African adults in a population-based survey who had discordant rapid test results. Samples were classified as HIV positive or HIV negative using a rigorous testing algorithm that included two fourth-generation tests, a discriminatory test, and 2 HIV RNA tests. Tie-breaker tests were evaluated, including rapid tests (1 performed in-country), a third-generation enzyme immunoassay, and two fourth-generation tests. Selected samples were further characterized using additional assays. Twenty-nine samples (16.8%) were classified as HIV positive and 24 of those samples (82.8%) had undetectable HIV RNA. Antiretroviral drugs were detected in 1 sample. Sensitivity was 8.3%-43% for the rapid tests; 24.1% for the third-generation enzyme immunoassay; 95.8% and 96.6% for the fourth-generation tests. Specificity was lower for the fourth-generation tests than the other tests. Accuracy ranged from 79.5% to 91.3%. In this population-based survey, most HIV-infected adults with discordant rapid tests were virally suppressed without antiretroviral drugs. Use of individual assays as tie-breaker tests was not a reliable method for determining HIV status in these individuals. More extensive testing algorithms that use a fourth-generation screening test with a discriminatory test and HIV RNA test are preferable for determining HIV status in these cases.

  8. HIV transmission risk among HIV seroconcordant and serodiscordant couples: dyadic processes of partner selection.

    Science.gov (United States)

    Eaton, Lisa A; West, Tessa V; Kenny, David A; Kalichman, Seth C

    2009-04-01

    Selecting sex partners of the same HIV status or serosorting is a sexual risk reduction strategy used by many men who have sex with men. However, the effectiveness of serosorting for protection against HIV is potentially limited. We sought to examine how men perceive the protective benefits of factors related to serosorting including beliefs about engaging in serosorting, sexual communication, and perceptions of risk for HIV. Participants were 94 HIV negative seroconcordant (same HIV status) couples, 20 HIV serodiscordant (discrepant HIV status) couples, and 13 HIV positive seroconcordant (same HIV status) couples recruited from a large gay pride festival in the southeastern US. To account for nonindependence found in the couple-level data, we used multilevel modeling which includes dyad in the analysis. Findings demonstrated that participants in seroconcordant relationships were more likely to believe that serosorting reduces concerns for condom use. HIV negative participants in seroconcordant relationships viewed themselves at relatively low risk for HIV transmission even though monogamy within relationships and HIV testing were infrequent. Dyadic analyses demonstrated that partners have a substantial effect on an individual's beliefs and number of unprotected sex partners. We conclude that relationship partners are an important source of influence and, thus, intervening with partners is necessary to reduce HIV transmission risks.

  9. Recruitment of a SAP18-HDAC1 complex into HIV-1 virions and its requirement for viral replication.

    Directory of Open Access Journals (Sweden)

    Masha Sorin

    2009-06-01

    Full Text Available HIV-1 integrase (IN is a virally encoded protein required for integration of viral cDNA into host chromosomes. INI1/hSNF5 is a component of the SWI/SNF complex that interacts with HIV-1 IN, is selectively incorporated into HIV-1 (but not other retroviral virions, and modulates multiple steps, including particle production and infectivity. To gain further insight into the role of INI1 in HIV-1 replication, we screened for INI1-interacting proteins using the yeast two-hybrid system. We found that SAP18 (Sin3a associated protein 18 kD, a component of the Sin3a-HDAC1 complex, directly binds to INI1 in yeast, in vitro and in vivo. Interestingly, we found that IN also binds to SAP18 in vitro and in vivo. SAP18 and components of a Sin3A-HDAC1 complex were specifically incorporated into HIV-1 (but not SIV and HTLV-1 virions in an HIV-1 IN-dependent manner. Using a fluorescence-based assay, we found that HIV-1 (but not SIV virion preparations harbour significant deacetylase activity, indicating the specific recruitment of catalytically active HDAC into the virions. To determine the requirement of virion-associated HDAC1 to HIV-1 replication, an inactive, transdominant negative mutant of HDAC1 (HDAC1(H141A was utilized. Incorporation of HDAC1(H141A decreased the virion-associated histone deacetylase activity. Furthermore, incorporation of HDAC1(H141A decreased the infectivity of HIV-1 (but not SIV virions. The block in infectivity due to virion-associated HDAC1(H141A occurred specifically at the early reverse transcription stage, while entry of the virions was unaffected. RNA-interference mediated knock-down of HDAC1 in producer cells resulted in decreased virion-associated HDAC1 activity and a reduction in infectivity of these virions. These studies indicate that HIV-1 IN and INI1/hSNF5 bind SAP18 and selectively recruit components of Sin3a-HDAC1 complex into HIV-1 virions. Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post

  10. HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

    Science.gov (United States)

    Lu, Xinli; Kang, Xianjiang; Liu, Yongjian; Cui, Ze; Guo, Wei; Zhao, Cuiying; Li, Yan; Chen, Suliang; Li, Jingyun; Zhang, Yuqi; Zhao, Hongru

    2017-01-01

    New human immunodeficiency virus type 1 (HIV-1) diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF)01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%), and unique recombinant forms URFs (4.9%). Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx), unknown before in Hebei, were first found among men who have sex with men (MSM). All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

  11. HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

    Directory of Open Access Journals (Sweden)

    Xinli Lu

    Full Text Available New human immunodeficiency virus type 1 (HIV-1 diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF01_AE (53.4%, CRF07_BC (23.4%, subtype B (15.9%, and unique recombinant forms URFs (4.9%. Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx, unknown before in Hebei, were first found among men who have sex with men (MSM. All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%, CRF01_AE/B (23.3%, B/C (16.7%, CRF01_AE/C (13.3%, CRF01_AE/B/A2 (3.3% and CRF01_AE/BC/A2 (3.3%, plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

  12. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  13. Asymptomatic HIV infection

    Science.gov (United States)

    ... of HIV/AIDS during which there are no symptoms of HIV infection. During this phase, the immune system in someone with HIV slowly weakens, but the person has no symptoms. How long this phase lasts depends on how ...

  14. Neuro-HIV: Nervous System Manifestations of HIV Infection- A Review

    African Journals Online (AJOL)

    Neuro-HIV: Nervous System Manifestations of HIV Infection- A Review. ... Open Access DOWNLOAD FULL TEXT Subscription or Fee Access ... The early detection of neurological disease due to HIV infection is of paramount importance to the clinician as there are implications not just for management but also for prognosis.

  15. HIV-positive and HIV-negative consumers accept an instant soy ...

    African Journals Online (AJOL)

    HIV-positive and HIV-negative consumers accept an instant soy maize porridge. ... Health SA Gesondheid ... The objective of this study was to assess consumer acceptability, preference and consumption intent of an instant soy ... as a food supplement for HIV subjects in a subsequent nutrition intervention trial, to improve

  16. Travelling with HIV

    DEFF Research Database (Denmark)

    Nielsen, Ulla S; Jensen-Fangel, Søren; Pedersen, Gitte

    2014-01-01

    BACKGROUND: We aimed to describe travel patterns, extent of professional pre-travel advice and health problems encountered during travel among HIV-infected individuals. METHODS: During a six-month period a questionnaire was handed out to 2821 adult HIV-infected individuals attending any...... of the eight Danish medical HIV care centers. RESULTS: A total of 763 individuals responded. During the previous two years 49% had travelled outside Europe; 18% had travelled less and 30% were more cautious when choosing travel destination than before the HIV diagnosis. Pre-travel advice was sought by only 38......%, and travel insurance was taken out by 86%. However, 29%/74% did not inform the advisor/the insurance company about their HIV status. Nearly all patients on highly active antiretroviral therapy (HAART) were adherent, but 58% worried about carrying HIV-medicine and 19% tried to hide it. Only 19% experienced...

  17. HIV and Cardiovascular Disease

    Science.gov (United States)

    ... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...

  18. Discordant HIV Test Results: Implications on Perinatal and Haemotransfusion Screening for HIV Infection, Cape Coast, Ghana.

    Science.gov (United States)

    Tetteh, Ato Kwamena; Agyarko, Edward

    2017-01-01

    Screening results of 488 pregnant women aged 15-44 years whose blood samples had been tested on-site, using First Response® HIV 1/2, and confirmed with INNO-LIA™ HIV I/II Score were used. Of this total, 178 were reactive (HIV I, 154; HIV II, 2; and HIV I and HIV II, 22). Of the 154 HIV I-reactive samples, 104 were confirmed to be HIV I-positive and 2 were confirmed to be HIV II-positive, while 48 were confirmed to be negative [false positive rate = 17.44% (13.56-21.32)]. The two HIV II samples submitted were confirmed to be negative with the confirmatory test. For the 22 HIV I and HIV II samples, 7 were confirmed to be HIV I-positive and 1 was confirmed to be HIV I- and HIV II-positive, while 14 were confirmed to be negative. Of the 310 nonreactive samples, 6 were confirmed to be HIV I-positive and 1 was confirmed to be HIV II-positive [false negative rate = 5.79% (1.63-8.38)], while 303 were negative. False negative outcomes will remain unconfirmed, with no management options for the client. False negative rate of 5.79% requires attention, as its resultant implications on control of HIV/AIDS could be dire.

  19. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

  20. Natural controlled HIV infection: Preserved HIV-specific immunity despite undetectable replication competent virus

    International Nuclear Information System (INIS)

    Kloosterboer, Nico; Groeneveld, Paul H.P.; Jansen, Christine A.; Vorst, Teun J.K. van der; Koning, Fransje; Winkel, Carel N.; Duits, Ashley J.; Miedema, Frank; Baarle, Debbie van; Rij, Ronald P. van; Brinkman, Kees; Schuitemaker, Hanneke

    2005-01-01

    Long-term non-progressive HIV infection, characterized by low but detectable viral load and stable CD4 counts in the absence of antiviral therapy, is observed in about 5% of HIV-infected patients. Here we identified four therapy naive individuals who are strongly seropositive for HIV-1 but who lack evidence of detectable HIV p24 antigen, plasma RNA, and proviral DNA in routine diagnostic testing. With an ultrasensitive PCR, we established that frequencies of pol proviral DNA sequences were as low as 0.2-0.5 copies/10 6 PBMC. HIV could not be isolated using up to 30 x 10 6 patient PBMC. One individual was heterozygous for CCR5 Δ32, but CCR5 expression on CD4 + T cells was normal to high in all four individuals. In vitro R5 and X4 HIV-1 susceptibility of CD8-depleted PBMC of all study subjects was significantly lower than the susceptibility of CD8-depleted PBMC of healthy blood donors. All individuals expressed protective HLA-B*58s alleles and showed evidence of HIV-specific cellular immunity either by staining with HLA-B*57 tetramers folded with an HIV RT or gag peptide or after stimulation with HIV-1 p24 gag, RT, or nef peptides in ELIspot analysis. HIV-specific CD4 + T helper cells were demonstrated by proliferation of CD4 + T cells and intracellular staining for IL-2 and IFNγ after stimulation with an HIV-gag peptide pool. Sera of all individuals showed antibody-mediated neutralization of both R5 and X4 HIV-1 variants. These data implicate that very low-level antigen exposure is sufficient for sustained HIV-specific immunity and suggest the possibility of a multi-factorial control of HIV infection

  1. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  2. Dolutegravir as maintenance monotherapy for HIV (DOMONO): a phase 2, randomised non-inferiority trial.

    Science.gov (United States)

    Wijting, Ingeborg; Rokx, Casper; Boucher, Charles; van Kampen, Jeroen; Pas, Suzan; de Vries-Sluijs, Theodora; Schurink, Carolina; Bax, Hannelore; Derksen, Maarten; Andrinopoulou, Eleni-Rosalina; van der Ende, Marchina; van Gorp, Eric; Nouwen, Jan; Verbon, Annelies; Bierman, Wouter; Rijnders, Bart

    2017-12-01

    The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART. We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands. Eligible patients (aged ≥18 years) were on combination ART, had been virologically suppressed (HIV RNA <50 copies per mL) for at least 6 months, and had CD4 nadirs of 200 cells per μL or higher, HIV RNA zeniths of 100 000 copies per mL or less, and no history of virological failure. Patients were randomly assigned (1:1), via a web-based block randomisation method (variable block sizes of 4 and 6), to switch to dolutegravir monotherapy (50 mg once a day) either immediately or after a delay of 24 weeks of continued combination ART. Randomisation was stratified by HIV RNA zenith (<50 000 copies per mL vs 50 000-99 999 copies per mL). Investigators and patients were not masked to group allocation. The primary endpoint was the proportion of patients with plasma HIV RNA viral loads of less than 200 copies per mL at week 24, with a non-inferiority margin of 12%. We did analyses in the on-treatment and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, NCT02401828. Between March 10, 2015, and Feb 4, 2016, we randomly assigned 51 patients to the immediate switch group and 53 patients to the delayed switch group. One patient who received immediate monotherapy discontinued treatment at week 12 because of disturbed sleep. At week 24, dolutegravir monotherapy was non-inferior to combination ART, with plasma HIV RNA loads of 200 copies per mL or higher observed in 2% (1/50) of patients in the immediate switch group and in no patients in the delayed switch group (difference 2%, 95% CI

  3. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  4. HIV Antibody Test

    Science.gov (United States)

    ... 65 in the case of the USPSTF) and pregnant women be screened for HIV at least once. The CDC and American College ... to make sure she is not infected with HIV before getting pregnant may opt to get tested (see Pregnancy: HIV .) ...

  5. Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells.

    Science.gov (United States)

    Payne, Emily H; Ramalingam, Dhivya; Fox, Donald T; Klotman, Mary E

    2018-01-15

    Prior studies have found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy have remained unclear. Here we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). We found that as in many cell types, Vpr first initiates G 2 cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy. Specifically, we found that a fraction of G 2 -arrested RTECs reenter the cell cycle. Following this cell cycle reentry, two distinct outcomes occur. Cells that enter complete mitosis undergo mitotic cell death due to extra centrosomes and aberrant division. Conversely, cells that abort mitosis undergo endoreplication to become polyploid. We further show that multiple small-molecule inhibitors of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including those that target ATR, ATM, and mTOR, indirectly prevent Vpr-mediated polyploidy by preventing G 2 arrest. In contrast, an inhibitor that targets DNA-dependent protein kinase (DNA-PK) specifically blocks the Vpr-mediated transition from G 2 arrest to polyploidy. These findings outline a temporal, molecularly regulated path to polyploidy in HIV-positive renal cells. IMPORTANCE Current cure-focused efforts in HIV research aim to elucidate the mechanisms of long-term persistence of HIV in compartments. The kidney is recognized as one such compartment, since viral DNA and mRNA persist in the renal tissues of HIV-positive patients. Further, renal disease is a long-term comorbidity in the setting of HIV. Thus, understanding the regulation and impact of HIV infection on renal cell biology will provide important insights into this unique HIV compartment. Our work identifies mechanisms that distinguish

  6. Usefulness of the HIV dementia scale in nigerian patients with HIV ...

    African Journals Online (AJOL)

    Saharan Africa, where statistics on HIV are alarming, is sparse because of lack of validated cognitive tools. This study assessed the usefulness and predictive validity of the HIV Dementia Scale (HDS) as a screening tool in HIV-positive Nigerians.

  7. Physics of HIV

    Science.gov (United States)

    Tristram-Nagle, Stephanie

    2018-05-01

    This review summarizes over a decade of investigations into how membrane-binding proteins from the HIV-1 virus interact with lipid membrane mimics of various HIV and host T-cell membranes. The goal of the work was to characterize at the molecular level both the elastic and structural changes that occur due to HIV protein/membrane interactions, which could lead to new drugs to thwart the HIV virus. The main technique used to study these interactions is diffuse x-ray scattering, which yields the bending modulus, K C, as well as structural parameters such as membrane thickness, area/lipid and position of HIV peptides (parts of HIV proteins) in the membrane. Our methods also yield information about lipid chain order or disorder caused by the peptides. This review focuses on three stages of the HIV-1 life cycle: (1) infection, (2) Tat membrane transport, and (3) budding. In the infection stage, our lab studied three different parts of HIV-1 gp41 (glycoprotein 41 fusion protein): (1) FP23, the N-terminal 23 amino acids that interact non-specifically with the T-cell host membrane to cause fusion of two membranes, and its trimer version, (2) cholesterol recognition amino acid consensus sequence, on the membrane proximal external region near the membrane-spanning domain, and (3) lentiviral lytic peptide 2 on the cytoplasmic C-terminal tail. For Tat transport, we used membrane mimics of the T-cell nuclear membrane as well as simpler models that varied charge and negative curvature. For membrane budding, we varied the myristoylation of the MA31 peptide as well as the negatively charged lipid. These studies show that HIV peptides with different roles in the HIV life cycle affect differently the relevant membrane mimics. In addition, the membrane lipid composition plays an important role in the peptides’ effects.

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. About HIV/AIDS. ( https://www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, ...

  9. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    2011-06-09

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses National HIV Testing Day, an annual observance which raises awareness of the importance of knowing one's HIV status and encourages at-risk individuals to get an HIV test.  Created: 6/9/2011 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 6/9/2011.

  10. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    2012-11-26

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.  Created: 11/26/2012 by Division of HIV/AIDS Prevention.   Date Released: 11/26/2012.

  11. Knowledge of HIV/AIDS and attitudes towards people living with HIV ...

    African Journals Online (AJOL)

    Stigma and discrimination towards people living with HIV have been widely documented, and have extended their impact into the workplace. Stigmatising attitudes towards people living with HIV (PLHIV) in the workplace significantly hinder HIV prevention efforts and indirectly affect national development.

  12. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses National HIV Testing Day, an annual observance which raises awareness of the importance of knowing one's HIV status and encourages at-risk individuals to get an HIV test.

  13. Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China.

    Science.gov (United States)

    Li, Fan; Ma, Liying; Feng, Yi; Hu, Jing; Ni, Na; Ruan, Yuhua; Shao, Yiming

    2017-06-01

    HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines.

  14. Immune defence against HIV-1 infection in HIV-1-exposed seronegative persons.

    Science.gov (United States)

    Schmechel, S C; Russell, N; Hladik, F; Lang, J; Wilson, A; Ha, R; Desbien, A; McElrath, M J

    2001-11-01

    Rare individuals who are repeatedly exposed to HIV-1 through unprotected sexual contact fail to acquire HIV-1 infection. These persons represent a unique study population to evaluate mechanisms by which HIV-1 replication is either prevented or controlled. We followed longitudinally a group of healthy HIV-1 seronegative persons each reporting repeated high-risk sexual activities with their HIV-1-infected partner at enrollment. The volunteers were primarily (90%) male homosexuals, maintaining high risk activities with their known infected partner (45%) or multiple other partners (61%). We evaluated the quantity and specificity of HIV-1-specific T cells in 31 exposed seronegatives (ES) using a IFN-gamma ELISPOT assay to enumerate T cells recognizing epitopes within HIV-1 Env, Gag, Pol and Nef. PBMC from only three of the 31 volunteers demonstrated ex vivo HIV-1-specific IFN-gamma secretion, in contrast to nearly 30% exhibiting cytolytic responses in previous studies. These findings suggest that if T cell responses in ES are induced by HIV-1 exposure, the frequency is at low levels in most of them, and below the level of detection using the ELISPOT assay. Alternative approaches to improve the sensitivity of detection may include use of dendritic cells as antigen-presenting cells in the ex vivo assay and more careful definition of the risk behavior and extent of HIV-1 exposure in conjunction with the evaluation of T cell responses.

  15. Detection block

    International Nuclear Information System (INIS)

    Bezak, A.

    1987-01-01

    A diagram is given of a detection block used for monitoring burnup of nuclear reactor fuel. A shielding block is an important part of the detection block. It stabilizes the fuel assembly in the fixing hole in front of a collimator where a suitable gamma beam is defined for gamma spectrometry determination of fuel burnup. The detector case and a neutron source case are placed on opposite sides of the fixing hole. For neutron measurement for which the water in the tank is used as a moderator, the neutron detector-fuel assembly configuration is selected such that neutrons from spontaneous fission and neutrons induced with the neutron source can both be measured. The patented design of the detection block permits longitudinal travel and rotation of the fuel assembly to any position, and thus more reliable determination of nuclear fuel burnup. (E.S.). 1 fig

  16. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation

    Science.gov (United States)

    Granelli-Piperno, Angela; Golebiowska, Angelika; Trumpfheller, Christine; Siegal, Frederick P.; Steinman, Ralph M.

    2004-05-01

    Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers. If different maturation stimuli are applied to DCs infected with HIV-1, the infected cells selectively fail to mature. When DCs from HIV-1-infected patients are infected and cultured with autologous T cells, IL-10 was produced in 6 of 10 patients. These DC-T cell cocultures could suppress another immune response, the MLR. The regulation was partially IL-10-dependent and correlated in extent with the level of IL-10 produced. Suppressor cells only developed from infected patients, rather than healthy controls, and the DCs had to be exposed to live virus rather than HIV-1 gag peptides or protein. These results indicate that HIV-1-infected DCs have two previously unrecognized means to evade immune responses: maturation can be blocked reducing the efficacy of antigen presentation from infected cells, and T cell-dependent suppression can be induced.

  17. Humanizing HIV/AIDS and its (re)stigmatizing effects: HIV public 'positive' speaking in India.

    Science.gov (United States)

    Finn, Mark; Sarangi, Srikant

    2009-01-01

    Social stigma has been inextricably linked with HIV and AIDS since the epidemic erupted in the early 1980s. The stigma that has built up around HIV and AIDS is generally regarded as having a negative impact on the quality of life of HIV-positive people and on general prevention efforts. Current attempts to combat HIV-related stigma focus on increasing the acceptance of HIV among the stigmatizing public and stigmatized individuals alike. In this, the global HIV-positive community is being increasingly called upon to ;humanize' the virus, not least through public displays of HIV 'positive' health and public ;positive' speaking. This article critically explores the constitutive effects and inherent power relations of HIV Positive Speakers' Bureaus (PSBs) as a platform for such a display. Adopting a post-structuralist discourse analytic approach, we explore accounts of positive-speaking and HIV health from HIV-related non-government organizations in India and in PSB training manuals. In particular, we highlight ways in which positive-speaking in India can be seen to have significant (re)stigmatizing effects by way of ambivalent and hyper-real configurations of HIV 'positive' identity and life.

  18. HIV and chronic kidney disease

    OpenAIRE

    Naicker, Saraladevi; Rahmania, Sadaf; Kopp, Jeffrey B.

    2015-01-01

    Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 – 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune comple...

  19. The impact of HIV clinical pharmacists on HIV treatment outcomes: a systematic review

    Directory of Open Access Journals (Sweden)

    Saberi P

    2012-04-01

    Full Text Available Parya Saberi1, Betty J Dong2, Mallory O Johnson1, Ruth M Greenblatt2, Jennifer M Cocohoba21Department of Medicine, 2Department of Clinical Pharmacy, University of California, San Francisco, CA, USAObjective: Due to the rapid proliferation of human immunodeficiency virus (HIV treatment options, there is a need for health care providers with knowledge of antiretroviral therapy intricacies. In a HIV multidisciplinary care team, the HIV pharmacist is well-equipped to provide this expertise. We conducted a systematic review to assess the impact of HIV pharmacists on HIV clinical outcomes.Methods: We searched six electronic databases from January 1, 1980 to June 1, 2011 and included all quantitative studies that examined pharmacist's roles in the clinical care of HIV-positive adults. Primary outcomes were antiretroviral adherence, viral load, and CD4+ cell count and secondary outcomes included health care utilization parameters, antiretroviral modifications, and other descriptive variables.Results: Thirty-two publications were included. Despite methodological limitation, the involvement of HIV pharmacists was associated with statistically significant adherence improvements and positive impact on viral suppression in the majority of studies.Conclusion: This systematic review provides evidence of the beneficial impact of HIV pharmacists on HIV treatment outcomes and offers suggestions for future research.Keywords: pharmacist, HIV/AIDS, clinical, adherence, impact

  20. EASY-HIT: HIV full-replication technology for broad discovery of multiple classes of HIV inhibitors.

    Science.gov (United States)

    Kremb, Stephan; Helfer, Markus; Heller, Werner; Hoffmann, Dieter; Wolff, Horst; Kleinschmidt, Andrea; Cepok, Sabine; Hemmer, Bernhard; Durner, Jörg; Brack-Werner, Ruth

    2010-12-01

    HIV replication assays are important tools for HIV drug discovery efforts. Here, we present a full HIV replication system (EASY-HIT) for the identification and analysis of HIV inhibitors. This technology is based on adherently growing HIV-susceptible cells, with a stable fluorescent reporter gene activated by HIV Tat and Rev. A fluorescence-based assay was designed that measures HIV infection by two parameters relating to the early and the late phases of HIV replication, respectively. Validation of the assay with a panel of nine reference inhibitors yielded effective inhibitory concentrations consistent with published data and allowed discrimination between inhibitors of early and late phases of HIV replication. Finer resolution of the effects of reference drugs on different steps of HIV replication was achieved in secondary time-of-addition assays. The EASY-HIT assay yielded high Z' scores (>0.9) and signal stabilities, confirming its robustness. Screening of the LOPAC(1280) library identified 10 compounds (0.8%), of which eight were known to inhibit HIV, validating the suitability of this assay for screening applications. Studies evaluating anti-HIV activities of natural products with the EASY-HIT technology led to the identification of three novel inhibitory compounds that apparently act at different steps of HIV-1 replication. Furthermore, we demonstrate successful evaluation of plant extracts for HIV-inhibitory activities, suggesting application of this technology for the surveillance of biological extracts with anti-HIV activities. We conclude that the EASY-HIT technology is a versatile tool for the discovery and characterization of HIV inhibitors.

  1. Generationing, Stealthing, and Gift Giving: The Intentional Transmission of HIV by HIV-Positive Men to their HIV-Negative Sex Partners.

    Science.gov (United States)

    Klein, Hugh

    2014-11-06

    Gift giving is the process by which an HIV-positive person purposely infects an HIV-negative person with HIV, usually with that person's knowledge and consent. Little has been written about this HIV transmission practice. In this paper, two specific types of gift giving - generationing and stealthing - are explained and introduced to the scientific literature. Generationing is a type of gift giving in which one gift giver successfully infects a previously-uninfected man with HIV, and then the two men collaborate in an effort to seroconvert another man, and so forth. Stealthing is another type of gift giving in which an HIV-positive man actively tries to infect an HIV-negative man with HIV, without the latter's knowledge or consent. The present study reports on the prevalence of gift giving (4.6%) in a population of men who use the Internet specifically to identify partners for unprotected sex. The research is based on a national random sample of 332 men who have sex with men, identified from 16 websites. Data were collected via telephone interviews conducted between January 2008 and May 2009. The paper concludes with a discussion of the implications of these findings for HIV prevention and intervention efforts. Most notably, to the extent that generationing, stealthing, and gift giving occur among MSM, they represent a very high risk of HIV transmission. More work needs to be done to understand these behaviors, the factors that underlie them, and to determine how prevalent they are in the bare-backing population of MSM.

  2. Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

    Science.gov (United States)

    deCamp, Allan C; Rolland, Morgane; Edlefsen, Paul T; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A; Fiore-Gartland, Andrew J; Juraska, Michal; Carpp, Lindsay N; Karuna, Shelly T; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z; Gottardo, Raphael; Koup, Richard A; Bailer, Robert; Mascola, John R; Graham, Barney S; Roederer, Mario; O'Connell, Robert J; Michael, Nelson L; Robb, Merlin L; Adams, Elizabeth; D'Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E; Frahm, Nicole; Tomaras, Georgia D; McElrath, M Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E; Hammer, Scott M; Kim, Jerome H; Mullins, James I; Gilbert, Peter B

    2017-01-01

    Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

  3. Food insecurity, depression, and social support in HIV-infected Hispanic individuals.

    Science.gov (United States)

    Kapulsky, Leonid; Tang, Alice M; Forrester, Janet E

    2015-04-01

    Previous research has identified an association between food insecurity and depression in a variety of world regions in both healthy and HIV-infected individuals. We examined this association in 183 HIV-infected Hispanic adults from the greater Boston area. We measured depression with the Burnam depression screen and food insecurity with the Radimer/Cornell Questionnaire. Dietary intake was assessed with an adapted version of the Block Food Frequency Questionnaire. Logistic regression models were created with depression as the outcome variable and food insecurity as the main predictor. In bivariate analyses, food insecurity was significantly associated with depression [odds ratio (OR) 2.5; 95% confidence interval (CI) 1.1, 5.5; p = 0.03]. When we accounted for social support, food insecurity was no longer significant. We found no differences in the quality or quantity of dietary intake between the food insecure and food secure groups. Our findings highlight the importance of social support in the association between food insecurity and depression. Food insecurity may reflect social support more than actual dietary intake in this population.

  4. The HIV/AIDS epidemic in Cuba: description and tentative explanation of its low HIV prevalence

    Directory of Open Access Journals (Sweden)

    Clémençon Stéphan

    2007-11-01

    Full Text Available Abstract Background The Cuban HIV/AIDS epidemic has the lowest prevalence rate of the Caribbean region. The objective of this paper is to give an overview of the HIV/AIDS epidemic in Cuba and to explore the reasons for this low prevalence. Methods Data were obtained from the Cuban HIV/AIDS programme established in 1983. This programme has an extensive adult HIV testing policy, including testing of all pregnant women. HIV and AIDS cases have been recorded since 1986. Persons found to be HIV-positive are interviewed on their sexual behaviour and partners. Tracing and voluntary testing of these partners are organised. Epidemiological description of this epidemic was obtained from analysis of this data set. Using elementary mathematical analyses, we estimated the coverage of the detection system (percentage of HIV-positive adults detected and the average period between HIV infection and detection. Estimated HIV prevalence rates were corrected to account for the coverage. Results HIV prevalence has increased since 1996. In 2005, the prevalence among pregnant women was 1.2 per 10,000 (16/137000. Estimated HIV prevalence among 15- to 49-year-olds was 8.1 per 10,000 (4913/6065000; 95%CI: 7.9 per 10,000 – 8.3 per 10,000. Most (77% of the HIV-positive adults were men, most (85.1% of the detected HIV-positive men were reported as having sex with men (MSM, and most of the HIV-positive women reported having had sex with MSM. The average period between HIV infection and detection was estimated to be 2.1 years (IQR = 1.7 – 2.2 years. We estimated that, for the year 2005, 79.6% (IQR: 77.3 – 81.4% of the HIV-positive persons were detected. Conclusion MSM drive the HIV epidemic in Cuba. The extensive HIV testing policy may be an important factor in explaining the low HIV prevalence. To reduce the HIV epidemic in Cuba, the epidemic among MSM should be addressed. To understand this epidemic further, data on sexual behaviour should be collected. Now that

  5. New HIV Testing Algorithm: Promising Tool in the Fight Against HIV

    Centers for Disease Control (CDC) Podcasts

    In this podcast, CDC’s Dr. Phil Peters discusses the new HIV testing algorithm and how this latest technology can improve the diagnosis of acute HIV infection. Early detection of HIV is critical to saving lives, getting patients into treatment, and preventing transmission.

  6. HIV prevention intervention to reduce HIV-related stigma: evidence from China.

    Science.gov (United States)

    Li, Li; Liang, Li-Jung; Lin, Chunqing; Wu, Zunyou; Rotheram-Borus, Mary Jane

    2010-01-02

    The National Institute of Mental Health Collaborative HIV/Sexually Transmitted Disease Prevention Trial provided a unique opportunity to test whether, with the community-based diffusion of HIV/sexually transmitted disease prevention information and an elevated understanding of HIV, the level of stigmatizing attitudes toward people living with HIV/AIDS in the community would be reduced. A total of 4510 market workers in Fuzhou, China, participated in the study, and longitudinal analyses included study samples of 3785 participants in the 12-month follow-up and 3716 participants in the 24-month follow-up. We graphically examined the change in HIV-related stigma indicators over time between control and intervention groups using boxplot and kernel density estimation. A logistic regression analysis with proportional odds model was further used to examine the intervention effect on HIV-related stigmatizing attitudes. Compared with no change over time for the control group, the intervention successfully reduced the level of HIV-related stigmatizing attitudes among the target population at the 12-month follow-up, and the effect increased by two-fold (with respect to odds ratios) at the 24-month follow-up. The intervention demonstrated positive attitude changes associated with HIV-related stigma. Our results show the importance of social norms, rather than simply individual behaviors, in developing and implementing stigma reduction campaigns.

  7. Frequency of CCR5 Delta-32 Mutation in Human Immunodeficiency Virus (HIV-seropositive and HIV-exposed Seronegative Individuals and in General Population of Medellin, Colombia

    Directory of Open Access Journals (Sweden)

    Francisco J Díaz

    2000-04-01

    Full Text Available Repeated exposure to human immunodeficiency virus (HIV does not always result in seroconversion. Modifications in coreceptors for HIV entrance to target cells are one of the factors that block the infection. We studied the frequency of Delta-32 mutation in ccr5 gene in Medellin, Colombia. Two hundred and eighteen individuals distributed in three different groups were analyzed for Delta-32 mutation in ccr5 gene by polymerase chain reaction (PCR: 29 HIV seropositive (SP, 39 exposed seronegative (ESN and 150 individuals as a general population sample (GPS. The frequency of the Delta-32 mutant allele was 3.8% for ESN, 2.7% for GPS and 1.7% for SP. Only one homozygous mutant genotype (Delta-32/Delta-32 was found among the ESN (2.6%. The heterozygous genotype (ccr5/Delta-32 was found in eight GPS (5.3%, in one SP (3.4% and in one ESN (2.6%. The differences in the allelic and genotypic frequencies among the three groups were not statistically significant. A comparison between the expected and the observed genotypic frequencies showed that these frequencies were significantly different for the ESN group, which indirectly suggests a protective effect of the mutant genotype (Delta-32/Delta-32. Since this mutant genotype explained the resistance of infection in only one of our ESN persons, different mechanisms of protection must be playing a more important role in this population.

  8. Synthesis of amylose-block-polystyrene rod-coil block copolymers

    NARCIS (Netherlands)

    Loos, Katja; Stadler, Reimund

    1997-01-01

    In the present communication we demonstrate the synthesis of a hybrid block copolymer based on the combination of a biopolymer (amylose) with a synthetic block (polystyrene). To obtain such materials, amino-functionalized polymers were modified with maltoheptaose moieties that serve as initiators

  9. Neurological complication in HIV patients

    Science.gov (United States)

    Ritarwan, K.

    2018-03-01

    Human Immunodeficiency Virus (HIV) is neurotropic and immunotropic, making themassive destruction of both systems. Although their amount has been reduced, there is still neurological presentations and complications of HIV remain common in the era of combination antiretroviral therapy (cART). Neurological opportunistic infections (OI) occur in advanced HIV diseases such as primary cerebral lymphoma, cryptococcal meningitis, cerebral toxoplasmosis, and progressive multifocal encephalopathy. Neurological problem directly related to HIV appear at any stage in the progress of HIV disease, from AIDS-associated dementia to the aseptic meningitis of primary HIV infection observed in subjects with an immune deficiency. The replication of peripheral HIV viral is able to be controlled in the era of effective antiretroviral therapy. Non-HIV-related neurological disease such as stroke increased important as the HIV population ages.

  10. The HIV Airway

    African Journals Online (AJOL)

    Adele

    dren living with HIV/AIDS. Annual national antenatal surveil- lance shows an HIV prevalence of 26.5% among pregnant women. Anaesthetists are confronted with an increasing number of HIV infected patients, presenting for both emergency and elective sur- gery. They range from having asymptomatic infection to end stage.

  11. Programming of neurotoxic cofactor CXCL-10 in HIV-1-associated dementia: abrogation of CXCL-10-induced neuro-glial toxicity in vitro by PKC activator

    Directory of Open Access Journals (Sweden)

    Mehla Rajeev

    2012-10-01

    Full Text Available Abstract Background More than 50% of patients undergoing lifelong suppressive antiviral treatment for HIV-1 infection develop minor HIV-1-associated neurocognitive disorders. Neurological complications during HIV-1 infection are the result of direct neuronal damage by proinflammatory products released from HIV-1-infected or -uninfected activated lymphocytes, monocytes, macrophages, microglia and astrocytes. The specific pro-inflammatory products and their roles in neurotoxicity are far from clear. We investigated proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF of HIV-demented (HIV-D and HIV-nondemented (HIV-ND patients and studied their affect on neuroglial toxicity. Methods and results Bioplex array showed elevated levels of signatory chemokines or cytokines (IL-6, IFN-γ, CXCL10, MCP-1 and PDGF in the CSF of HIV-D patients (n = 7 but not in that of HIV-ND patients (n = 7. Among the signatory cytokines and chemokines, CXCL10 was distinctly upregulated in-vitro in HIV-1 (NLENG1-activated human fetal astrocytes, HIV-1 (Ba-L-infected macrophages, and HIV-1 (NLENG1-infected lymphocytes. Virus-infected macrophages also had increased levels of TNF-α. Consistently, human fetal astrocytes treated with HIV-1 and TNF-α induced the signatory molecules. CXCL10 in combination with HIV-1 synergistically enhanced neuronal toxicity and showed chemotactic activity (~ 40 fold for activated peripheral blood mononuclear cells (PBMC, suggesting the intersection of signaling events imparted by HIV-1 and CXCL10 after binding to their respective surface receptors, CXCR4 and CXCR3, on neurons. Blocking CXCR3 and its downstream MAP kinase (MAPK signaling pathway suppressed combined CXCL10 and HIV-1-induced neurotoxicity. Bryostatin, a PKC modulator and suppressor of CXCR4, conferred neuroprotection against combined insult with HIV-1 and CXCL10. Bryostatin also suppressed HIV-1 and CXCL10-induced PBMC chemotaxis. Although, therapeutic targeting

  12. Paravertebral Block Plus Thoracic Wall Block versus Paravertebral Block Alone for Analgesia of Modified Radical Mastectomy: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Nai-Liang Li

    Full Text Available Paravertebral block placement was the main anesthetic technique for modified radical mastectomy in our hospital until February 2014, when its combination with blocks targeting the pectoral musculature was initiated. We compared the analgesic effects of paravertebral blocks with or without blocks targeting the pectoral musculature for modified radical mastectomy.We retrospectively collected data from a single surgeon and anesthesiologist from June 1, 2012, to May 31, 2015. Intraoperative sedatives and analgesic requirements, time to the first analgesic request, postoperative analgesic doses, patient satisfaction, and complications were compared.Fifty-four patients received a paravertebral block alone (PECS 0, and 46 received a paravertebral block combined with blocks targeting the pectoral musculature (PECS 1. The highest intraoperative effect-site concentration of propofol was significantly lower in the PECS 1 group than in the PECS 0 group [2.3 (1.5, 2.8 vs 2.5 (1.5, 4 μg/mL, p = 0.0014]. The intraoperative rescue analgesic dose was significantly lower in the PECS 1 group [0 (0, 25 vs 0 (0, 75 mg of ketamine, p = 0.0384]. Furthermore, the PECS 1 group had a significantly longer time to the first analgesic request [636.5 (15, 720 vs 182.5 (14, 720 min, p = 0.0001]. After further adjustment for age, body mass index, American Society of Anesthesiologists Physical Status classification, chronic pain history, incidence of a superficial cervical plexus block placement, and operation duration, blocks targeting the pectoral musculature were determined to be the only significant factor (hazard ratio, 0.36; 95% confidence interval, 0.23-0.58; p < 0.0001. Very few patients used potent analgesics including morphine and ketorolac; the cumulative use of morphine or ketorolac was similar in the study groups. However, the incidence of all analgesic use, namely morphine, ketorolac, acetaminophen, and celecoxib, was significantly lower in the PECS 1 group [3

  13. Factors influencing HIV-risk behaviors among HIV-positive urban African Americans.

    Science.gov (United States)

    Plowden, Keith O; Fletcher, Audwin; Miller, J Lawrence

    2005-01-01

    Urban African Americans are disproportionately affected by HIV, the virus associated with AIDS. Although incidence and mortality appear to be decreasing in some populations, they continue to remain steady among inner-city African Americans. A major concern is the number of HIV-positive individuals who continue to practice high-risk behaviors. Understanding factors that increase risks is essential for the development and implementation of effective prevention initiatives. Following a constructionist epistemology, this study used ethnography to explore social and cultural factors that influence high-risk behaviors among inner-city HIV-positive African Americans. Leininger's culture care diversity and universality theory guided the study. Individual qualitative interviews were conducted with HIV-positive African Americans in the community to explore social and cultural factors that increase HIV-risky behaviors. For this study, family/kinship, economic, and education factors played a significant role in risky behaviors. Reducing HIV disparity among African Americans is dependent on designing appropriate interventions that enhance protective factors. Clinicians providing care to HIV-positive individuals can play a key role in reducing transmission by recognizing and incorporating these factors when designing effective prevention interventions.

  14. HIV Stigma, Retention in Care, and Adherence Among Older Black Women Living With HIV.

    Science.gov (United States)

    Sangaramoorthy, Thurka; Jamison, Amelia M; Dyer, Typhanye V

    Stigma is recognized as a barrier to the prevention, care, and treatment of HIV, including engagement in the HIV care continuum. HIV stigma in older Black women may be compounded by preexisting social inequities based on gender, age, and race. Using semi-structured interviews and survey questionnaires, we explore experiences of HIV stigma, retention in care, and antiretroviral therapy (ART) adherence in 35 older Black women with HIV from Prince George's County, Maryland. Study findings indicated that older Black women experienced high levels of HIV stigma, retention in care, and ART adherence. Findings suggest that experiences of HIV stigma were intensified for older Black women due to multiple stigmatized social positions. Participants also reported experiences of marginalization in health care that hindered retention in care and ART adherence. Interventions aimed at improving HIV prevention, care, and treatment outcomes should incorporate HIV stigma reduction strategies as core elements. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  15. CD4 Cell Counts at HIV Diagnosis among HIV Outpatient Study Participants, 2000–2009

    Directory of Open Access Journals (Sweden)

    Kate Buchacz

    2012-01-01

    Full Text Available Background. It is unclear if CD4 cell counts at HIV diagnosis have improved over a 10-year period of expanded HIV testing in the USA. Methods. We studied HOPS participants diagnosed with HIV infection ≤6 months prior to entry into care during 2000–2009. We assessed the correlates of CD4 count <200 cells/mm3 at HIV diagnosis (late HIV diagnosis by logistic regression. Results. Of 1,203 eligible patients, 936 (78% had a CD4 count within 3 months after HIV diagnosis. Median CD4 count at HIV diagnosis was 299 cells/mm3 and did not significantly improve over time (P=0.13. Comparing periods 2000-2001 versus 2008-2009, respectively, 39% and 35% of patients had a late HIV diagnosis (P=0.34. Independent correlates of late HIV diagnosis were having an HIV risk other than being MSM, age ≥35 years at diagnosis, and being of nonwhite race/ethnicity. Conclusions. There is need for routine universal HIV testing to reduce the frequency of late HIV diagnosis and increase opportunity for patient- and potentially population-level benefits associated with early antiretroviral treatment.

  16. Respiratory health status is impaired in UK HIV-positive adults with virologically suppressed HIV infection.

    Science.gov (United States)

    Brown, J; McGowan, J A; Chouial, H; Capocci, S; Smith, C; Ivens, D; Johnson, M; Sathia, L; Shah, R; Lampe, F C; Rodger, A; Lipman, M

    2017-09-01

    We sought to evaluate whether people living with HIV (PLWH) using effective antiretroviral therapy (ART) have worse respiratory health status than similar HIV-negative individuals. We recruited 197 HIV-positive and 93 HIV-negative adults from HIV and sexual health clinics. They completed a questionnaire regarding risk factors for respiratory illness. Respiratory health status was assessed using the St George's Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC) breathlessness scale. Subjects underwent spirometry without bronchodilation. PLWH had worse respiratory health status: the median SGRQ Total score was 12 [interquartile range (IQR) 6-25] in HIV-positive subjects vs. 6 (IQR 2-14) in HIV-negative subjects (P respiratory health appears more common in HIV-positive adults, and has a significant impact on health-related quality of life. © 2017 The Authors HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  17. Improving HIV proteome annotation: new features of BioAfrica HIV Proteomics Resource.

    Science.gov (United States)

    Druce, Megan; Hulo, Chantal; Masson, Patrick; Sommer, Paula; Xenarios, Ioannis; Le Mercier, Philippe; De Oliveira, Tulio

    2016-01-01

    The Human Immunodeficiency Virus (HIV) is one of the pathogens that cause the greatest global concern, with approximately 35 million people currently infected with HIV. Extensive HIV research has been performed, generating a large amount of HIV and host genomic data. However, no effective vaccine that protects the host from HIV infection is available and HIV is still spreading at an alarming rate, despite effective antiretroviral (ARV) treatment. In order to develop effective therapies, we need to expand our knowledge of the interaction between HIV and host proteins. In contrast to virus proteins, which often rapidly evolve drug resistance mutations, the host proteins are essentially invariant within all humans. Thus, if we can identify the host proteins needed for virus replication, such as those involved in transporting viral proteins to the cell surface, we have a chance of interrupting viral replication. There is no proteome resource that summarizes this interaction, making research on this subject a difficult enterprise. In order to fill this gap in knowledge, we curated a resource presents detailed annotation on the interaction between the HIV proteome and host proteins. Our resource was produced in collaboration with ViralZone and used manual curation techniques developed by UniProtKB/Swiss-Prot. Our new website also used previous annotations of the BioAfrica HIV-1 Proteome Resource, which has been accessed by approximately 10 000 unique users a year since its inception in 2005. The novel features include a dedicated new page for each HIV protein, a graphic display of its function and a section on its interaction with host proteins. Our new webpages also add information on the genomic location of each HIV protein and the position of ARV drug resistance mutations. Our improved BioAfrica HIV-1 Proteome Resource fills a gap in the current knowledge of biocuration.Database URL:http://www.bioafrica.net/proteomics/HIVproteome.html. © The Author(s) 2016. Published

  18. The New Kid on the Block--Incorporating Buprenorphine into a Medical Toxicology Practice.

    Science.gov (United States)

    Wiegand, Timothy J

    2016-03-01

    Buprenorphine represents a safe and effective therapy for treating opioid dependence, alleviating craving and withdrawal symptoms in opioid-dependent patients. Buprenorphine has a "blocking" effect against the action of other opioids at the mu-receptor, preventing not only opioid-induced euphoria, but CNS and respiratory depressant effects as well. Buprenorphine was approved for the treatment of opioid dependence in 2002 after the passage of Drug Abuse Treatment Act 2000 (DATA 2000) which allowed clinicians to treat opioid-dependent patients with specifically named opioid agonist therapies in an office setting. Buprenorphine programs reduce the prevalence of HIV and hepatitis C and reduce criminal behaviors associated with illicit drug use. Patients stabilized on buprenorphine have increased employment, enhanced engagement with social services, and better overall health and well-being.

  19. Laboratory Diagnosis Of Dual Hiv-1/Hiv-2 Infection In Ghanaian ...

    African Journals Online (AJOL)

    Objective: To determine the true prevalence of HIV dual infections in a previously characterised HIV seropositive patient group due to inconsistencies between different diagnostic methods. Design: A cross-sectional study of an HIV seropositive group with different diagnostic methods. Setting: Three hospitals in the Northern, ...

  20. Intra-facility linkage of HIV-positive mothers and HIV-exposed babies into HIV chronic care: rural and urban experience in a resource limited setting.

    Directory of Open Access Journals (Sweden)

    Christine Mugasha

    Full Text Available INTRODUCTION: Linkage of HIV-infected pregnant women to HIV care remains critical for improvement of maternal and child outcomes through prevention of maternal-to-child transmission of HIV (PMTCT and subsequent chronic HIV care. This study determined proportions and factors associated with intra-facility linkage to HIV care and Early Infant Diagnosis care (EID to inform strategic scale up of PMTCT programs. METHODS: A cross-sectional review of records was done at 2 urban and 3 rural public health care facilities supported by the Infectious Diseases Institute (IDI. HIV-infected pregnant mothers, identified through routine antenatal care (ANC and HIV-exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-delivery. RESULTS: Overall, 1,025 HIV-infected pregnant mothers were identified during ANC between January and June, 2012; 267/1,025 (26% in rural and 743/1,025 (74% in urban facilities. Of these 375/1,025 (37% were linked to HIV clinics [67/267(25% rural and 308/758(41% urban]. Of 636 HIV-exposed babies, 193 (30% were linked to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/636; 8/179 (4.5%] in rural and 93/457(20.3% in urban health facilities. Within rural facilities, ANC registration <28 weeks-of-gestation was associated with mothers' linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1-3.7, p = 0.019] and mothers' multi-parity was associated with baby's linkage to EID; AoR 4.4 (1.3-15.1, p = 0.023. Stigma, long distance to health facilities and vertical PMTCT services affected linkage in rural facilities, while peer mothers, infant feeding services, long patient queues and limited privacy hindered linkage to HIV care in urban settings. CONCLUSION: Post-natal linkage of HIV-infected mothers to chronic HIV care and HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary in urban and rural settings. We recommend targeted interventions to rapidly improve linkage to

  1. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.

  2. Influence of anchor block size on the thickness of adsorbed block copolymer layers

    NARCIS (Netherlands)

    Belder, G.F; ten Brinke, G.; Hadziioannou, G

    1997-01-01

    We present surface force data on three different polystyrene/poly(2-vinylpyridine) block copolymers (PS/P2VP) with a fixed size of the nonadsorbing PS block but widely varying sizes of the adsorbing P2VP block. With respect to the sizes of the two blocks, they range from moderately to highly

  3. HIV or HIV-Therapy? Causal attributions of symptoms and their impact on treatment decisions among women and men with HIV

    Directory of Open Access Journals (Sweden)

    Kremer H

    2009-04-01

    Full Text Available Abstract Objectives Among people with HIV, we examined symptom attribution to HIV or HIV-therapy, awareness of potential side effects and discontinuation of treatment, as well as sex/gender differences. Methods HIV-patients (N = 168, 46% female completed a comprehensive symptom checklist (attributing each endorsed symptom to HIV, HIV-therapy, or other causes, reported reasons for treatment discontinuations and potential ART-related laboratory abnormalities. Results Main symptom areas were fatigue/sleep/energy, depression/mood, lipodystrophy, and gastrointestinal, dermatological, and neurological problems. Top HIV-attributed symptoms were lack of stamina/energy in both genders, night sweats, depression, mood swings in women; and fatigue, lethargy, difficulties concentrating in men. Women attributed symptoms less frequently to HIV than men, particularly fa-tigue(p Top treatment-attributed symptoms were lipodystrophy and gastrointestinal problems in both genders. Symptom attribution to HIV-therapy did not differ between genders. Over the past six months, 22% switched/interrupted ART due to side effects. In women, side effect-related treatment decisions were more complex, involving more side effects and substances. Remarkably, women took predominantly protease inhibitor-sparing regimens (p = .05. Both genders reported only 15% of potential ART-related laboratory abnormalities but more than 50% had laboratory abnormalities. Notably, women had fewer elevated renal parameters (p Conclusions Men may attribute symptoms more often to HIV and maintain a treatment-regimen despite side effects, whereas women may be more prudent in avoiding treatment side effects. Lacking awareness of laboratory abnormalities in both genders potentially indicates gaps in physician-patient communication. Gender differences in causal attributions of symptoms/side effects may influence treatment decisions.

  4. Online resources for persons recently diagnosed with HIV/AIDS: an analysis of HIV-related webpages.

    Science.gov (United States)

    Horvath, Keith J; Harwood, Eileen M; Courtenay-Quirk, Cari; McFarlane, Mary; Fisher, Holly; Dickenson, Tina; Kachur, Rachel; Rosser, B R Simon; O'Leary, Ann

    2010-07-01

    The Internet is a major source of HIV-related information and resources for persons recently diagnosed with HIV/AIDS (PRDHA). This study examined the types of HIV-related websites that appear as a result of HIV-related keyword searches and the extent to which website information targets PRDHA. The first page of HIV-related webpages from 18 keyword searches was coded. Among 137 webpages meeting inclusion criteria, 63% represented HIV-informational websites, 31% targeted HIV-positive individuals, and over half contained or provided access to HIV prevention, treatment, and transmission information. Thirty-three percent of webpages contained or provided access to PRDHA-targeted information, with a greater percentage of those webpages having mobile, non-English, and "Ask the Expert" features compared with non-PRDHA targeted webpages. Implications for PRDHA include the following: (1) they should explore HIV-related websites to gain insight into the credibility of the information contained on those sites; (2) PRDHA must be aware that HIV-related websites have the potential to elicit dated, emotionally distressing, or irrelevant information; and (3) to obtain information that relates to their demographic and situational profile, they may wish to use specific key terms (e.g., "HIV women") rather than attempting to navigate webpages that arise from general search terms (e.g., "HIV"). Recommendations for future development of online resources for PRDHA include providing HIV-relevant information in a stepwise fashion, providing demographically targeted HIV information, and greater utilization of mobile technology.

  5. Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block

    Science.gov (United States)

    Franke, Manfred; Vrabec, Tina; Wainright, Jesse; Bhadra, Niloy; Bhadra, Narendra; Kilgore, Kevin

    2014-10-01

    Objective. Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. Approach. A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. Main results. The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. Significance. The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.

  6. The effects of HIV stigma on health, disclosure of HIV status, and risk behavior of homeless and unstably housed persons living with HIV.

    Science.gov (United States)

    Wolitski, Richard J; Pals, Sherri L; Kidder, Daniel P; Courtenay-Quirk, Cari; Holtgrave, David R

    2009-12-01

    HIV-related stigma negatively affects the lives of persons living with HIV/AIDS (PLWHA). Homeless/unstably housed PLWHA experience myriad challenges and may be particularly vulnerable to the effects of HIV-related stigma. Homeless/unstably housed PLWHA from 3 U.S. cities (N = 637) completed computer-assisted interviews that measured demographics, self-assessed physical and mental health, medical utilization, adherence, HIV disclosure, and risk behaviors. Internal and perceived external HIV stigma were assessed and combined for a total stigma score. Higher levels of stigma were experienced by women, homeless participants, those with a high school education or less, and those more recently diagnosed with HIV. Stigma was strongly associated with poorer self-assessed physical and mental health, and perceived external stigma was associated with recent non-adherence to HIV treatment. Perceived external stigma was associated with decreased HIV disclosure to social network members, and internal stigma was associated with drug use and non-disclosure to sex partners. Interventions are needed to reduce HIV-related stigma and its effects on the health of homeless/unstably housed PLWHA.

  7. Family physicians and HIV infection.

    Science.gov (United States)

    Hall, N; Crochette, N; Blanchi, S; Lavoix, A; Billaud, E; Baron, C; Abgueguen, P; Perré, P; Rabier, V

    2015-01-01

    We aimed to describe the current and desired involvement of family physicians (FPs) in the treatment of HIV patients (screening practices, potential training and patient follow-up) to reduce the duration and frequency of their hospital treatment. We conducted a descriptive cross-sectional survey between 2011 and 2012 with the support of COREVIH (Regional Coordinating Committee on HIV). We sent a self-assessment questionnaire to all FPs of the Pays de la Loire region to enquire about their HIV screening practices and expectations for the management of HIV patients. A total of 871 FPs completed the questionnaire (response rate: 30.4%). A total of 54.2% said to provide care to HIV patients; the mean number of HIV patients per FP was estimated at 1.4. With regard to HIV screening, 12.2% systematically suggest an HIV serology to their patients and 72.7% always suggest it to pregnant women. About 45.4% of responding FPs said to be willing to manage HIV patients (clinical and biological monitoring, compliance checks and prescription renewal). FPs mainly reported the lack of training and the low number of HIV patients as a barrier to their further involvement in the management of HIV patients. The responding FPs provide care to very few HIV patients. They are, however, willing to be more involved in the routine care of these patients. Medical training provided by COREVIH would help improve HIV screening. The management of HIV patients could thus be handed over to willing FPs. Copyright © 2015. Published by Elsevier SAS.

  8. Living with HIV/AIDS - Multiple Languages

    Science.gov (United States)

    ... HIV - Newly diagnosed with HIV, part 5 - English MP3 Children and HIV - Newly diagnosed with HIV, part 5 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Children and HIV - Newly diagnosed with HIV, part ...

  9. Epidemiological and Immunological Characteristics at the Time of HIV Diagnosis for HIV/AIDS Cohort Registrants Representative of HIV-Infected Populations in Korea

    OpenAIRE

    Lee, Jin-Hee; Kim, Seung Hyun; Wang, Jin-Sook; Sung, Kyoung Mi; Kim, Sung Soon; Kee, Mee-Kyung

    2012-01-01

    Objectives The Korea HIV/AIDS cohort was constructed with 18 hospitals that care for HIV-infected individuals in 2006. We compared the epidemiological and immunological characteristics of the cohort registrants with those of the HIVinfected population at the time of HIV diagnosis. Methods This study was conducted on 5717 people living with HIV/AIDS from 1985 to 2009, of which 789 individuals registered with the Korea HIV/AIDS cohort study. Individuals who had data from initial CD4+ T-cell cou...

  10. Cyclophilin A potentiates TRIM5α inhibition of HIV-1 nuclear import without promoting TRIM5α binding to the viral capsid.

    Directory of Open Access Journals (Sweden)

    Mallori Burse

    Full Text Available The host immunophilin cyclophilin A (CypA binds to the capsid protein (CA of HIV-1 and regulates its infectivity. Depending on the target cell type, CypA can either promote or inhibit HIV-1 infection. The ability of CypA to promote HIV-1 infection has been extensively studied and linked to several steps in early replication including uncoating, reverse transcription and nuclear import. By contrast, the mechanism by which CypA inhibits infection is less well understood. We investigated the mechanism by which CypA potentiates restriction of HIV-1 by the tripartite motif-containing protein 5 (TRIM5α. Depletion of TRIM5α in the African green monkey cell line Vero, resulted in a loss of inhibition of infection by CypA, demonstrating that inhibition by CypA is mediated by TRIM5α. Complementary genetic and biochemical assays failed to demonstrate an ability of CypA to promote binding of TRIM5α to the viral capsid. TRIM5α inhibits HIV-1 reverse transcription in a proteasome-dependent manner; however, we observed that inhibition of proteasome activity did not reduce the ability of CypA to inhibit infection, suggesting that CypA acts at a step after reverse transcription. Accordingly, we observed a CypA-dependent reduction in the accumulation of nuclear HIV-1 DNA, indicating that CypA specifically promotes TRIM5α inhibition of HIV-1 nuclear import. We also observed that the ability of CypA to inhibit HIV-1 infection is abolished by amino acid substitutions within the conserved CPSF6-binding surface in CA. Our results indicate that CypA inhibits HIV-1 infection in Vero cells not by promoting TRIM5α binding to the capsid but by blocking nuclear import of the HIV-1 preintegration complex.

  11. 42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

  12. HIV and travel.

    Science.gov (United States)

    Schuhwerk, M A; Richens, J; Zuckerman, Jane N

    2006-01-01

    There is a high demand for travel among HIV-positive individual. This demand arises partly from those who have benefited from advances in antiretroviral therapy as well as those with disease progression. The key to a successful and uneventful holiday lies in careful pre-trip planning, yet many patients fail to obtain advice before travelling. Travel advice for HIV patients is becoming increasingly specialized. In addition to advice on common travel-related infectious diseases, HIV-positive travellers are strongly advised to carry information with them and they need specific advice regarding country entry restrictions, HIV inclusive travel insurance, safety of travel vaccinations and highly active antiretroviral therapy-related issues. A wide range of relevant issues for the HIV-positive traveller are discussed in this review and useful websites can be found at the end.

  13. Abdominal wall blocks in adults

    DEFF Research Database (Denmark)

    Børglum, Jens; Gögenür, Ismail; Bendtsen, Thomas F

    2016-01-01

    been introduced with success. Future research should also investigate the effect of specific abdominal wall blocks on neuroendocrine and inflammatory stress response after surgery.  Summary USG abdominal wall blocks in adults are commonplace techniques today. Most abdominal wall blocks are assigned......Purpose of review Abdominal wall blocks in adults have evolved much during the last decade; that is, particularly with the introduction of ultrasound-guided (USG) blocks. This review highlights recent advances of block techniques within this field and proposes directions for future research.......  Recent findings Ultrasound guidance is now considered the golden standard for abdominal wall blocks in adults, even though some landmark-based blocks are still being investigated. The efficiency of USG transversus abdominis plane blocks in relation to many surgical procedures involving the abdominal wall...

  14. Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-07-01

    Full Text Available The nervous system plays an important role in HIV infection. The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF analysis in HIV infection in clinical practice. CSF analysis in HIV infection is indicated for the diagnosis of opportunistic infections and co-infections, diagnosis of meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS HIV compartmentalization. Although several CSF biomarkers have been investigated, none are clinically applicable. The capacity of HIV to generate genetic diversity, in association with the constitutional characteristics of the CNS, facilitates the generation of HIV quasispecies in the CNS that are distinct from HIV in the systemic circulation. CSF analysis has a well-defined and valuable role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is necessary to establish a clinically applicable biomarker for the diagnosis of HIV-associated neurocognitive disorders.

  15. Antimicrobial sensitivity pattern of Salmonella: comparison of isolates from HIV-infected and HIV-uninfected patients.

    Science.gov (United States)

    Wolday, D; Erge, W

    1998-07-01

    A retrospective analysis of all cases of Salmonella infections occurring between 1991 and 1995 was undertaken in order to evaluate the antimicrobial sensitivity pattern of the isolates from both human immunodeficiency virus (HIV) infected and uninfected Ethiopian patients. During the 5-year study period, we identified 147 cases of Salmonella infections. Only in 49 cases was the HIV serostatus known; 22 (44.9%) of the infections were in HIV seronegative patients while 27 (55.9%) were in HIV seropositive patients. The strains were isolated from blood (71.4%), urine (18.4%) and stool (8.2%). Salmonella infection was found to be more frequent (55.15% versus 44.9%) among HIV positive than HIV-negative patients. Moreover, Salmonella isolates recovered from HIV-seropositive patients were significantly resistant to many of the antibiotics tested when compared to the isolates from HIV-seronegative patients. The only chloramphenicol resistant Salmonella typhi occurred in a patient who was seropositive for HIV. According to these results, Ethiopian patients infected with HIV may be at risk of acquiring infections, especially non-typhoidal salmonellas, that are multi-drug resistant (MDR) strains than HIV-uninfected subjects. The emergence of MDR Salmonella infection among HIV-positive patients requires reassessment of chemotherapeutic approaches in this patient population, and warrants continued laboratory surveillance.

  16. Comparative study between ultrasound guided TAP block and paravertebral block in upper abdominal surgeries

    Directory of Open Access Journals (Sweden)

    Ruqaya M Elsayed Goda

    2017-01-01

    Conclusion: We concluded that ultrasound guided transverses abdominis plane block and thoracic paravertebral block were safe and effective anesthetic technique for upper abdominal surgery with longer and potent postoperative analgesia in thoracic paravertebral block than transverses abdominis block.

  17. Linkage to HIV care, postpartum depression, and HIV-related stigma in newly diagnosed pregnant women living with HIV in Kenya: a longitudinal observational study.

    Science.gov (United States)

    Turan, Bulent; Stringer, Kristi L; Onono, Maricianah; Bukusi, Elizabeth A; Weiser, Sheri D; Cohen, Craig R; Turan, Janet M

    2014-12-03

    While studies have suggested that depression and HIV-related stigma may impede access to care, a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV. However, this has not been investigated in postpartum women living with HIV. Furthermore, linkage to care itself may have additional impacts on postpartum depression beyond the effects of antiretroviral therapy. We examined associations between linkage to HIV care, postpartum depression, and internalized stigma in a population with a high risk of depression: newly diagnosed HIV-positive pregnant women. In this prospective observational study, data were obtained from 135 HIV-positive women from eight antenatal clinics in the rural Nyanza Province of Kenya at their first antenatal visit (prior to testing HIV-positive for the first time) and subsequently at 6 weeks after giving birth. At 6 weeks postpartum, women who had not linked to HIV care after testing positive at their first antenatal visit had higher levels of depression and internalized stigma, compared to women who had linked to care. Internalized stigma mediated the effect of linkage to care on depression. Furthermore, participants who had both linked to HIV care and initiated antiretroviral therapy reported the lowest levels of depressive symptoms. These results provide further support for current efforts to ensure that women who are newly diagnosed with HIV during pregnancy become linked to HIV care as early as possible, with important benefits for both physical and mental health.

  18. HIV prevention and low-income Chilean women: machismo, marianismo and HIV misconceptions.

    Science.gov (United States)

    Cianelli, Rosina; Ferrer, Lilian; McElmurry, Beverly J

    2008-04-01

    Socio-cultural factors and HIV-related misinformation contribute to the increasing number of Chilean women living with HIV. In spite of this, and to date, few culturally specific prevention activities have been developed for this population. The goal of the present study was to elicit the perspectives of low-income Chilean women regarding HIV and relevant socio-cultural factors, as a forerunner to the development of a culturally appropriate intervention. As part of a mixed-methods study, fifty low-income Chilean women participated in a survey and twenty were selected to participate in prevention, in-depth interviews. Results show evidence of widespread misinformation and misconceptions related to HIV/AIDS. Machismo and marianismo offer major barriers to prevention programme development. Future HIV prevention should stress partner communication, empowerment and improving the education of women vulnerable to HIV.

  19. HIV Stigma and Substance Use Among HIV-Positive Russians with Risky Drinking.

    Science.gov (United States)

    Edelman, E Jennifer; Lunze, Karsten; Cheng, Debbie M; Lioznov, Dmitry A; Quinn, Emily; Gnatienko, Natalia; Bridden, Carly; Chaisson, Christine E; Walley, Alexander Y; Krupitsky, Evgeny M; Raj, Anita; Samet, Jeffrey H

    2017-09-01

    The link between HIV stigma with substance use is understudied. We characterized individuals with high HIV stigma and examined whether HIV stigma contributes to substance use among HIV-positive Russians reporting risky alcohol use. We analyzed data from HERMITAGE, a randomized controlled trial of 700 people living with HIV/AIDS (PLWHA) with past 6-month risky sex and risky alcohol use in St. Petersburg, Russia (2007-2011). Participants who were female and reported depressive symptoms and lower social support were more likely to endorse high HIV stigma (all p's stigma was not significantly associated with the primary outcome unhealthy substance use and was not consistently associated with secondary substance use outcomes. Interventions to enhance social and mental health support for PLWHA, particularly women, may reduce stigma, though such reductions may not correspond to substantial decreases in substance use among this population.

  20. Pharmacodynamic Activity of Dapivirine and Maraviroc Single Entity and Combination Topical Gels for HIV-1 Prevention.

    Science.gov (United States)

    Dezzutti, Charlene S; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R; Rohan, Lisa C

    2015-11-01

    Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm(2)/min(1/2)), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm(2)/min(1/2)). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention.

  1. HIV pre-exposure prophylaxis for women and infants prevents vaginal and oral HIV transmission in a preclinical model of HIV infection.

    Science.gov (United States)

    Kovarova, Martina; Shanmugasundaram, Uma; Baker, Caroline E; Spagnuolo, Rae Ann; De, Chandrav; Nixon, Christopher C; Wahl, Angela; Garcia, J Victor

    2016-11-01

    Approximately 1.5 million HIV-positive women become pregnant annually. Without treatment, up to 45% will transmit HIV to their infants, primarily through breastfeeding. These numbers highlight that HIV acquisition is a major health concern for women and children globally. They also emphasize the urgent need for novel approaches to prevent HIV acquisition that are safe, effective and convenient to use by women and children in places where they are most needed. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine, a potent NRTI with low cytotoxicity, was administered orally to NOD/SCID/γc -/- mice and to bone marrow/liver/thymus (BLT) humanized mice, a preclinical model of HIV infection. HIV inhibitory activity in serum, cervicovaginal secretions and saliva was evaluated 4 h after administration. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine's ability to prevent vaginal and oral HIV transmission was evaluated using highly relevant transmitted/founder viruses in BLT mice. Strong HIV inhibitory activity in serum, cervicovaginal secretions and saliva obtained from animals after a single oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (10 mg/kg) demonstrated efficient drug penetration into relevant mucosal sites. A single daily oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine resulted in efficient prevention of vaginal and oral HIV transmission after multiple high-dose exposures to transmitted/founder viruses in BLT humanized mice. Our data demonstrated that 4'-ethynyl-2-fluoro-2'-deoxyadenosine efficiently prevents both vaginal and oral HIV transmission. Together with 4'-ethynyl-2-fluoro-2'-deoxyadenosine's relatively low toxicity and high potency against drug-resistant HIV strains, these data support further clinical development of 4'-ethynyl-2-fluoro-2'-deoxyadenosine as a potential pre-exposure prophylaxis agent to prevent HIV transmission in women and their infants. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial

  2. Validation of a self-reported HIV symptoms list: the ISS-HIV symptoms scale.

    Science.gov (United States)

    Bucciardini, Raffaella; Pugliese, Katherina; Francisci, Daniela; Costantini, Andrea; Schiaroli, Elisabetta; Cognigni, Miriam; Tontini, Chiara; Lucattini, Stefano; Fucili, Luca; Di Gregorio, Massimiliano; Mirra, Marco; Fragola, Vincenzo; Pompili, Sara; Murri, Rita; Vella, Stefano

    2016-01-01

    To describe the development and the psychometric properties of the Istituto Superiore di Sanità-HIV symptoms scale (lSS-HIV symptoms scale). The ISS-HIV symptom scale was developed by an Italian working team including researchers, physicians and people living with HIV. The development process went through the following steps: (1) review of HIV/AIDS literature; (2) focus group; (3) pre-test analysis; (4) scale validation. The 22 symptoms of HIV-ISS symptoms scale were clustered in five factors: pain/general discomfort (7 items); depression/anxiety (4 items); emotional reaction/psychological distress (5 items); gastrointestinal discomfort (4 items); sexual discomfort (2 items). The internal consistence reliability was for all factors within the minimum accepted standard of 0.70. The results of this study provide a preliminary evidence of the reliability and validity of the ISS-HIV symptoms scale. In the new era where HIV infection has been transformed into a chronic diseases and patients are experiencing a complex range of symptoms, the ISS-HIV symptoms scale may represent an useful tool for a comprehensive symptom assessment with the advantage of being easy to fill out by patients and potentially attractive to physicians mainly because it is easy to understand and requires short time to interpret the results.

  3. people who inject drugs, HIV risk, and HIV testing uptake in sub-Saharan Africa.

    Science.gov (United States)

    Asher, Alice K; Hahn, Judith A; Couture, Marie-Claude; Maher, Kelsey; Page, Kimberly

    2013-01-01

    Dramatic rises in injection drug use (IDU) in sub-Saharan Africa account for increasingly more infections in a region already overwhelmed by the HIV epidemic. There is no known estimate of the number of people who inject drugs (PWID) in the region, or the associated HIV prevalence in PWID. We reviewed literature with the goal of describing high-risk practices and exposures in PWID in sub-Saharan Africa, as well as current HIV prevention activities aimed at drug use. The literature search looked for articles related to HIV risk, injection drug users, stigma, and HIV testing in sub-Saharan Africa. This review found evidence demonstrating high rates of HIV in IDU populations in sub-Saharan Africa, high-risk behaviors of the populations, lack of knowledge regarding HIV, and low HIV testing uptake. There is an urgent need for action to address IDU in order to maintain recent decreases in the spread of HIV in sub-Saharan Africa. Copyright © 2013 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  4. Toward Automating HIV Identification: Machine Learning for Rapid Identification of HIV-Related Social Media Data.

    Science.gov (United States)

    Young, Sean D; Yu, Wenchao; Wang, Wei

    2017-02-01

    "Social big data" from technologies such as social media, wearable devices, and online searches continue to grow and can be used as tools for HIV research. Although researchers can uncover patterns and insights associated with HIV trends and transmission, the review process is time consuming and resource intensive. Machine learning methods derived from computer science might be used to assist HIV domain experts by learning how to rapidly and accurately identify patterns associated with HIV from a large set of social data. Using an existing social media data set that was associated with HIV and coded by an HIV domain expert, we tested whether 4 commonly used machine learning methods could learn the patterns associated with HIV risk behavior. We used the 10-fold cross-validation method to examine the speed and accuracy of these models in applying that knowledge to detect HIV content in social media data. Logistic regression and random forest resulted in the highest accuracy in detecting HIV-related social data (85.3%), whereas the Ridge Regression Classifier resulted in the lowest accuracy. Logistic regression yielded the fastest processing time (16.98 seconds). Machine learning can enable social big data to become a new and important tool in HIV research, helping to create a new field of "digital HIV epidemiology." If a domain expert can identify patterns in social data associated with HIV risk or HIV transmission, machine learning models could quickly and accurately learn those associations and identify potential HIV patterns in large social data sets.

  5. The relationship of reported HIV risk and history of HIV testing among emergency department patients.

    Science.gov (United States)

    Merchant, Roland C; Freelove, Sarah M; Langan, Thomas J; Clark, Melissa A; Mayer, Kenneth H; Seage, George R; DeGruttola, Victor G

    2010-01-01

    Among a random sample of emergency department (ED) patients, we sought to determine the extent to which reported risk for human immunodeficiency virus (HIV) is related to ever having been tested for HIV. A random sample of patients (aged 18-64 years) from an adult, urban, northeastern United States, academic ED were surveyed about their history of ever having been tested for HIV and their reported HIV risk behaviors. A reported HIV risk score was calculated from the survey responses and divided into 4 levels, based on quartiles of the risk scores. Pearson's X(2) testing was used to compare HIV testing history and level of reported HIV risk. Logistic regression models were created to investigate the association between level of reported HIV risk and the outcome of ever having been tested for HIV. Of the 557 participants, 62.1% were female. A larger proportion of females than males (71.4% vs 60.6%; P history of injection-drug use, were associated with prior HIV testing for both genders. In the logistic regression analyses, there was no relationship between increasing level of reported HIV risk and a history of ever having been tested for HIV for males. For females, a history of ever having been tested was related to increasing level of reported risk, but not in a linear fashion. The relationship between reported HIV risk and history of testing among these ED patients was complex and differed by gender. Among these patients, having greater risk did not necessarily mean a higher likelihood of ever having been tested for HIV.

  6. Fermion-scalar conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Iliesiu, Luca [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States); Kos, Filip [Department of Physics, Yale University,217 Prospect Street, New Haven, CT 06520 (United States); Poland, David [Department of Physics, Yale University,217 Prospect Street, New Haven, CT 06520 (United States); School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, New Jersey 08540 (United States); Pufu, Silviu S. [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States); Simmons-Duffin, David [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, New Jersey 08540 (United States); Yacoby, Ran [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States)

    2016-04-13

    We compute the conformal blocks associated with scalar-scalar-fermion-fermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. Conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  7. HIV-related disabilities: an extra burden to HIV and AIDS healthcare ...

    African Journals Online (AJOL)

    Background: Healthcare workers have been at the forefront of dealing with the impact of HIV and AIDS at all stages of the pandemic. This brings new challenges to include disability into HIV care. However, the implications for healthcare workers in an already fragile health system along with HIV-related disabilities in ...

  8. Block Cipher Analysis

    DEFF Research Database (Denmark)

    Miolane, Charlotte Vikkelsø

    ensurethat no attack violatesthe securitybounds specifiedbygeneric attack namely exhaustivekey search and table lookup attacks. This thesis contains a general introduction to cryptography with focus on block ciphers and important block cipher designs, in particular the Advanced Encryption Standard(AES...... on small scale variants of AES. In the final part of the thesis we present a new block cipher proposal Present and examine its security against algebraic and differential cryptanalysis in particular....

  9. Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients

    Science.gov (United States)

    Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

    2015-01-01

    Abstract Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups. We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors. Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P HIV-infected patients. However, heartburn and acid regurgitation were independently (P symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... contracting or transmitting HIV/AIDS or other infectious diseases. Research Reports: HIV/AIDS : Explores the link between drug misuse and HIV/AIDS, populations most at risk, trends in HIV/AIDS, and ...

  11. The Amagugu Intervention: A conceptual framework for increasing HIV disclosure and parent-led communication about health and HIV prevention among HIV-infected parents with HIV-uninfected primary school-aged children

    Directory of Open Access Journals (Sweden)

    Tamsen Jean Rochat

    2016-08-01

    Full Text Available Advances in access to HIV prevention and treatment have reduced vertical transmission of HIV, with most children born to HIV-infected parents being HIV-uninfected themselves. A major challenge that HIV-infected parents face is disclosure of their HIV status to their predominantly HIV-uninfected children. Their children enter middle childhood and early adolescence facing many challenges associated with parental illness and hospitalisation, often exacerbated by stigma and a lack of access to health education and support. Increasingly, evidence suggests that primary school-aged children have the developmental capacity to grasp concepts of health and illness, including HIV, and that in the absence of parent-led communication and education about these issues, HIV-exposed children may be at increased risk of psychological and social problems. The Amagugu intervention is a six-session home-based intervention, delivered by lay counsellors, which aims to increase parenting capacity to disclose their HIV status and offer health education to their primary school-aged children. The intervention includes information and activities on disclosure, health care engagement and custody planning. An uncontrolled pre-post evaluation study with 281 families showed the intervention was feasible, acceptable and effective in increasing maternal disclosure. The aim of this manuscript is to describe the conceptual model of the Amagugu intervention, as developed post-evaluation, showing the proposed pathways of risk that Amagugu aims to disrupt through its intervention targets, mechanisms and activities; and to present a summary of results from the large scale evaluation study of Amagugu to demonstrate the acceptability and feasibility of the intervention model. This relatively low-intensity home-based intervention led to: increased HIV disclosure to children, improvements in mental health for mother and child, and improved health care engagement and custody planning for

  12. Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype.

    Science.gov (United States)

    Patterson, B K; Mosiman, V L; Cantarero, L; Furtado, M; Bhattacharya, M; Goolsby, C

    1998-04-01

    Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.

  13. HIV-related symptoms and patient clusters among Chileans living with HIV.

    Science.gov (United States)

    Araya, A X; Norr, K F; Pérez, C M; Levy, J A; Park, C G; Kim, M J

    2013-01-01

    Identifying both Human immunodeficiency virus (HIV)-related and co-morbid symptoms experienced by people living with HIV (PLWH) who are receiving antiretroviral therapy (ART) treatment is a major challenge for healthcare providers globally. Yet, little research to date has examined the symptoms of illness experienced by PLWH including patients living in Central and South American. To address this gap, this study was designed to identify symptoms of HIV by socio-demographic and/or clinical characteristics among Chilean patients living with the virus. A convenience sample of 209 Chilean PLWH was recruited from an outpatient clinic in Santiago, Chile. A structured interview was used to elicit socio-demographic information and HIV symptoms status. Additional clinical information was obtained through a review of the participants' medical records. Results show that patients' most commonly reported HIV-related symptoms were fear/worries (66%), anxiety (52%), gas/bloating (50%), and thirst (50%). Multivariate analysis revealed a positive association between the number of reported HIV-related symptoms and number of years living with HIV. Having completed college was negatively associated with number of symptoms. Latent class analysis indicated that PLWH in the sample who had completed college were two times more likely to experience a mild intensity of HIV-related symptoms than their lesser educated counterparts. Similarly, logistic regression revealed that college-educated PLWH were twice as likely to be classified in the subgroup reporting mild intensity of symptoms than those who lacked a college degree. Overall, the study's results reveal that many Chilean PLWH, even those with high CD4 counts and low or undetectable viral loads, are not symptom free. The findings point to the need for clinicians to tailor a plan of care for individuals living with HIV that is based on their symptomatology.

  14. Main-chain supramolecular block copolymers.

    Science.gov (United States)

    Yang, Si Kyung; Ambade, Ashootosh V; Weck, Marcus

    2011-01-01

    Block copolymers are key building blocks for a variety of applications ranging from electronic devices to drug delivery. The material properties of block copolymers can be tuned and potentially improved by introducing noncovalent interactions in place of covalent linkages between polymeric blocks resulting in the formation of supramolecular block copolymers. Such materials combine the microphase separation behavior inherent to block copolymers with the responsiveness of supramolecular materials thereby affording dynamic and reversible materials. This tutorial review covers recent advances in main-chain supramolecular block copolymers and describes the design principles, synthetic approaches, advantages, and potential applications.

  15. Associations between HIV and schizophrenia and their effect on HIV treatment outcomes

    DEFF Research Database (Denmark)

    Helleberg, Marie; Pedersen, Marianne G; Pedersen, Carsten B

    2015-01-01

    BACKGROUND: Associations between HIV and schizophrenia in people with and without substance use disorders and the effect on timeliness of HIV diagnosis, antiretroviral therapy (ART), and treatment outcomes are poorly understood. We aimed to assess the association between HIV and schizophrenia and...

  16. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

    2017-01-01

    Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

  17. RCT of an integrated CBT-HIV intervention on depressive symptoms and HIV risk.

    Science.gov (United States)

    Tobin, Karin; Davey-Rothwell, Melissa A; Nonyane, Bareng A S; Knowlton, Amy; Wissow, Lawrence; Latkin, Carl A

    2017-01-01

    Depression and depressive symptoms mediate the association between drug use and HIV risk. Yet, there are few interventions that target depressive symptoms and HIV risk for people who use drugs (PWUD). This study was a randomized controlled trial of an integrated cognitive behavioral therapy and HIV prevention intervention to reduce depressive symptoms, injection risk behaviors and increase condom use in a sample of urban people who used heroin or cocaine in the prior 6 months. A total of 315 individuals aged 18-55, who self-reported at least one HIV drug and sex risk behavior and scored ≥16 and symptoms, but weak impact on HIV risk. This trial is registered with ClinicalTrials.gov under the title "Neighborhoods, Networks, Depression, and HIV Risk" number NCT01380613.

  18. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  19. Interaction between HIV awareness, knowledge, safe sex practice and HIV prevalence: evidence from Botswana.

    Science.gov (United States)

    Ray, Ranjan; Sinha, Kompal

    2012-05-01

    This paper makes methodological and empirical contributions to the study of HIV in the context of Botswana, a country with high HIV prevalence. Comparable evidence is presented from India to put the Botswana results in perspective. The results point to the strong role played by affluence and education in increasing HIV knowledge, promoting safe sex and reducing HIV prevalence. The study presents African evidence on the role played by the empowerment of women in promoting safe sex practices such as condom use. The lack of significant association between HIV prevalence and safe sex practice points to the danger of HIV-infected individuals spreading the disease through multiple sex partners and unprotected sex. This danger is underlined by the finding that females with multiple sex partners are at higher risk of being infected with HIV. These results take on special policy significance in the context of Botswana, where the issue of multiple sex partners has not been adequately addressed in the programme to contain the spread of HIV.

  20. Exposure to apoptotic activated CD4+ T cells induces maturation and APOBEC3G-mediated inhibition of HIV-1 infection in dendritic cells.

    Directory of Open Access Journals (Sweden)

    Venkatramanan Mohanram

    Full Text Available Dendritic cells (DCs are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4(+ T cells (ApoInf or apoptotic uninfected activated CD4(+ T cells (ApoAct induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4(+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1α, MIP-1β, MCP-1, and TNF-α; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-α using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4(+ T cells (ApoRest. Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection.

  1. Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061.

    Directory of Open Access Journals (Sweden)

    Iris Chen

    Full Text Available HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.A high resolution melting (HRM diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm, and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study visits.Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions and HIV drug resistance (both gag regions were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment.HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.

  2. [Enhanced prenatal HIV couple oriented counselling session and couple communication about HIV (ANRS 12127 Prenahtest Trial)].

    Science.gov (United States)

    Plazy, M; Orne-Gliemann, J; Balestre, E; Miric, M; Darak, S; Butsashvili, M; Tchendjou, P; Dabis, F; Desgrées du Loû, A

    2013-08-01

    The Prenahtest study investigated the efficacy of a couple-oriented HIV counselling session (COC) in encouraging couple HIV counselling and testing, and improving intra-couple communication about sexual and reproductive health. We report here on the effect of COC on intra-couple communication about HIV. Within this 4-country trial (India, Georgia, Dominican Republic and Cameroon), 484 to 491 pregnant women per site were recruited and individually randomized to receive either the COC intervention, enhanced counselling with role playing, or standard post-test HIV counselling. Women were interviewed at recruitment, before HIV testing (T0), and 2 to 8 weeks after post-test HIV counselling (T1). Four dichotomous variables documented intra-couple communication about HIV at T1: 1) discussion about HIV, 2) discussion about condom use, 3) suggesting HIV testing and 4) suggesting couple HIV counselling to the partner. An intra-couple HIV communication index was created: low degree of communication ("yes" response to zero or one of the four variables), intermediate degree of communication ("yes" to two or three variables) or high degree of communication ("yes" to the four variables). To estimate the impact of COC on the intra-couple HIV communication index, multivariable logistic regressions were conducted. One thousand six hundred and seven women were included in the analysis of whom 54 (3.4%) were HIV-infected (49 in Cameroon). In the four countries, the counselling group was associated with intra-couple HIV communication (P≤0.03): women allocated to the COC group were significantly more likely to report high or intermediate degrees of intra-couple communication about HIV (versus low degree of communication) than women allocated to standard counselling. COC improved short-term communication about HIV within couples in different sociocultural contexts, a positive finding for a couple approach to HIV prevention. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... What do I need to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and ... Should an HIV patient be tested for pulmonary hypertension? HIV patients know that medical supervision is critical ...

  4. HIV Co-receptor usage in HIV-related non-hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Reid Erin

    2012-03-01

    Full Text Available Abstract In this study 15 banked samples of HIV-related Non-Hodgkin's Lymphoma (NHL cases were tested for HIV co-receptor usage and SDF1 3'A polymorphism. Reportable tropism from 9 plasma samples had 1 (11.1% HIV case with CXCR4 and 8 (88.9% with CCR5 usage, even though most of the cases occurred at a late stage of HIV (2/3 had CD4 counts below 200, where expected CXCR4 usage would be 60%. Based on the expected proportion of less than 50% CCR5 in chronically infected individuals, this would suggest that in NHL may be associated with CCR5 usage (P = 0.04.

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, National ...

  6. HIV / AIDS: An Unequal Burden

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 ... high-risk category, emphasizes Dr. Cargill. Photo: iStock HIV and Pregnancy Are there ways to help HIV- ...

  7. NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope.

    Science.gov (United States)

    Perfettini, Jean-Luc; Roumier, Thomas; Castedo, Maria; Larochette, Nathanael; Boya, Patricia; Raynal, Brigitte; Lazar, Vladimir; Ciccosanti, Fabiola; Nardacci, Roberta; Penninger, Josef; Piacentini, Mauro; Kroemer, Guido

    2004-03-01

    The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-kappaB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor kappaB (NF-kappaB) super repressor had an antimitotic and antiapoptotic effect and prevented the Env-elicited phosphorylation of p53 on serine 15 and 46, as well as the activation of AP1. Transfection with dominant-negative p53 abolished apoptosis and AP1 activation. Signs of NF-kappaB and p53 activation were also detected in lymph node biopsies from HIV-1-infected individuals. Microarrays revealed that most (85%) of the transcriptional effects of HIV-1 Env were blocked by the p53 inhibitor pifithrin-alpha. Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak. Down modulation of Puma by antisense oligonucleotides, as well as RNA interference of Bax and Bak, prevented Env-induced apoptosis. HIV-1-infected primary lymphoblasts up-regulated Puma in vitro. Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy. Altogether, these data indicate that NF-kappaB and p53 cooperate as the dominant proapoptotic transcription factors participating in HIV-1 infection.

  8. Internalized stigma and HIV status disclosure among HIV-positive black men who have sex with men.

    Science.gov (United States)

    Overstreet, Nicole M; Earnshaw, Valerie A; Kalichman, Seth C; Quinn, Diane M

    2013-01-01

    Black men who have sex with men (BMSM) are severely affected by the HIV epidemic, yet research on the relationship between HIV stigma and status disclosure is relatively limited among this population. Within this epidemic, internalized HIV stigma, the extent to which people living with HIV/AIDS endorse the negative beliefs associated with HIV as true of themselves, can negatively shape interpersonal outcomes and have important implications for psychological and physical health. In a sample of HIV-positive BMSM (N=156), the current study examined the effect of internalized stigma on HIV status disclosure to sexual partners, which can inform sexual decision-making in serodiscordant couples, and HIV status disclosure to family members, which can be beneficial in minimizing the psychological distress associated with HIV. Results revealed that greater internalized stigma was associated with less HIV status disclosure to participants' last sexual partner and to family members. Findings from this study provide evidence that internalized negative beliefs about one's HIV status are linked to adverse interpersonal consequences. Implications of these findings are discussed with regard to prevention and intervention efforts to reduce HIV stigmatization.

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the ...

  10. HIV-related symptoms and management in HIV and antiretroviral ...

    African Journals Online (AJOL)

    Karl Peltzer

    2014-01-03

    Jan 3, 2014 ... To cite this article: Karl Peltzer (2013) HIV-related symptoms and management in HIV and antiretroviral therapy patients ...... Fear/worry. 14.2. 22. 2.5. 20 ..... Internalized Stigma, Discrimination, and Depression among Men and.

  11. Cardiovascular Diseases in HIV-infected Subjects (HIV-HEART Study)

    Science.gov (United States)

    2010-05-07

    Detection of Frequency, Severity and Progression of Cardiovascular Diseases in Patients With HIV-infection.; Effect on Cardiovascular Risk and Life Quality by Age, Gender, Classic Cardiovascular Risk Factors,; HIV-specific Cardiovascular Risk Factors, Cardiovascular Medication, Antiretroviral Medication

  12. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections.

    Science.gov (United States)

    Suligoi, Barbara; Regine, Vincenza; Raimondo, Mariangela; Rodella, Anna; Terlenghi, Luigina; Caruso, Arnaldo; Bagnarelli, Patrizia; Capobianchi, Maria Rosaria; Zanchetta, Nadia; Ghisetti, Valeria; Galli, Claudio

    2017-10-26

    Detecting recent HIV infections is important to evaluate incidence and monitor epidemic trends. We aimed to evaluate the diagnostic performance and accuracy of the avidity index (AI) for discriminating for recent HIV infections. We collected serum samples from HIV-1 positive individuals: A) with known date of infection (midpoint in time between last HIV-negative and first HIV-positive test); B) infected for >1 year. Samples were divided into two aliquots: one diluted with phosphate buffered saline (PBS) and the other with 1 M guanidine. Both aliquots were assayed by the Architect HIV Ag/Ab Combo 4th generation assay (Abbott). We compared AI found in recent (RI=HIV subtype had no impact on AI misclassifications. All individuals in group A reached the AI threshold of 0.80 within 24 months after seroconversion. The AI is an accurate serological marker for discriminating recent from established HIV infections and meets WHO requirements for HIV incidence assays.

  13. HIV/HCV Coinfection in Taiwan.

    Science.gov (United States)

    Hsu, Ching-Sheng; Kao, Jia-Horng

    2016-01-01

    Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are important global public health problems with shared transmission routes. Although HIV/HCV coinfection is not uncommon, the prevalence rates vary significantly across different studies and regions. In Taiwan, injection drug users have become the major contributors to the HIV/AIDS epidemic since 2005. Because the prevalence of HCV infection is high in injection drug users, this HIV epidemic is also associated with a significant increase of HIV/HCV coinfection in Taiwan. To control Taiwan's HIV epidemic, Taiwan Centers for Disease Control (CDC) launched a harm-reduction program in 2006. The HIV epidemic, the percentage attributed to injection drug users, and the prevalence of HIV/HCV coinfection gradually declined thereafter. In this article, we aimed to thoroughly examine the current literatures of HIV/HCV coinfection in Taiwan and hope to provide a better understanding of the needs for the management of this coinfection. We conducted a narrative review and searched for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database untill August 2015. Studies relevant to the epidemiology and associated risk factors of HIV/HCV coinfection in Taiwan were examined and discussed.

  14. [Prevalence and related factors of HIV/HBV coinfection among HIV/AIDS patients].

    Science.gov (United States)

    Feng, D; Yao, T; Cheng, Y P; Pan, M H; Li, C X; Wang, J; Feng, Y L; Shi, J; Huang, H L; Lu, H Y; Lan, G H; Wang, S P; Zhang, Y W

    2017-12-10

    Objective: To reveal the prevalence and the related factors of hepatitis B (HepB) virus infection among HIV/AIDS patients. Methods: We conducted a cross-sectional study in two HIV clinics, affiliated to local Centers of Disease Control and Prevention in Guangxi Zhuang Autonomous Regional. A face-to-face interview, with questionnaire was conducted to collect information on socio-demographic characteristics, drug use, and sexual behavior. Blood samples were used to test HBsAg. χ (2) test or Fisher's exact test and unconditional logistic regression models were used to identify the influencing factors. Results: The prevalence of HBV and HIV co-infection was 13.85% (113/816). Results from multivariate logistic regression analyses showed that age (25-45), family history of HBV and history of HepB vaccination were independent influencing factors for HBV and HIV coinfection, with OR (95% CI ) as 1.738 (1.031-2.931), 2.898 (1.678-5.005) and 1.744 (1.052-2.892), respectively. Conclusion: The prevalence of HBV among HIV/AIDS patients was significantly higher than that in general population. HIV/AIDS patients aged between 25 and 45 and with family history of HBV were more likely to be infected with HBV, while HepB vaccination was associated with the reduction of HIV/HBV coinfection. Specific comprehensive prevention and treatment programs on HIV/AIDS patients need to be set up.

  15. Prevalence of HIV associated neurocognitive deficit among HIV ...

    African Journals Online (AJOL)

    Background: HIV associated neurocognitive deficit impairs motor activity, neuropsychiatric functioning, daily activity and work activity usually due to the immune suppression effect of the virus. Sub-Saharan region including Ethiopia is the region with the highest burden of HIV. However, a few studies are found on this aspect ...

  16. Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

    Science.gov (United States)

    Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Goujard, Cécile; Deveau, Christiane; Meyer, Laurence; Ngo, Nicole; Rouzioux, Christine; Guillet, Jean-Gérard; Delfraissy, Jean-François; Sinet, Martine; Venet, Alain

    1999-01-01

    HIV-specific CD8+ T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8+ T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0–6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1–13). The frequency of HIV-specific CD8+ T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8+CD28– terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination. J. Clin. Invest. 104:1431–1439 (1999). PMID:10562305

  17. Compromiso renal en pacientes HIV+ Renal abnormalities in HIV infected patients

    Directory of Open Access Journals (Sweden)

    María Marta Pernasetti

    2010-06-01

    Full Text Available Varias complicaciones nefrológicas pueden ocurrir durante la infección por el virus de la inmunodeficiencia humana (HIV especialmente en estadios avanzados de la enfermedad o relacionadas con otras infecciones o drogas. Poco conocida es la prevalencia de alteraciones renales subclínicas de pacientes HIV+ surgidas como complicación o relacionadas a la infección y/o tratamiento. Realizamos un corte transversal de pacientes asintomáticos HIV+ referidos en forma consecutiva al consultorio de nefrología para la detección de alteraciones nefrológicas. Se estudiaron 52 pacientes adultos mediante exámenes de sangre y orina, ultrasonido y biopsia renal. Edad media 39.9 ± 10.6 años, 88% varones, tiempo de diagnóstico de la infección: 53.2 ± 41.2 (2-127 meses. El 71% tenían síndrome de inmunodeficiencia adquirida (HIV-sida y el 77% recibían con antirretrovirales. La carga viral al momento del estudio fue 7043 ± 3322 copias y el recuento de CD4+ 484 ± 39 cel/mm³. El 30.7% presentó alteraciones del sedimento urinario: albuminuria: 16.6%, hematuria microscópica: 11.5%, hipercalciuria: 10.8% y cristaluria 6%. La media del filtrado glomerular fue 102.2 ± 22.9 ml/min (rango: 34-149. El 41% presentó anormalidades que corresponderían a enfermedad renal crónica (estadios 1 a 3. Los pacientes con alteraciones tenían mayor edad, con duración más prolongada de la infección. Las anomalías renales no se asociaron con mayor prevalencia de HIV-sida. Dos pacientes fueron biopsiados, con hallazgos de nefritis túbulo-intersticial crónica con cristales y glomerulonefritis por IgA. No hubo hallazgos de nefropatía por HIV. El amplio espectro y la alta prevalencia de anormalidades nefrológicas subclínicas encontradas sugieren que los pacientes asintomáticos HIV+ deberían realizar evaluaciones nefrológicas de rutina.Several renal complications may occur during HIV infection, especially in advanced stages related to HIV, to other infectious

  18. Facilitators and barriers to discussing HIV prevention with adolescents: perspectives of HIV-infected parents.

    Science.gov (United States)

    Edwards, Laura L; Reis, Janet S; Weber, Kathleen M

    2013-08-01

    We examined HIV-infected parents' conversations about HIV prevention with their uninfected children, including what facilitated or hindered communication. Parents with HIV/AIDS (n = 90) who had children aged 10 to 18 years were recruited for a mixed method study from 2009 to 2010. Interviews assessed facilitators and barriers to discussing HIV prevention. A questionnaire identified the frequency and content of conversations, parental confidence level, and perceived importance of discussing preventive topics. Eighty-one percent of parents reported "sometimes" or "often" communicating about HIV prevention. A subset of parents found these conversations difficult; 44% indicated their desire for support. Facilitators to communication included utilizing support, focusing on the benefits of talking, and having a previous relationship with one's child. Barriers to discussions included fear of negative consequences, living in denial, and lacking a parental role model who discussed safer sex. Parents varied as to how they believed their HIV status affected communication. Those who did not disclose their HIV status to their children reported less frequent communication; self-efficacy partially mediated this relationship. Findings highlighted the need for communication skills training that support HIV-infected parents in their efforts to discuss HIV-related information with adolescents.

  19. HIV/AIDS and Alcohol

    Science.gov (United States)

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). The U.S. CDC reported that in 2015, 39, ...

  20. Adding an Artificial Tail—Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile

    Directory of Open Access Journals (Sweden)

    Shan Su

    2017-11-01

    Full Text Available Peptides derived from the C-terminal heptad repeat (CHR of human immunodeficiency virus type 1 (HIV-1 envelope protein transmembrane subunit gp41, such as T20 (enfuvirtide, can bind to the N-terminal heptad repeat (NHR of gp41 and block six-helix bundle (6-HB formation, thus inhibiting HIV-1 fusion with the target cell. However, clinical application of T20 is limited because of its low potency and genetic barrier to resistance. HP23, the shortest CHR peptide, exhibits better anti-HIV-1 activity than T20, but the HIV-1 strains with E49K mutations in gp41 will become resistant to it. Here, we modified HP23 by extending its C-terminal sequence using six amino acid residues (E6 and adding IDL (Ile-Asp-Leu to the C-terminus of E6, which is expected to bind to the shallow pocket in the gp41 NHR N-terminal region. The newly designed peptide, designated HP23-E6-IDL, was about 2- to 16-fold more potent than HP23 against a broad spectrum of HIV-1 strains and more than 12-fold more effective against HIV-1 mutants resistant to HP23. These findings suggest that addition of an anchor–tail to the C-terminus of a CHR peptide will allow binding with the pocket in the gp41 NHR that may increase the peptide’s antiviral efficacy and its genetic barrier to resistance.

  1. Nutrition and HIV-Positive Pregnancy

    OpenAIRE

    Montgomery, Kristen S.

    2003-01-01

    When an HIV-positive woman becomes pregnant, additional nutritional considerations are warranted. Compared to routine prenatal nutritional assessment and intervention, pregnant HIV-positive women have increased needs to promote a healthy outcome. This column contains information on HIV and pregnancy, nutrition and infection, and nutrition for HIV-positive pregnancy. This content can be integrated into childbirth education settings to improve care to women who are HIV-positive.

  2. Working Memory Profiles in HIV-Exposed, Uninfected and HIV-Infected Children: A Comparison with Neurotypical Controls

    Science.gov (United States)

    Milligan, Robyn; Cockcroft, Kate

    2017-01-01

    This study compared the working memory profiles of three groups of children, namely HIV-infected (HIV-I; n = 95), HIV-exposed, uninfected (HIV-EU; n = 86) and an HIV-unexposed, uninfected, (HIV-UU; n = 92) neurotypical control group. Working memory, an executive function, plays an important role in frontal lobe-controlled behaviors, such as motivation, planning, decision making, and social interaction, and is a strong predictor of academic success in school children. Memory impairments have been identified in HIV-I children, particularly in visuospatial processing. Verbal working memory has not been commonly investigated in this population, while it is unknown how the working memory profiles of HIV-EU children compare to their HIV-I and HIV-UU peers. Of interest was whether the working memory profiles of the HIV-EU children would be more similar to the HIV-I group or to the uninfected control group. The results revealed no significant differences in working memory performance between the HIV-I and HIV-EU groups. However, this does not mean that the etiology of the working memory deficits is the same in the two groups, as these groups showed important differences when compared to the control group. In comparison to the controls, the HIV-I group experienced difficulties with processing tasks irrespective of whether they drew on a verbal or visuospatial modality. This appears to stem from a generalized executive function deficit that also interferes with working memory. In the HIV-EU group, difficulties occurred with verbally based tasks, irrespective of whether they required storage or processing. For this group, the dual demands of complex processing and using a second language seem to result in demand exceeding capacity on verbal tasks. Both groups experienced the greatest difficulties with verbal processing tasks for these different reasons. Thus, disruption of different cognitive abilities could result in similar working memory profiles, as evidenced in this

  3. Working Memory Profiles in HIV-Exposed, Uninfected and HIV-Infected Children: A Comparison with Neurotypical Controls.

    Science.gov (United States)

    Milligan, Robyn; Cockcroft, Kate

    2017-01-01

    This study compared the working memory profiles of three groups of children, namely HIV-infected (HIV-I; n = 95), HIV-exposed, uninfected (HIV-EU; n = 86) and an HIV-unexposed, uninfected, (HIV-UU; n = 92) neurotypical control group. Working memory, an executive function, plays an important role in frontal lobe-controlled behaviors, such as motivation, planning, decision making, and social interaction, and is a strong predictor of academic success in school children. Memory impairments have been identified in HIV-I children, particularly in visuospatial processing. Verbal working memory has not been commonly investigated in this population, while it is unknown how the working memory profiles of HIV-EU children compare to their HIV-I and HIV-UU peers. Of interest was whether the working memory profiles of the HIV-EU children would be more similar to the HIV-I group or to the uninfected control group. The results revealed no significant differences in working memory performance between the HIV-I and HIV-EU groups. However, this does not mean that the etiology of the working memory deficits is the same in the two groups, as these groups showed important differences when compared to the control group. In comparison to the controls, the HIV-I group experienced difficulties with processing tasks irrespective of whether they drew on a verbal or visuospatial modality. This appears to stem from a generalized executive function deficit that also interferes with working memory. In the HIV-EU group, difficulties occurred with verbally based tasks, irrespective of whether they required storage or processing. For this group, the dual demands of complex processing and using a second language seem to result in demand exceeding capacity on verbal tasks. Both groups experienced the greatest difficulties with verbal processing tasks for these different reasons. Thus, disruption of different cognitive abilities could result in similar working memory profiles, as evidenced in this

  4. Working Memory Profiles in HIV-Exposed, Uninfected and HIV-Infected Children: A Comparison with Neurotypical Controls

    Directory of Open Access Journals (Sweden)

    Robyn Milligan

    2017-07-01

    Full Text Available This study compared the working memory profiles of three groups of children, namely HIV-infected (HIV-I; n = 95, HIV-exposed, uninfected (HIV-EU; n = 86 and an HIV-unexposed, uninfected, (HIV-UU; n = 92 neurotypical control group. Working memory, an executive function, plays an important role in frontal lobe-controlled behaviors, such as motivation, planning, decision making, and social interaction, and is a strong predictor of academic success in school children. Memory impairments have been identified in HIV-I children, particularly in visuospatial processing. Verbal working memory has not been commonly investigated in this population, while it is unknown how the working memory profiles of HIV-EU children compare to their HIV-I and HIV-UU peers. Of interest was whether the working memory profiles of the HIV-EU children would be more similar to the HIV-I group or to the uninfected control group. The results revealed no significant differences in working memory performance between the HIV-I and HIV-EU groups. However, this does not mean that the etiology of the working memory deficits is the same in the two groups, as these groups showed important differences when compared to the control group. In comparison to the controls, the HIV-I group experienced difficulties with processing tasks irrespective of whether they drew on a verbal or visuospatial modality. This appears to stem from a generalized executive function deficit that also interferes with working memory. In the HIV-EU group, difficulties occurred with verbally based tasks, irrespective of whether they required storage or processing. For this group, the dual demands of complex processing and using a second language seem to result in demand exceeding capacity on verbal tasks. Both groups experienced the greatest difficulties with verbal processing tasks for these different reasons. Thus, disruption of different cognitive abilities could result in similar working memory profiles, as

  5. CROI 2016: Hot Spots in HIV Infection and Advances in HIV Prevention.

    Science.gov (United States)

    Buchbinder, Susan P; Liu, Albert Y

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections (CROI) highlighted hot spots in HIV infection. Men who have sex with men (MSM), transgender populations, people who inject drugs, fisherfolk, migrants, adolescents, and older adults are heavily impacted in a number of regions. Stigma contributes to risk behaviors and HIV acquisition across populations. HIV testing is a crucial first step in the HIV care continuum, and several large community-based surveys are underway in Africa to increase HIV testing, linkage to care, and uptake of antiretroviral treatment. Advances in preexposure prophylaxis (PrEP) featured prominently at CROI 2016. Two large efficacy trials of a vaginal ring containing the investigational drug dapivirine demonstrated efficacy and safety in preventing HIV infections in women in Africa. Data on the safety of long-acting injectable PrEP and several investigational PrEP drugs and formulations were also presented. Knowledge and use of PrEP among MSM in the United States appears to be increasing, and high uptake was seen among black MSM when provided as part of a culturally tailored support program. The use of broadly neutralizing antibodies for HIV prevention is a novel and promising approach to be evaluated in efficacy trials.

  6. Placental pathology in HIV infection at term: a comparison with HIV-uninfected women.

    Science.gov (United States)

    Kalk, Emma; Schubert, Pawel; Bettinger, Julie A; Cotton, Mark F; Esser, Monika; Slogrove, Amy; Wright, Colleen A

    2017-05-01

    To describe and correlate placental characteristics from pregnancies in HIV-infected and HIV-negative women with maternal and infant clinical and immunological data. Prospective descriptive study of placentas from term, uncomplicated vaginal births in a cohort of HIV-infected (n = 120) and HIV-negative (n = 103) women in Cape Town, South Africa. Microscopic and macroscopic features were used to determine pathological cluster diagnoses. The majority of HIV-infected women received some form of drug treatment for the prevention of vertical transmission of HIV. Data were analysed using logistic regression. HIV-infected women were older (median [IQR] 27.4 years [24-31] vs. 25.8 [23-30]), more likely to be multiparous (81.7% vs. 71.8%) and had lower CD4 counts (median [IQR] 323.5 cells/ml [235-442] vs. 467 [370-656]). There were no differences in gestational age at first antenatal visit or at delivery. The proportion of specimens with placental lesions was similar in both groups (39.2% vs. 44.7%). Half of all samples were below the tenth percentile expected-weight-for-gestation regardless of HIV status. This was unaffected by adjustment for confounding variables. Maternal vascular malperfusion (MVM) was more frequent in HIV infection (24.2% vs. 12.6%; P = 0.028), an association which strengthened after adjustment (aOR 2.90 [95% confidence interval 1.11-7.57]). Otherwise the frequency of individual diagnoses did not differ between the groups on multivariate analysis. In this cohort of term, uncomplicated pregnant women, few differences were observed between the HIV-infected and uninfected groups apart from MVM. This lesion may underlie the development of hypertensive disorders of pregnancy, which have been observed at higher rates in some HIV-infected women on ART. © 2017 John Wiley & Sons Ltd.

  7. [Impact of HIV/HBV infection and HIV/HBV co-infection on outcomes of pregnancy].

    Science.gov (United States)

    Yang, Y; Cheng, W T; Zhou, Y B; Jiang, Q W

    2017-06-10

    Both HIV and HBV infection have become major health problems, of global concern, due to the high prevalence in the past few decades. Data from cumulated epidemiological surveys have shown the links between maternal HIV or HBV infection and adverse outcomes on pregnancy. Maternal HIV or HBV infection may also increase the mother-to-child (MTCT) transmission of the two diseases. However, association between HIV-HBV co-infection and adverse pregnancy is still inconclusive. Does maternal HIV-HBV co-infection have an impact on mother-to-child transmission on either HIV or HBV? Study on effective precautionary measures to promote both maternal and child's health is deemed necessary.

  8. Factors Associated with Recent HIV Testing among Heterosexuals at High-Risk for HIV Infection in New York City

    Directory of Open Access Journals (Sweden)

    Marya eGwadz

    2016-04-01

    Full Text Available Background. The CDC recommends persons at high-risk for HIV infection in the United States receive annual HIV testing to foster early HIV diagnosis and timely linkage to health care. Heterosexuals make up a significant proportion of incident HIV infections (>25%, but test for HIV less frequently than those in other risk categories. Yet factors that promote or impede annual HIV testing among heterosexuals are poorly understood. The present study examines individual/attitudinal-, social-, and structural-level factors associated with past-year HIV testing among heterosexuals at high-risk for HIV. Methods. Participants were African American/Black and Hispanic heterosexual adults (N=2307 residing in an urban area with both high poverty and HIV prevalence rates. Participants were recruited by respondent-driven sampling (RDS in 2012-2015 and completed a computerized structured assessment battery covering background factors, multi-level putative facilitators of HIV testing, and HIV testing history. Separate logistic regression analysis for males and females identified factors associated with past-year HIV testing.Results. Participants were mostly male (58%, African American/Black (75%, and 39 years old on average (SD = 12.06 years. Lifetime homelessness (54% and incarceration (62% were common. Half reported past-year HIV testing (50% and 37% engaged in regular, annual HIV testing. Facilitators of HIV testing common to both genders included sexually transmitted infection (STI testing or STI diagnosis, peer norms supporting HIV testing, and HIV testing access. Among women, access to general medical care and extreme poverty further predicted HIV testing, while recent drug use reduced the odds of past-year HIV testing. Among men, past-year HIV testing was also associated with lifetime incarceration and substance use treatment.Conclusions. The present study identified gaps in rates of HIV testing among heterosexuals at high-risk for HIV, and both common and

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that ... AIDS) are often linked and referred to as "HIV/AIDS." HIV can be transferred between people if an ...

  10. Living with HIV/AIDS

    Science.gov (United States)

    ... destroying the white blood cells that fight infection. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. Infection with HIV is serious. But thanks to ...

  11. HIV-positive patients’ and their families’ comprehension of HIV- and AIDS-related information

    Directory of Open Access Journals (Sweden)

    Gedina E. de Wet

    2013-04-01

    Full Text Available Despite acknowledgement of the importance of sharing HIV- and AIDS-related information with people living with HIV, it is still unclear as to what their actual comprehension is of this information. This research was part of a larger project, Tswaragano, conducted in the North-West Province, South Africa, which explored and described the competence, ability and strengths of the family of the HIV-positive patient during home support. This research focused on Potchefstroom in the North-West Province. This article focuses on research with the objective being to explore and describe the comprehension of HIV-positive patients and their families with regard to HIV- and AIDS-related information, and to formulate recommendations to improve their comprehension of this information. A quantitative, explorative and descriptive survey design was followed. Data were collected by means of questionnaires completed by HIV-positive patients (n = 79 and their family members (n = 34. Descriptive statistical analysis by means of frequency analysis was conducted. Ethical considerations and mechanisms to enhance validity and reliability are discussed. The results indicated that both HIV-positive respondents and their families face social and financial challenges due to unemployment and low income. A strength found in this research is that the majority of respondents are linked to a church, which can be a valuable platform to share information on HIV and AIDS. With regards to sharing, sources and comprehension of HIV- and AIDS-related information, it is apparent that respondents perceived that pre- and post-counselling provided an opportunity for information sharing, but that they need health care workers to spend more time with them, to be non-judgemental and to make more use of visual aids. It furthermore seems that the majority of HIV-positive respondents in this study did comprehend the need for and negotiate for safer sexual practices. It was concluded that

  12. HIV-positive patients’ and their families’ comprehension of HIV- and AIDS-related information

    Directory of Open Access Journals (Sweden)

    Gedina E. de Wet

    2013-04-01

    Full Text Available Despite acknowledgement of the importance of sharing HIV- and AIDS-related information with people living with HIV, it is still unclear as to what their actual comprehension is of this information. This research was part of a larger project, Tswaragano, conducted in the North-West Province, South Africa, which explored and described the competence, ability and strengths of the family of the HIV-positive patient during home support. This research focused on Potchefstroom in the North-West Province. This article focuses on research with the objective being to explore and describe the comprehension of HIV-positive patients and their families with regard to HIV- and AIDS-related information, and to formulate recommendations to improve their comprehension of this information. A quantitative, explorative and descriptive survey design was followed. Data were collected by means of questionnaires completed by HIV-positive patients (n= 79 and their family members (n= 34. Descriptive statistical analysis by means of frequency analysis was conducted. Ethical considerations and mechanisms to enhance validity and reliability are discussed. The results indicated that both HIV-positive respondents and their families face social and financial challenges due to unemployment and low income. A strength found in this research is that the majority of respondents are linked to a church, which can be a valuable platform to share information on HIV and AIDS. With regards to sharing, sources and comprehension of HIV- and AIDS-related information, it is apparent that respondents perceived that pre- and post-counselling provided an opportunity for information sharing, but that they need health care workers to spend more time with them, to be non-judgemental and to make more use of visual aids. It furthermore seems that the majority of HIV-positive respondents in this study did comprehend the need for and negotiate for safer sexual practices. It was concluded that although

  13. HIV p24 as scaffold for presenting conformational HIV Env antigens.

    Directory of Open Access Journals (Sweden)

    Maria Tagliamonte

    Full Text Available Heterologous protein scaffolds engrafted with structurally defined HIV Env epitopes recognized by broadly neutralizing monoclonal antibodies (MAbs represent a promising strategy to elicit broad neutralizing antibodies. In such regards, a protein scaffold based on the HIV p24 CA protein is a highly attractive approach, providing also Gag epitopes for eliciting HIV non-neutralizing protective antibodies and specific CD4(+ and CD8(+ T cell responses. In the present study, computational techniques were employed to verify the presence of acceptor sites for conformational HIV Env epitopes and, as proof of concept, the analysis of HIV p24 CA-based scaffolds using a complete V3 loop in a MAb-bound conformation is presented. The V3-p24 epitope-scaffold proteins show the formation of capsomers made of hexamers similarly to the p24 wild type protein. Moreover, the conformational V3 loop presented on p24 scaffold is recognized by a panel of anti-V3 MAbs. The results suggest that HIV p24 CA protein has suitable acceptor sites for engrafting foreign epitopes, without disrupting the formation of capsomer hexamer structures, and that the V3 epitope does retain its antibody-bound conformation. This strongly support the feasibility of developing a scaffolding strategy based on p24 CA proteins displaying conformational minimal structural, antigenic HIV Env epitopes.

  14. Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV Control.

    Directory of Open Access Journals (Sweden)

    Margaret E Ackerman

    2016-01-01

    Full Text Available Elite controllers (ECs represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune-recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure.

  15. HIV infection in the elderly

    Directory of Open Access Journals (Sweden)

    Nancy Nguyen

    2008-09-01

    Full Text Available Nancy Nguyen1, Mark Holodniy21University of the Pacific School of Pharmacy and Health Sciences, Stockton, CA, USA; 2VA Palo Alto Health Care System, Palo Alto, CA, USAAbstract: In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evolved from an acute disease process to being managed as a chronic medical condition. As treated HIV-infected patients live longer and the number of new HIV diagnoses in older patients rise, clinicians need to be aware of these trends and become familiar with the management of HIV infection in the older patient. This article is intended for the general clinician, including geriatricians, and will review epidemiologic data and HIV treatment as well as provide a discussion on medical management issues affecting the older HIV-infected patient.Keywords: HIV, epidemiology, treatment, aging, review

  16. HIV Stigma: Perspectives from Kenyan Child Caregivers and Adolescents Living with HIV

    Science.gov (United States)

    McHenry, Megan Song; Nyandiko, Winstone M.; Scanlon, Michael L.; Fischer, Lydia J.; McAteer, Carole I.; Aluoch, Josephine; Naanyu, Violet; Vreeman, Rachel C.

    2017-01-01

    Stigma shapes all aspects of HIV prevention and treatment, yet there are limited data on how HIV-infected youth and their families are affected by stigma in sub-Saharan Africa. The authors conducted a qualitative study using focus group discussions among 39 HIV-infected adolescents receiving care at HIV clinics in western Kenya and 53 caregivers of HIV-infected children. Participants felt that while knowledge and access to treatment were increasing, many community members still held negative and inaccurate views about HIV, including associating it with immorality and believing in transmission by casual interactions. Stigma was closely related to a loss of social and economic support but also included internalized negative feelings about oneself. Participants identified treatment-related impacts of stigma, including nonadherence, nondisclosure of status to child or others, and increased mental health problems. Qualitative inquiry also provided insights into how to measure and reduce stigma among affected individuals and families. PMID:27655835

  17. HIV Stigma: Perspectives from Kenyan Child Caregivers and Adolescents Living with HIV.

    Science.gov (United States)

    McHenry, Megan Song; Nyandiko, Winstone M; Scanlon, Michael L; Fischer, Lydia J; McAteer, Carole I; Aluoch, Josephine; Naanyu, Violet; Vreeman, Rachel C

    Stigma shapes all aspects of HIV prevention and treatment, yet there are limited data on how HIV-infected youth and their families are affected by stigma in sub-Saharan Africa. The authors conducted a qualitative study using focus group discussions among 39 HIV-infected adolescents receiving care at HIV clinics in western Kenya and 53 caregivers of HIV-infected children. Participants felt that while knowledge and access to treatment were increasing, many community members still held negative and inaccurate views about HIV, including associating it with immorality and believing in transmission by casual interactions. Stigma was closely related to a loss of social and economic support but also included internalized negative feelings about oneself. Participants identified treatment-related impacts of stigma, including nonadherence, nondisclosure of status to child or others, and increased mental health problems. Qualitative inquiry also provided insights into how to measure and reduce stigma among affected individuals and families.

  18. HIV and mycobacteria.

    Science.gov (United States)

    Procop, Gary W

    2017-07-01

    The importance of mycobacteria as opportunistic pathogens, particularly members of the M. avium complex (MAC), in patients with progressive HIV infection was recognized early in the AIDS epidemic. It took longer to appreciate the global impact and devastation that would result from the deadly synergy that exists between HIV and M. tuberculosis. This HIV/M. tuberculosis co-pandemic is ongoing and claiming millions of lives every year. In addition to MAC, a number of other non-tuberculous mycobacteria have been recognized as opportunistic pathogens in HIV-infected individuals; some of these are more commonly encountered (e.g., M. kansasii) than others (M. haemophilum and M. genevense). Finally, there are challenges to concomitantly treating the HIV and the infecting Mycobacterium species, because of antimicrobial resistance, therapeutic side-effects and the complex pharmacologic interactions of the antiretroviral and antimycobacterial multidrug therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. ORIGINAL ARTICLES HIV prevention responsibilities in HIV vaccine ...

    African Journals Online (AJOL)

    HIV/AIDS Vaccines Ethics Group (HAVEG), School of Psychology, University of. KwaZulu-Natal ... receive access to risk reduction counselling on safer sex, education .... debate regarding how to proceed should acyclovir have shown to decrease HIV ... or a single pivotal trial (phase III trial) that provides as much evidence of ...

  20. How you get HIV/AIDS

    Science.gov (United States)

    How you get HIV/AIDS Which body fluids contain HIV? HIV is a virus that lives in blood and other fluids in the body. Moving ... answers to any questions you have about HIV/AIDS. Your public health department and health care provider ...

  1. HIV/AIDS in Women - Multiple Languages

    Science.gov (United States)

    ... medicines and women - HIV medicines, part 7 - English MP3 HIV medicines and women - HIV medicines, part 7 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 HIV medicines and women - HIV medicines, part 7 - ...

  2. Profile of the HIV epidemic in Cape Verde: molecular epidemiology and drug resistance mutations among HIV-1 and HIV-2 infected patients from distinct islands of the archipelago.

    Science.gov (United States)

    de Pina-Araujo, Isabel Inês M; Guimarães, Monick L; Bello, Gonzalo; Vicente, Ana Carolina P; Morgado, Mariza G

    2014-01-01

    HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010-2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1-75) and 47 (IQR = 12-84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be implemented.

  3. Nutrition and HIV-Positive Pregnancy

    Science.gov (United States)

    Montgomery, Kristen S.

    2003-01-01

    When an HIV-positive woman becomes pregnant, additional nutritional considerations are warranted. Compared to routine prenatal nutritional assessment and intervention, pregnant HIV-positive women have increased needs to promote a healthy outcome. This column contains information on HIV and pregnancy, nutrition and infection, and nutrition for HIV-positive pregnancy. This content can be integrated into childbirth education settings to improve care to women who are HIV-positive. PMID:17273329

  4. Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

    Directory of Open Access Journals (Sweden)

    V. B. Musatov

    2015-01-01

    Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central

  5. Adductor Canal Block versus Femoral Nerve Block and Quadriceps Strength

    DEFF Research Database (Denmark)

    Jæger, Pia Therese; Nielsen, Zbigniew Jerzy Koscielniak; Henningsen, Lene Marianne

    2013-01-01

    : The authors hypothesized that the adductor canal block (ACB), a predominant sensory blockade, reduces quadriceps strength compared with placebo (primary endpoint, area under the curve, 0.5-6 h), but less than the femoral nerve block (FNB; secondary endpoint). Other secondary endpoints were...

  6. Examining anxiety sensitivity as an explanatory construct underlying HIV-related stigma: Relations to anxious arousal, social anxiety, and HIV symptoms among persons living with HIV.

    Science.gov (United States)

    Brandt, Charles P; Paulus, Daniel J; Jardin, Charles; Heggeness, Luke; Lemaire, Chad; Zvolensky, Michael J

    2017-05-01

    Persons living with HIV (PLHIV) are a health disparity subgroup of the overall population for mental and physical health problems. HIV-related stigma has been shown to increase anxiety symptoms and HIV symptoms among PLHIV. However, little is known about factors that may impact the relations between HIV-related stigma and anxiety symptoms and HIV symptoms among PLHIV. To address this gap in the literature, the current study examined anxiety sensitivity (i.e., the extent to which individuals believe anxiety and anxiety-related sensations) in the relation between HIV-related stigma, social anxiety, anxious arousal, and HIV symptoms among a sample of 87 PLHIV (60.9% cis gender male, 52.9% Black, non-Hispanic). Results indicated that anxiety sensitivity mediated the relations between HIV-related stigma and the dependent variables, with effect sizes indicating moderate to large effects of anxiety sensitivity on these relations. Findings suggest that anxiety sensitivity be a mechanistic factor in the relations between HIV-related stigma and social anxiety, anxious arousal, and HIV symptoms, and therefore, be important element in efforts to reduce mental/physical health disparity among this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Trichomoniasis and HIV interactions: a review

    Science.gov (United States)

    Kissinger, Patricia; Adamski, Alys

    2013-01-01

    Objective To discuss the epidemiology of Trichomonas vaginalis (TV) and HIV co-infections, the role of TV in acquisition and transmission of HIV, special treatment considerations for TV among women with HIV and the prevention of TV among HIV-infected persons. Design Systematic review. Data source Review of literature of EMBASE and PubMed databases from January 1990 to February 2013. Search keywords included TV, HIV co-infections, HIV acquisition, HIV transmission, HIV shedding, TV treatment, HIV and couples studies. Review method We included studies of any design that contained the selected search words and were published during the specified time frame. We then searched the reference lists of included papers for additional papers and included these when relevant. Results There is strong evidence that TV increases both transmission and acquisition of HIV among women, and that successful treatment for TV can reduce HIV genital shedding. Single dose metronidazole (MTZ) should no longer be used for HIV+ women with TV given the high rates of asymptomatic bacterial vaginosis co-infections and other factors that may render MTZ less effective in HIV+ women. Prevention of TV among HIV+ persons is similar to among HIV, including promotion of condoms as well as regular screening and prompt treatment. There may be a role for expedited partner treatment for the prevention of repeat infections, but most repeat infections are clinical treatment failures. Diligence in screening and treating TV among both HIV− susceptible and HIV+ persons is an important public health strategy. PMID:23605851

  8. Kebijakan Pengendalian HIV/AIDS di Denpasar

    Directory of Open Access Journals (Sweden)

    Tri Rini Puji Lestari

    2013-08-01

    Full Text Available Secara nasional, Indonesia telah mengantisipasi epidemi HIV/AIDS, tetapi jumlah kasus HIV/AIDS di Provinsi Bali dari tahun ke tahun memperlihatkan peningkatan yang semakin mengkhawatirkan. Penelitian ini bertujuan untuk mengetahui perkembangan jumlah kasus dan kebijakan penanggulangan HIV/AIDS di Denpasar. Penelitian ini menggunakan metode kualitatif yang dilakukan di Denpasar pada tanggal 11-17 September 2011. Sampel penelitian ini menggunakan informan terpilih yaitu kepala bappeda, pejabat Dinas Kesehatan Kabupaten Denpasar, direktur rumah sakit, puskesmas, ketua komisi penanggulangan AIDS di kabupaten/kota dan pemerhati HIV/AIDS termasuk ODHA. Penelitian menemukan jumlah kasus HIV/AIDS di Kota Denpasar yang tertinggi dan penularan terbesarnya melalui hubungan seks. Namun, dukungan pemerintah daerah dalam upaya pencegahan dan penanggulangan HIV/AIDS terlihat belum maksimal. Padahal kebijakan penanggulangan HIV/AIDS sangat ditentukan oleh cara pandang pemerintah terhadap penyakit HIV/AIDS. Untuk itu, perlu peningkatan pemahaman tentang HIV/AIDS serta pencegahan dan penanganan semua pihak terkait sehingga penanggulangan HIV/AIDS dapat lebih efektif, efisien, dan tepat sasaran. Nationally, Indonesia anticipated HIV/AIDS epidemic, but the number of cases of HIV/AIDS in Bali province from year to year showed an increase in the increasingly alarming. This study aimed to determine the number of cases and the development of policies on HIV / AIDS in Denpasar. This research was conducted using qualitative methods in Denpasar on 11-17 September 2011. The study sample was selected using the informant is head of planning, Denpasar District health officers, the director of the hospital, health center, chairman of the commission on AIDS in the district/city and observer of HIV / AIDS, including people living with HIV. The study found the number of cases of HIV / AIDS in the city of Denpasar is the highest and greatest transmission through sexual intercourse

  9. Asymmetric PS-block-(PS-co-PB)-block-PS block copolymers: morphology formation and deformation behaviour

    International Nuclear Information System (INIS)

    Adhikari, Rameshwar; Huy, Trinh An; Buschnakowski, Matthias; Michler, Goerg H; Knoll, Konrad

    2004-01-01

    Morphology formation and deformation behaviour of asymmetric styrene/butadiene triblock copolymers (total polystyrene (PS) content ∼70%) consisting of PS outer blocks held apart by a styrene-co-butadiene random copolymer block (PS-co-PB) each were investigated. The techniques used were differential scanning calorimetry, transmission electron microscopy, uniaxial tensile testing and Fourier-transform infrared spectroscopy. A significant shift of the phase behaviour relative to that of a neat symmetric triblock copolymer was observed, which can be attributed to the asymmetric architecture and the presence of PS-co-PB as a soft block. The mechanical properties and the microdeformation phenomena were mainly controlled by the nature of their solid-state morphology. Independent of morphology type, the soft phase was found to deform to a significantly higher degree of orientation when compared with the hard phase

  10. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    Science.gov (United States)

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-09-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tests (INNO-LIA HIV-I/II Score) and NEW LAV BLOT II (Bio-Rad). Four hundred and forty three sequential stored HIV-positive serum samples, of known HIV-type, were evaluated. Genie II HIV1/HIV2, Immunoflow HIV1-HIV2 and SD Bioline HIV 1/2 3.0 had 100% sensitivity (95% CI, 98.9-100%) while for First Response HIV Card Test 1-2.0 this was 99.5% (95% CI, 98.2%-99.9%). In terms of discriminatory capacity, Genie II HIV1/HIV2 identified 382/ 384(99.5%) HIV-1 samples, 49/ 52(95%) HIV-2 and 7/7(100%) HIV-positive untypable samples. Immunoflow HIV1-HIV2 identified 99% HIV-1, 67% HIV-2 and all HIV-positive untypable samples. First Response HIV Card Test 1-2.0 identified 94% HIV-1, 64% HIV-2 and 57% HIV-positive untypable samples. SD-Bioline HIV 1/2 3.0 was the worst overall performer identifying 65% HIV-1, 69% HIV-2 and all HIV-positive untypable samples. The use of SD Bioline HIV 1/2 3.0 (the current standard in Guinea-Conakry) as a discriminatory HIV test is poor and may be best replaced by Immunoflow HIV1-HIV2. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  11. University students and HIV in Namibia: an HIV prevalence survey and a knowledge and attitude survey.

    Science.gov (United States)

    de Beer, Ingrid H; Gelderblom, Huub C; Schellekens, Onno; Gaeb, Esegiel; van Rooy, Gert; McNally, Alta; Wit, Ferdinand W; Tobias, Rinke de Wit F

    2012-02-22

    With an overall adult HIV prevalence of 15.3%, Namibia is facing one of the largest HIV epidemics in Africa. Young people aged 20 to 34 years constitute one of the groups at highest risk of HIV infection in Namibia. However, little is known about the impact of HIV on this group and its access to healthcare. The purpose of this study was to estimate HIV prevalence, to assess the knowledge of and attitudes towards HIV/AIDS, and to assess access to healthcare among university students in Namibia. We assessed HIV/AIDS knowledge and attitudes, HIV prevalence and access to healthcare among students at the Polytechnic of Namibia and the University of Namibia. HIV prevalence was tested through anonymous oral fluid-based tests. Half (n = 2790/5568) of the university students and 45% (n = 2807/6302) of the Polytechnic students participated in the knowledge and attitudes surveys. HIV/AIDS knowledge was reasonable, except for misperceptions about transmission. Awareness of one's own HIV status and risks was low. In all, 55% (n = 3055/5568) of university students and 58% (n = 3680/6302) of Polytechnic students participated in the HIV prevalence survey; 54 (1.8%) university students and 103 (2.8%) Polytechnic students tested HIV positive. Campus clinics were not the major providers of healthcare to the students. Meaningful strategies addressing the gap between knowledge, attitude and young people's perception of risk of HIV acquisition should be implemented. HIV prevalence among Namibian university students appears relatively low. Voluntary counselling and testing should be stimulated. Efforts should be made to increase access to healthcare through the campus clinics.

  12. ANALYSIS OF HIV SUBTYPES AND CLINICAL STAGING OF HIV DISEASE/AIDS IN EAST JAVA

    Directory of Open Access Journals (Sweden)

    Yulia Ismail

    2012-04-01

    Full Text Available Human Immunodeficiency Virus type 1 (HIV-1 known to cause Acquired Immune Deficiency Syndrome (AIDS disease are divided into several subtypes (A, B, C, D, F, G, H, J, K and Circulating Recombinant Form (CRF. Different characteristics of subtype of the virus and its interaction with the host can affect the severity of the disease. This study was to analyze HIV-1 subtypes circulating in HIV/AIDS patients from the East Java region descriptively and to analyze its relationship with clinical stadiums of HIV/AIDS. Information from this research was expected to complement the data of mocular epidemiology of HIV in Indonesia. This study utilited blood plasma from patients who had been tested to be HIV positive who sected treatment to or were reffered to the Intermediate Care Unit of Infectious Disease (UPIPI Dr. Soetomo Hospital Surabaya from various area representing the East Java regions. Plasma was separated from blood samples by centrifugation for use in the the molecular biology examination including RNA extraction, nested PCR using specific primer for HIV gp120 env gene region, DNA purifying, DNA sequencing, and homology and phylogenetic analysis. Based on the nucleotide sequence of the HIV gp120 env gene, it was found that the most dominant subtypes in East Java were in one group of Circulating Recombinant Form (CRF that is CRF01_AE, CRF33_01B and CRF34_01B which was also found in Southeast Asia. In the phylogenetic tree, most of HIV samples (30 samples are in the same branch with CRF01_AE, CRF33_01B and CRF34_01B, except for one sample (HIV40 which is in the same branch with subtype B. HIV subtypes are associated with clinical stadiums (disease severity since samples from different stages of HIV disease have the same subtype.

  13. HIV-Related Cognitive Impairment of Orphans in Myanmar With Vertically Transmitted HIV Taking Antiretroviral Therapy.

    Science.gov (United States)

    Linn, Kyaw; Fay, Alexander; Meddles, Katherine; Isbell, Sara; Lin, Phyo Nay; Thair, Cho; Heaps, Jodi; Paul, Robert; Mar, Soe Soe

    2015-12-01

    We determined the effect of perinatally acquired HIV on neurocognition in Myanmar children treated with antiretroviral therapy by comparison to demographically matched seronegative children. Myanmar has one of the highest HIV-1 prevalence rates in Southeast Asia. Studies from other resource-poor countries have shown that HIV-infected children differ in socioeconomic, nutritional and caregiver status compared to normal controls. Some vertically infected orphans in Myanmar reside separately from HIV-uninfected children in separate orphanages, thus the demographic variables of interest are naturally controlled. This study provides a unique evaluation of the neurocognitive effects of HIV in children, with control over key demographic variables. We hypothesized that HIV-infected orphans would perform significantly worse on cognitive indices compared with HIV-negative orphans. A battery of cognitive tests sensitive to HIV-associated impairments in children was administered to 28 perinatally acquired HIV-positive children and 31 HIV-negative children from two orphanages in Myanmar; 21 children from each cohort underwent testing at baseline and again after 12 months. Baseline comparison of the two groups indicated that the HIV-infected children performed poorly across all tests, with significant group differences in executive function, visuospatial reasoning, fine motor dexterity, and visual motor integration. On subsequent testing, both cohorts of children showed improvements across multiple domains, with no significant effect of age at treatment initiation. Our results demonstrate a strong effect of HIV infection on specific neurocognitive deficits in vertically infected children. Understanding viral and host determinants and timing and choice of antiretroviral therapy on cognition will be critical to preventing cognitive impairment of children with HIV. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Osteopenia and osteoporosis in people living with HIV: multiprofessional approach

    Directory of Open Access Journals (Sweden)

    Lima AL

    2011-12-01

    Full Text Available Ana Lucia Lei Munhoz Lima, Priscila Rosalba D de Oliveira, Perola Grimberg Plapler, Flora Maria D Andrea Marcolino, Eduardo de Souza Meirelles, André Sugawara, Riccardo Gomes Gobbi, Alexandre Leme Godoy dos Santos , Gilberto Luis CamanhoInstitute of Orthopedics and Traumatology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, BrazilAbstract: Increasing bone mineralization abnormalities observed among people living with HIV (PLWHIV result from various factors relating to the host, the virus, and the antiretrovirals used. Today, HIV infection is considered to be a risk factor for bone mineralization disorders. The test most recommended for diagnosing osteoporosis is measurement of bone mineral density by means of dual energy X-ray absorptiometry at two sites. Osteoporosis treatment has the aims of bone mass improvement and fracture control. A combination of calcium and vitamin D supplementation may reduce the risk of fractures. Antiresorptive drugs act by blocking osteoclastic activity and reducing bone remodeling. On the other hand, bone-forming drugs stimulate osteoblastogenesis, thereby stimulating the formation of bone matrix. Mixed-action medications are those that are capable of both stimulating bone formation and inhibiting reabsorption. Antiresorptive drugs form the group of medications with the greatest quantity of scientific evidence confirming their efficacy in osteoporosis treatment. Physical activity is a health promotion strategy for the general population, but only preliminary data on its real value and benefit among PLWHIV are available, especially in relation to osteoporosis.Keywords: osteoporosis, HIV/AIDS, diagnosis, treatment, exercise

  15. Effectiveness and cost of treatment with maraviroc in HIV infection

    Directory of Open Access Journals (Sweden)

    Viola Sacchi

    2009-12-01

    Full Text Available Since 1995, life expectancy and quality of life of HIV patients improved significantly due to the use of Highly Active Anti-Retroviral Therapy (HAART, consisting of different combinations of three classes of antiretroviral agents, nucleoside and non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. Recently, new treatment options for individuals developing resistance to these drugs have become available, with the appearance of new drug classes like integrase inhibitors, fusion inhibitors and CCR5 antagonists. Maraviroc is the first antiretroviral agent belonging to the latter drug class approved for clinical use. CCR5 receptor antagonists act by blocking the interaction of the HIV virus with the CCR5 chemokine receptor, a co-receptor essential to the entry process of R5-tropic viruses. The drug is indicated, in combination with other antiretroviral products, for treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable virus strains. Results of main phase III clinical trials indicate that maraviroc, in combination with optimized background therapy (OBT, causes significantly greater reductions in viral load and increases in CD4+ cell count, as compared to OBT alone in this kind of patients. In Italy, the monthly cost of maraviroc therapy is about € 780. A number of economic evaluations, performed for different settings, demonstrate that the therapy including maraviroc is cost-effective if compared to OBT alone, determining an ICER generally below the threshold of three times the GDP per capita. In the Italian context, the ICER determined by OBT + maraviroc vs OBT alone is approximately 45,000 €/LYG.

  16. Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2011-07-01

    Full Text Available Abstract Background Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively. However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i to assemble and construct zinc finger arrays and nucleases (ZFN with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii to advance a model for pre-clinically testing lentiviral vectors (LV that deliver and transduce either ZFN genotype. Methods and Results First, we computationally generated the consensus sequences of (a 114 dsDNA-binding zinc finger (Zif arrays (ZFAs or ZifHIV-pol and (b two zinc-finger nucleases (ZFNs which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN. Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN. Second, a model for constructing lentiviral vectors (LVs that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively is proposed. Third, two preclinical models for controlled testing of

  17. Proviral HIV-genome-wide and pol-gene specific zinc finger nucleases: usability for targeted HIV gene therapy.

    Science.gov (United States)

    Wayengera, Misaki

    2011-07-22

    Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases) AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively). However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX) at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i) to assemble and construct zinc finger arrays and nucleases (ZFN) with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii) to advance a model for pre-clinically testing lentiviral vectors (LV) that deliver and transduce either ZFN genotype. First, we computationally generated the consensus sequences of (a) 114 dsDNA-binding zinc finger (Zif) arrays (ZFAs or ZifHIV-pol) and (b) two zinc-finger nucleases (ZFNs) which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN). Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN). Second, a model for constructing lentiviral vectors (LVs) that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively) is proposed. Third, two preclinical models for controlled testing of the safety and efficacy of either of these

  18. Adductor canal block versus femoral nerve block for analgesia after total knee arthroplasty

    DEFF Research Database (Denmark)

    Jaeger, Pia; Zaric, Dusanka; Fomsgaard, Jonna Storm

    2013-01-01

    Femoral nerve block (FNB), a commonly used postoperative pain treatment after total knee arthroplasty (TKA), reduces quadriceps muscle strength essential for mobilization. In contrast, adductor canal block (ACB) is predominately a sensory nerve block. We hypothesized that ACB preserves quadriceps...

  19. What Is HIV/AIDS?

    Science.gov (United States)

    ... take their HIV medications as directed, and different health-related choices they make, such as decisions to eat a healthful diet , exercise , and not smoke . Is There a Cure for HIV? No effective cure currently exists for HIV. But with proper ...

  20. Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users.

    Science.gov (United States)

    Amendola, A; Boschini, A; Colzani, D; Anselmi, G; Oltolina, A; Zucconi, R; Begnini, M; Besana, S; Tanzi, E; Zanetti, A R

    2001-12-01

    The immunogenicity of an anti-influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV-1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV-1-positive subjects was measured. HIV-1-positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV-1-negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV-1-positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (> or = 1:40) increased significantly after vaccination, especially in HIV-1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV-1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV-1. Copyright 2001 Wiley-Liss, Inc.

  1. Linkage to HIV care, postpartum depression, and HIV-related stigma in newly diagnosed pregnant women living with HIV in Kenya: a longitudinal observational study

    OpenAIRE

    Turan, Bulent; Stringer, Kristi L; Onono, Maricianah; Bukusi, Elizabeth A; Weiser, Sheri D; Cohen, Craig R; Turan, Janet M

    2014-01-01

    Background While studies have suggested that depression and HIV-related stigma may impede access to care, a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV. However, this has not been investigated in postpartum women living with HIV. Furthermore, linkage to care itself may have additional impacts on postpartum depression beyond the effect...

  2. Block That Pain!

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Block That Pain! Past Issues / Fall 2007 Table of ... contrast, most pain relievers used for surgical procedures block activity in all types of neurons. This can ...

  3. The role of enacted stigma in parental HIV disclosure among HIV-infected parents in China.

    Science.gov (United States)

    Qiao, Shan; Li, Xiaoming; Zhou, Yuejiao; Shen, Zhiyong; Tang, Zhenzhu; Stanton, Bonita

    2015-01-01

    Existing studies have delineated that HIV-infected parents face numerous challenges in disclosing their HIV infection to the children ("parental HIV disclosure"), and practices of parental HIV disclosure vary with individual characteristics, family contexts, and social environment. Using cross-sectional data from 1254 HIV-infected parents who had children aged 5-16 years in southwest China, the current study examined the association of parental HIV disclosure with mental health and medication adherence among parents and explored the possible effect of enacted stigma on such association. Multivariate analysis of variance revealed that parents who had experienced disclosure to children reported higher level enacted stigma, worse mental health conditions, and poorer medication adherence. Enacted stigma partially mediated the associations between disclosure and both mental health and medication adherence after controlling basic background characteristics. Our findings highlight the importance of providing appropriate disclosure-related training and counseling service among HIV-infected parents. In a social setting where HIV-related stigma is still persistent, disclosure intervention should address and reduce stigma and discrimination in the practice of parental HIV disclosure.

  4. Study of Structure-active Relationship for Inhibitors of HIV-1 Integrase LEDGF/p75 Interaction by Machine Learning Methods.

    Science.gov (United States)

    Li, Yang; Wu, Yanbin; Yan, Aixia

    2017-07-01

    HIV-1 integrase (IN) is a promising target for anti-AIDS therapy, and LEDGF/p75 is proved to enhance the HIV-1 integrase strand transfer activity in vitro. Blocking the interaction between IN and LEDGF/p75 is an effective way to inhibit HIV replication infection. In this work, 274 LEDGF/p75-IN inhibitors were collected as the dataset. Support Vector Machine (SVM), Decision Tree (DT), Function Tree (FT) and Random Forest (RF) were applied to build several computational models for predicting whether a compound is an active or weakly active LEDGF/p75-IN inhibitor. Each compound is represented by MACCS fingerprints and CORINA Symphony descriptors. The prediction accuracies for the test sets of all the models are over 70 %. The best model Model 3B built by FT obtained a prediction accuracy and a Matthews Correlation Coefficient (MCC) of 81.08 % and 0.62 on test set, respectively. We found that the hydrogen bond and hydrophobic interactions are important for the bioactivity of an inhibitor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Understanding HIV Transmission Risk Behavior Among HIV-Infected South Africans Receiving Antiretroviral Therapy: An Information—Motivation—Behavioral Skills Model Analysis

    Science.gov (United States)

    Kiene, Susan M.; Fisher, William A.; Shuper, Paul A.; Cornman, Deborah H.; Christie, Sarah; MacDonald, Susan; Pillay, Sandy; Mahlase, Gethwana; Fisher, Jeffrey D.

    2014-01-01

    The current study applied the Information—Motivation—Behavioral Skills (IMB) model (J. D. Fisher & Fisher, 1992; W. A. Fisher & Fisher, 1993) to identify factors associated with HIV transmission risk behavior among HIV-infected South Africans receiving antiretroviral therapy (ART), a population of considerable significance for curtailing, or maintaining, South Africa’s generalized HIV epidemic. HIV prevention information, HIV prevention motivation, HIV prevention behavioral skills, and HIV transmission risk behavior were assessed in a sample of 1,388 South Africans infected with HIV and receiving ART in 16 clinics in KwaZulu-Natal, South Africa. Results confirmed the assumptions of the IMB model and demonstrated that HIV prevention information and HIV prevention motivation work through HIV prevention behavioral skills to affect HIV transmission risk behavior in this population. Subanalyses confirmed these relationships for HIV transmission risk behavior overall and for HIV transmission risk behavior with partners perceived to be HIV-negative or HIV-status unknown. A consistent pattern of gender differences showed that for men, HIV prevention information and HIV prevention motivation may have direct links with HIV preventive behavior, while for women, the effects of HIV prevention information and HIV prevention motivation work through HIV prevention behavioral skills to affect HIV preventive behavior. These IMB model-based findings suggest directions for HIV prevention interventions with South African men and women living with HIV and on ART as an important component of overall strategies to contain South Africa’s generalized HIV epidemic. PMID:23477576

  6. Using HIV&AIDS statistics in pre-service Mathematics Education to integrate HIV&AIDS education.

    Science.gov (United States)

    van Laren, Linda

    2012-12-01

    In South Africa, the HIV&AIDS education policy documents indicate opportunities for integration across disciplines/subjects. There are different interpretations of integration/inclusion and mainstreaming HIV&AIDS education, and numerous levels of integration. Integration ensures that learners experience the disciplines/subjects as being linked and related, and integration is required to support and expand the learners' opportunities to attain skills, acquire knowledge and develop attitudes and values across the curriculum. This study makes use of self-study methodology where I, a teacher educator, aim to improve my practice through including HIV&AIDS statistics in Mathematics Education. This article focuses on how I used HIV&AIDS statistics to facilitate pre-service teacher reflection and introduce them to integration of HIV&AIDS education across the curriculum. After pre-service teachers were provided with HIV statistics, they drew a pie chart which graphically illustrated the situation and reflected on issues relating to HIV&AIDS. Three themes emerged from the analysis of their reflections. The themes relate to the need for further HIV&AIDS education, the changing pastoral role of teachers and the changing context of teaching. This information indicates that the use of statistics is an appropriate means of initiating the integration of HIV&AIDS education into the academic curriculum.

  7. Facilitators and Barriers to Discussing HIV Prevention With Adolescents: Perspectives of HIV-Infected Parents

    Science.gov (United States)

    Reis, Janet S.; Weber, Kathleen M.

    2013-01-01

    Objectives. We examined HIV-infected parents’ conversations about HIV prevention with their uninfected children, including what facilitated or hindered communication. Methods. Parents with HIV/AIDS (n = 90) who had children aged 10 to 18 years were recruited for a mixed method study from 2009 to 2010. Interviews assessed facilitators and barriers to discussing HIV prevention. A questionnaire identified the frequency and content of conversations, parental confidence level, and perceived importance of discussing preventive topics. Results. Eighty-one percent of parents reported “sometimes” or “often” communicating about HIV prevention. A subset of parents found these conversations difficult; 44% indicated their desire for support. Facilitators to communication included utilizing support, focusing on the benefits of talking, and having a previous relationship with one’s child. Barriers to discussions included fear of negative consequences, living in denial, and lacking a parental role model who discussed safer sex. Parents varied as to how they believed their HIV status affected communication. Those who did not disclose their HIV status to their children reported less frequent communication; self-efficacy partially mediated this relationship. Conclusions. Findings highlighted the need for communication skills training that support HIV-infected parents in their efforts to discuss HIV-related information with adolescents. PMID:23763390

  8. Faith and HIV prevention: the conceptual framing of HIV prevention among Pentecostal Batswana teenagers.

    Science.gov (United States)

    Mpofu, Elias; Nkomazana, Fidelis; Muchado, Jabulani A; Togarasei, Lovemore; Bingenheimer, Jeffrey Bart

    2014-03-05

    There is a huge interest by faith-based organizations (FBOs) in sub-Saharan Africa and elsewhere in HIV prevention interventions that build on the religious aspects of being. Successful partnerships between the public health services and FBOs will require a better understanding of the conceptual framing of HIV prevention by FBOS to access for prevention intervention, those concepts the churches of various denominations and their members would support or endorse. This study investigated the conceptual framing of HIV prevention among church youths in Botswana;--a country with one of the highest HIV prevalence in the world. Participants were 213 Pentecostal church members (67% female; age range 12 to 23 years; median age=19 years). We engaged the participants in a mixed-method inductive process to collect data on their implicit framing of HIV prevention concepts, taking into account the centrality of religion concepts to them and the moderating influences of age, gender and sexual experience. After, we analysed the data using multi-dimensional scaling (MDS) and hierarchical cluster analysis (HCA) to map the ways the church youths framed HIV prevention. The findings suggest the church youth to conceptually frame their HIV prevention from both faith-oriented and secular-oriented perspectives, while prioritizing the faith-oriented concepts based on biblical teachings and future focus. In their secular-oriented framing of HIV prevention, the church youths endorsed the importance to learn the facts about HIV and AIDS, understanding of community norms that increased risk for HIV and prevention education. However, components of secular-oriented framing of HIV prevention concepts were comparatively less was well differentiated among the youths than with faith-oriented framing, suggesting latent influences of the church knowledge environment to undervalue secular oriented concepts. Older and sexually experienced church youths in their framing of HIV prevention valued future

  9. Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

    Science.gov (United States)

    Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa

    2018-01-01

    The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461

  10. "I never thought that it would happen … " Experiences of HIV seroconverters among HIV-discordant partnerships in a prospective HIV prevention study in Kenya.

    Science.gov (United States)

    Ngure, Kenneth; Vusha, Sophie; Mugo, Nelly; Emmanuel-Fabula, Mira; Ngutu, Mariah; Celum, Connie; Baeten, Jared M; Heffron, Renee

    2016-12-01

    In spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples' needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples' communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples' counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms.

  11. Bundle Branch Block

    Science.gov (United States)

    ... known cause. Causes can include: Left bundle branch block Heart attacks (myocardial infarction) Thickened, stiffened or weakened ... myocarditis) High blood pressure (hypertension) Right bundle branch block A heart abnormality that's present at birth (congenital) — ...

  12. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  13. HMBA Enhances Prostratin-Induced Activation of Latent HIV-1 via Suppressing the Expression of Negative Feedback Regulator A20/TNFAIP3 in NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Duchu Chen

    2016-01-01

    Full Text Available In the past decade, much emphasis has been put on the transcriptional activation of HIV-1, which is proposed as a promised strategy for eradicating latent HIV-1 provirus. Two drugs, prostratin and hexamethylene bisacetamide (HMBA, have shown potent effects as inducers for releasing HIV-1 latency when used alone or in combination, although their cellular target(s are currently not well understood, especially under drug combination. Here, we have shown that HMBA and prostratin synergistically release HIV-1 latency via different mechanisms. While prostratin strongly stimulates HMBA-induced HIV-1 transcription via improved P-TEFb activation, HMBA is capable of boosting NF-κB-dependent transcription initiation by suppressing prostratin-induced expression of the deubiquitinase A20, a negative feedback regulator in the NF-κB signaling pathway. In addition, HMBA was able to increase prostratin-induced phosphorylation and degradation of NF-κB inhibitor IκBα, thereby enhancing and prolonging prostratin-induced nuclear translocation of NF-κB, a prerequisite for stimulation of transcription initiation. Thus, by blocking the negative feedback circuit, HMBA functions as a signaling enhancer of the NF-κB signaling pathway.

  14. HIV surveillance in complex emergencies.

    Science.gov (United States)

    Salama, P; Dondero, T J

    2001-04-01

    Many studies have shown a positive association between both migration and temporary expatriation and HIV risk. This association is likely to be similar or even more pronounced for forced migrants. In general, HIV transmission in host-migrant or host-forced-migrant interactions depends on the maturity of the HIV epidemic in both the host and the migrant population, the relative seroprevalence of HIV in the host and the migrant population, the prevalence of other sexually transmitted infections (STIs) that may facilitate transmission, and the level of sexual interaction between the two communities. Complex emergencies are the major cause of mass population movement today. In complex emergencies, additional factors such as sexual interaction between forced-migrant populations and the military; sexual violence; increasing commercial sex work; psychological trauma; and disruption of preventive and curative health services may increase the risk for HIV transmission. Despite recent success in preventing HIV infection in stable populations in selected developing countries, internally displaced persons and refugees (or forced migrants) have not been systematically included in HIV surveillance systems, nor consequently in prevention activities. Standard surveillance systems that rely on functioning health services may not provide useful data in many complex emergency settings. Secondary sources can provide some information in these settings. Little attempt has been made, however, to develop innovative HIV surveillance systems in countries affected by complex emergencies. Consequently, data on the HIV epidemic in these countries are scarce and HIV prevention programs are either not implemented or interventions are not effectively targeted. Second generation surveillance methods such as cross-sectional, population-based surveys can provide rapid information on HIV, STIs, and sexual behavior. The risks for stigmatization and breaches of confidentiality must be recognized

  15. Alcohol and condom use among HIV-positive and HIV-negative female sex workers in Nagaland, India.

    Science.gov (United States)

    Nuken, Amenla; Kermode, Michelle; Saggurti, Niranjan; Armstrong, Greg; Medhi, Gajendra Kumar

    2013-09-01

    This study examines the relationship between alcohol use, HIV status, and condom use among female sex workers in Nagaland, India. We analyzed data from a cross-sectional survey undertaken in 2009, using descriptive and multivariate statistics. Out of 417 female sex workers, one-fifth used alcohol daily and one-tenth were HIV-positive. HIV-positive female sex workers were more likely than HIV-negative female sex workers to consume alcohol daily (30.2% vs. 18.0%). HIV-positive daily alcohol users reported lower condom use at last sex with regular clients compared to HIV-positive non-daily alcohol users (46.2% vs. 79.3%), a relationship not evident among HIV-negative female sex workers. There is a need to promote awareness of synergies between alcohol use and HIV, and to screen for problematic alcohol use among female sex workers in order to reduce the spread of HIV.

  16. Community study of the relative impact of HIV-1 and HIV-2 on intrathoracic tuberculosis

    DEFF Research Database (Denmark)

    Seng, R; Gustafson, P; Gomes, VF

    2002-01-01

    BACKGROUND: HIV-1 infection is associated with an increased incidence of and mortality from tuberculosis. Few community studies have examined the effect of HIV-2 on tuberculosis. METHODS: We investigated the association between HIV-1, HIV-2 and active tuberculosis in four districts (population 42...

  17. A comparison of two measures of HIV diversity in multi-assay algorithms for HIV incidence estimation.

    Directory of Open Access Journals (Sweden)

    Matthew M Cousins

    Full Text Available Multi-assay algorithms (MAAs can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.Both MAAs included two serologic assays (LAg-Avidity assay and BioRad-Avidity assay, HIV viral load, and an HIV diversity assay. HIV diversity was quantified using either a high resolution melting (HRM diversity assay that does not require HIV sequencing (HRM score for a 239 base pair env region or sequence ambiguity (the percentage of ambiguous bases in a 1,302 base pair pol region. Samples were classified as MAA positive (likely from individuals with recent HIV infection if they met the criteria for all of the assays in the MAA. The following performance characteristics were assessed: (1 the proportion of samples classified as MAA positive as a function of duration of infection, (2 the mean window period, (3 the shadow (the time period before sample collection that is being assessed by the MAA, and (4 the accuracy of cross-sectional incidence estimates for three cohort studies.The proportion of samples classified as MAA positive as a function of duration of infection was nearly identical for the two MAAs. The mean window period was 141 days for the HRM-based MAA and 131 days for the sequence ambiguity-based MAA. The shadows for both MAAs were <1 year. Both MAAs provided cross-sectional HIV incidence estimates that were very similar to longitudinal incidence estimates based on HIV seroconversion.MAAs that include the LAg-Avidity assay, the BioRad-Avidity assay, HIV viral load, and HIV diversity can provide accurate HIV incidence estimates. Sequence ambiguity measures obtained using a commercially-available HIV genotyping system can be used as an alternative to HRM scores in MAAs for cross-sectional HIV incidence estimation.

  18. A Comparison of Two Measures of HIV Diversity in Multi-Assay Algorithms for HIV Incidence Estimation

    Science.gov (United States)

    Cousins, Matthew M.; Konikoff, Jacob; Sabin, Devin; Khaki, Leila; Longosz, Andrew F.; Laeyendecker, Oliver; Celum, Connie; Buchbinder, Susan P.; Seage, George R.; Kirk, Gregory D.; Moore, Richard D.; Mehta, Shruti H.; Margolick, Joseph B.; Brown, Joelle; Mayer, Kenneth H.; Kobin, Beryl A.; Wheeler, Darrell; Justman, Jessica E.; Hodder, Sally L.; Quinn, Thomas C.; Brookmeyer, Ron; Eshleman, Susan H.

    2014-01-01

    Background Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence. Methods Both MAAs included two serologic assays (LAg-Avidity assay and BioRad-Avidity assay), HIV viral load, and an HIV diversity assay. HIV diversity was quantified using either a high resolution melting (HRM) diversity assay that does not require HIV sequencing (HRM score for a 239 base pair env region) or sequence ambiguity (the percentage of ambiguous bases in a 1,302 base pair pol region). Samples were classified as MAA positive (likely from individuals with recent HIV infection) if they met the criteria for all of the assays in the MAA. The following performance characteristics were assessed: (1) the proportion of samples classified as MAA positive as a function of duration of infection, (2) the mean window period, (3) the shadow (the time period before sample collection that is being assessed by the MAA), and (4) the accuracy of cross-sectional incidence estimates for three cohort studies. Results The proportion of samples classified as MAA positive as a function of duration of infection was nearly identical for the two MAAs. The mean window period was 141 days for the HRM-based MAA and 131 days for the sequence ambiguity-based MAA. The shadows for both MAAs were cross-sectional HIV incidence estimates that were very similar to longitudinal incidence estimates based on HIV seroconversion. Conclusions MAAs that include the LAg-Avidity assay, the BioRad-Avidity assay, HIV viral load, and HIV diversity can provide accurate HIV incidence estimates. Sequence ambiguity measures obtained using a commercially-available HIV genotyping system can be used as an alternative to HRM scores in MAAs for cross-sectional HIV incidence estimation. PMID:24968135

  19. A randomized trial comparing surgeon-administered intraoperative transversus abdominis plane block with anesthesiologist-administered transcutaneous block.

    Science.gov (United States)

    Narasimhulu, D M; Scharfman, L; Minkoff, H; George, B; Homel, P; Tyagaraj, K

    2018-04-27

    Injection of local anesthetic into the transversus abdominis plane (TAP block) decreases systemic morphine requirements after abdominal surgery. We compared intraoperative surgeon-administered TAP block (surgical TAP) to anesthesiologist-administered transcutaneous ultrasound-guided TAP block (conventional TAP) for post-cesarean analgesia. We hypothesized that surgical TAP blocks would take less time to perform than conventional TAP blocks. We performed a randomized trial, recruiting 41 women undergoing cesarean delivery under neuraxial anesthesia, assigning them to either surgical TAP block (n=20) or conventional TAP block (n=21). Time taken to perform the block was the primary outcome, while postoperative pain scores and 24-hour opioid requirements were secondary outcomes. Student's t-test was used to compare block time and Kruskal-Wallis test opioid consumption and pain-scores. Time taken to perform the block (2.4 vs 12.1 min, P consumption (P=0.17) and postoperative pain scores at 4, 8, 24 and 48 h were not significantly different between the groups. Surgical TAP blocks are feasible and less time consuming than conventional TAP blocks, while providing comparable analgesia after cesarean delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Understanding HIV transmission risk behavior among HIV-infected South Africans receiving antiretroviral therapy: an information--motivation--behavioral skills model analysis.

    Science.gov (United States)

    Kiene, Susan M; Fisher, William A; Shuper, Paul A; Cornman, Deborah H; Christie, Sarah; Macdonald, Susan; Pillay, Sandy; Mahlase, Gethwana; Fisher, Jeffrey D

    2013-08-01

    The current study applied the Information-Motivation-Behavioral Skills (IMB) model (Fisher & Fisher, 1992; Fisher & Fisher, 1993) to identify factors associated with human immunodeficiency virus (HIV) transmission risk behavior among HIV-infected South Africans receiving antiretroviral therapy (ART), a population of considerable significance for curtailing, or maintaining, South Africa's generalized HIV epidemic. HIV prevention information, HIV prevention motivation, HIV prevention behavioral skills, and HIV transmission risk behavior were assessed in a sample of 1,388 South Africans infected with HIV and receiving ART in 16 clinics in KwaZulu-Natal, South Africa. Findings confirmed the assumptions of the IMB model and demonstrated that HIV prevention information and HIV prevention motivation work through HIV prevention behavioral skills to affect HIV transmission risk behavior in this population. Subanalyses confirmed these relationships for HIV transmission risk behavior overall and for HIV transmission risk behavior with partners perceived to be HIV-negative or HIV-status unknown. A consistent pattern of gender differences showed that for men, HIV prevention information and HIV prevention motivation may have direct links with HIV preventive behavior, whereas for women, the effect of HIV prevention motivation works through HIV prevention behavioral skills to affect HIV preventive behavior. These IMB model-based findings suggest directions for HIV prevention interventions with South African men and women living with HIV and on ART as an important component of overall strategies to contain South Africa's generalized HIV epidemic. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  1. Trans-dissemination of exosomes from HIV-1-infected cells fosters both HIV-1 trans-infection in resting CD4+ T lymphocytes and reactivation of the HIV-1 reservoir.

    Science.gov (United States)

    Chiozzini, Chiara; Arenaccio, Claudia; Olivetta, Eleonora; Anticoli, Simona; Manfredi, Francesco; Ferrantelli, Flavia; d'Ettorre, Gabriella; Schietroma, Ivan; Andreotti, Mauro; Federico, Maurizio

    2017-09-01

    Intact HIV-1 and exosomes can be internalized by dendritic cells (DCs) through a common pathway leading to their transmission to CD4 + T lymphocytes by means of mechanisms defined as trans-infection and trans-dissemination, respectively. We previously reported that exosomes from HIV-1-infected cells activate both uninfected quiescent CD4 + T lymphocytes, which become permissive to HIV-1, and latently infected cells, with release of HIV-1 particles. However, nothing is known about the effects of trans-dissemination of exosomes produced by HIV-1-infected cells on uninfected or latently HIV-1-infected CD4 + T lymphocytes. Here, we report that trans-dissemination of exosomes from HIV-1-infected cells induces cell activation in resting CD4 + T lymphocytes, which appears stronger with mature than immature DCs. Using purified preparations of both HIV-1 and exosomes, we observed that mDC-mediated trans-dissemination of exosomes from HIV-1-infected cells to resting CD4 + T lymphocytes induces efficient trans-infection and HIV-1 expression in target cells. Most relevant, when both mDCs and CD4 + T lymphocytes were isolated from combination anti-retroviral therapy (ART)-treated HIV-1-infected patients, trans-dissemination of exosomes from HIV-1-infected cells led to HIV-1 reactivation from the viral reservoir. In sum, our data suggest a role of exosome trans-dissemination in both HIV-1 spread in the infected host and reactivation of the HIV-1 reservoir.

  2. Being and Becoming “Fully Human” in an Hiv-Positive World: Hiv ...

    African Journals Online (AJOL)

    Feminists have researched the link between gender and HIV/AIDS and shown that women are not always morally responsible for being HIV-positive. This article contributes to the debate by presenting a systematic discussion of women's experience of HIV/AIDS and spirituality. It offers a model of full humanity that interprets ...

  3. Correlation between HIV-1 genotype and clinical progression in HIV/AIDS patients in Surabaya, Indonesia

    Science.gov (United States)

    Rachman, B. E.; Khairunisa, S. Q.; Witaningrum, A. M.; Yunifiar, M. Q.; Nasronudin

    2018-03-01

    Several factors such as host and viral factors can affect the progression of HIV/AIDS. This study aims to identify the correlation viral factors, especially the HIV-1 subtype with HIV/AIDS progression. Inpatient HIV/AIDS during the period March to September 2017 and willing to participate are included in the study. Historical data of disease and treatment was taken by medical record. Blood samples were amplified, sequenced and undergone phylogenetic analysis. Linear regression analysis was used to estimate beta coefficient (β) and 95%CI of HIV/AIDS progression (measured by the CD4 change rate, ΔCD4 cell count/time span in months).This study has 17 samples. The HIV-1 subtype was dominated by CRF01_AE (81.8%) followed by subtype B (18.2%). There was significant correlation between subtype HIV-1 (p = 0.04) and body mass index (p = 0.038) with HIV/AIDS clinical stage. Many factors were assumed to be correlated with increased rate of CD4, but we only subtype HIV-1 had a significant correlation (p = 0.024) with it. From multivariate analysis, we also found that subtype HIV-1 had a significant correlation (β = 0.788, 95%CI: 17.5-38.6, p = 0.004).

  4. Motivators of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness studies.

    Science.gov (United States)

    Dhalla, Shayesta; Poole, Gary

    2011-11-01

    HIV vaccine preparedness studies (VPS) are important precursors to HIV vaccine trials. As well, they contribute to an understanding of motivators and barriers for participation in hypothetical HIV vaccine trials. Motivators can take the form of altruism and a desire for social benefits. Perceived personal benefits, including psychological, personal, and financial well-being, may also motivate participation. The authors performed a systematic review of HIV VPS using the Cochrane Database for Systematic Reviews, Medline, PubMed, Embase, and Google Scholar. The authors independently searched the literature for individual HIV VPS that examined motivators of participation in a hypothetical HIV vaccine trial, using the same search strategy. As the denominators employed in the literature varied across studies, the denominators were standardized to the number of respondents per survey item, regardless of their willingness to participate (WTP) in an HIV vaccine trial. The authors retrieved eight studies on social benefits (i.e., altruism) and 11 studies on personal benefits conducted in the Organization for Economic Co-operation and Development (OECD) countries, as well as 19 studies on social benefits and 20 studies on personal benefits in the non-OECD countries. Various different forms of altruism were found to be the major motivators for participation in an HIV vaccine trial in both the OECD and the non-OECD countries. In a large number of studies, protection from HIV was cited as a personal motivator for participation in a hypothetical HIV vaccine trial in the OECD and the non-OECD countries. Knowledge of motivators can inform and target recruitment for HIV vaccine trials, although it must be remembered that hypothetical motivators may not always translate into motivators in an actual vaccine trial.

  5. Religion and HIV in Tanzania: influence of religious beliefs on HIV stigma, disclosure, and treatment attitudes

    Directory of Open Access Journals (Sweden)

    Ostermann Jan

    2009-03-01

    Full Text Available Abstract Background Religion shapes everyday beliefs and activities, but few studies have examined its associations with attitudes about HIV. This exploratory study in Tanzania probed associations between religious beliefs and HIV stigma, disclosure, and attitudes toward antiretroviral (ARV treatment. Methods A self-administered survey was distributed to a convenience sample of parishioners (n = 438 attending Catholic, Lutheran, and Pentecostal churches in both urban and rural areas. The survey included questions about religious beliefs, opinions about HIV, and knowledge and attitudes about ARVs. Multivariate logistic regression analysis was performed to assess how religion was associated with perceptions about HIV, HIV treatment, and people living with HIV/AIDS. Results Results indicate that shame-related HIV stigma is strongly associated with religious beliefs such as the belief that HIV is a punishment from God (p Conclusion The decision to start ARVs hinged primarily on education-level and knowledge about ARVs rather than on religious factors. Research results highlight the influence of religious beliefs on HIV-related stigma and willingness to disclose, and should help to inform HIV-education outreach for religious groups.

  6. Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients among the HIV-2 cohort of The West African Database to evaluate AIDS collaboration

    Science.gov (United States)

    Tchounga, Boris K; Inwoley, Andre; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Bado, Guillaume; Minga, Albert; Hawerlander, Denise; Kane, Coumba; Eholie, Serge P; Dabis, François; Ekouevi, Didier K

    2014-01-01

    Introduction West Africa is characterized by the circulation of HIV-1 and HIV-2. The laboratory diagnosis of these two infections as well as the choice of a first-line antiretroviral therapy (ART) is challenging, considering the limited access to second-line regimens. This study aimed at confirming the classification of HIV-2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. Method A cross-sectional survey was conducted from March to December 2012 in Burkina Faso, Côte d’Ivoire and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according to the national HIV testing algorithms. A 5-ml blood sample was collected from each patient and tested in a single reference laboratory in Côte d’Ivoire (CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII® (HIV-1&2 ImmunoComb BiSpot – Alere) and an in-house ELISA test, approved by the French National AIDS and hepatitis Research Agency (ANRS). Results A total of 547 patients were included; 57% of them were initially classified as HIV-2 and 43% as HIV-1&2 dually reactive. Half of the patients had CD4≥500 cells/mm3 and 68.6% were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were confirmed as HIV-2 with ImmunoCombII® and in-house ELISA while 16 (5.1%) and 9 (2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69; p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive, only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII® and in-house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV-2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples (54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave discordant results for 65 samples (11.9%). Conclusions Patients with HIV-2 mono-infection are correctly

  7. Prevalence and Correlates of Non-Disclosure of HIV Serostatus to Sex partners among HIV-Infected Female Sex Workers and HIV-infected Male Clients of Female Sex Workers in India

    Science.gov (United States)

    Raj, Anita; Mahapatra, Bidhubhusan; Cheng, Debbie M.; Coleman, Sharon; Bridden, Carly; Battala, Madhusudana; Silverman, Jay G.; Pardeshi, Manoj H.; Samet, Jeffrey H.

    2013-01-01

    This study examines non-disclosure of HIV serostatus to sex partners among HIV-infected adults involved with transactional sex in Mumbai, India. Surveys were conducted with HIV-infected female sex workers (n = 211) and infected male clients (n = 205) regarding HIV knowledge, awareness of sex partners’ HIV serostatus, alcohol use, transactional sex involvement post-HIV diagnosis and non-disclosure of HIV serostatus. Gender-stratified multiple logistic regression models were used for analysis. Non-disclosure of one’s serostatus to all sex partners was reported by almost three-fifths of females and two-fifths of males. Predictors of non-disclosure included lack of correct knowledge about HIV and no knowledge of sex partners’ HIV serostatus. Among females, recent alcohol consumption also predicted non-disclosure. Among males, 10 + paid sexual partners in the year following HIV diagnosis predicted non-disclosure. Secondary HIV prevention efforts in India require greater focus on HIV disclosure communication and integrated alcohol and sexual risk reduction. PMID:22810892

  8. SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells.

    Directory of Open Access Journals (Sweden)

    Ruonan Zhang

    Full Text Available SAMHD1 restricts the replication of HIV-1 and other retroviruses in human myeloid and resting CD4(+ T cells and that is counteracted in SIV and HIV-2 by the Vpx accessory protein. The protein is a phosphohydrolase that lowers the concentration of deoxynucleoside triphosphates (dNTP, blocking reverse transcription of the viral RNA genome. Polymorphisms in the gene encoding SAMHD1 are associated with Aicardi-Goutières Syndrome, a neurological disorder characterized by increased type-I interferon production. SAMHD1 is conserved in mammals but its role in restricting virus replication and controlling interferon production in non-primate species is not well understood. We show that SAMHD1 is catalytically active and expressed at high levels in mouse spleen, lymph nodes, thymus and lung. siRNA knock-down of SAMHD1 in bone marrow-derived macrophages increased their susceptibility to HIV-1 infection. shRNA knock-down of SAMHD1 in the murine monocytic cell-line RAW264.7 increased its susceptibility to HIV-1 and murine leukemia virus and increased the levels of the dNTP pool. In addition, SAMHD1 knock-down in RAW264.7 cells induced the production of type-I interferon and several interferon-stimulated genes, modeling the situation in Aicardi-Goutières Syndrome. Our findings suggest that the role of SAMHD1 in restricting viruses is conserved in the mouse. The RAW264.7 cell-line serves as a useful tool to study the antiviral and innate immune response functions of SAMHD1.

  9. Predictors of HIV/AIDS confirmation and differences by guardian status in HIV+ adolescents in Jamaica.

    Science.gov (United States)

    Pilgrim, N; Kershaw, T; Pierre, R B; Moore, J; Palmer, P; Davis, D; Christie, C D C

    2008-06-01

    Approximately 25% of the cumulative AIDS cases in Jamaica involve adolescents and young adults. However the lives of adolescents living with HIV within Jamaica and the Caribbean have been understudied. (1) To describe the sociodemographic characteristics of HIV+ Jamaican adolescents who have ever been a part of the Kingston Paediatric/Perinatal HIV Programme (KPAIDS) from September 1, 2002 to August 31, 2006 (2). To identify predictors of HIV/AIDS confirmation as well as factors associated or uniquely present in these adolescents by their guardian status. Seventy-two HIV+ adolescents, ages 10-19 years, were included. Factors studied included demographics as well as time to and time between HIV and AIDS confirmation. Data were analyzed by bivariate and multivariate statistics. The mean age of the adolescents was 12.6 +/- 2.8 years with slightly more males (52.8%) in the programme. There were equal proportions of adolescents living with HIV as with AIDS (43.1%). There were equal proportions who were lost to follow-up or deceased (8.3%). Twenty-two of them lived with parents, 25 with guardians and 18 in residential institutions. The primary mode of transmission was perinatal infection (68.1%), followed by sexual (20.8%), blood transfusion (2.9%) and unknown (8.3%). The mean time from HIV exposure to HIV confirmation and AIDS confirmation in mother-to-child transmission (MTCT) cases were 8.0 +/- 2.9 years and 9.6 +/- 3.3 years, respectively. In the multivariate analysis model, age and gender were significant in predicting time from HIV exposure to HIV confirmation. The majority of HIV-positive adolescents reside with parents and guardians and this might indicate support in spite of stigma and discrimination. However; the mean time to HIV confirmation in MTCT cases is quite long and must be reduced.

  10. From 'half-dead' to being 'free': resistance to HIV stigma, self-disclosure and support for PMTCT/HIV care among couples living with HIV in Kenya.

    Science.gov (United States)

    Spangler, Sydney A; Abuogi, Lisa L; Akama, Eliud; Bukusi, Elizabeth A; Helova, Anna; Musoke, Pamela; Nalwa, Wafula Z; Odeny, Thomas A; Onono, Maricianah; Wanga, Iris; Turan, Janet M

    2018-05-01

    In sub-Saharan Africa, self-disclosure of HIV-positive status may be a pivotal action for improving access to prevention of mother-to-child transmission services. However, understanding of HIV stigma and disclosure, and their effects on demand for care remains incomplete - particularly in the current context of new antiretroviral therapy guidelines. The purpose of this study was to explore these issues among self-disclosed couples living in southwest Kenya. We conducted 38 in-depth interviews with HIV-positive pregnant or postpartum women and their male partners. Of the 19 couples, 10 were HIV seroconcordant and 9 were serodiscordant. The textual analysis showed that HIV stigma continues to restrict full participation in community life and limit access to care by promoting fear, isolation and self-censorship. Against this backdrop, however, participants' narratives revealed varying forms and degrees of resistance to HIV stigma, which appeared to both produce and emerge from acts of self-disclosure. Such disclosure enabled participants to overcome fears and gain critical support for engaging in HIV care while further resisting HIV stigma. These findings suggest that programme interventions designed explicitly to stimulate and support processes of HIV stigma resistance and safe self-disclosure may be key to improving demand for and retention in HIV services.

  11. An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G.

    Science.gov (United States)

    Ejima, Tomohiko; Hirota, Mayuko; Mizukami, Tamio; Otsuka, Masami; Fujita, Mikako

    2011-10-01

    Human apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) 3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory function of Vif is related to its ability to degrade A3G in the proteasome. This finding prompted us to examine the activities of 4-(dimethylamino)-2,6-bis[(N-(2-[(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine (SN-2) and SN-3. We found that 5 µM SN-2 increases the expression of A3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. The proteasome inhibitor MG-132 increased the level of both A3G and Vif expression. These results demonstrate that A3G is ubiquitinated and degraded in the proteasome by a factor other than Vif, and that SN-2 selectively inhibits these processes. Furthermore, 5 µM SN-2 significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.

  12. Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission.

    Directory of Open Access Journals (Sweden)

    Anatoli Kamali

    Full Text Available HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.

  13. Creating an African HIV Clinical Research and Prevention Trials Network: HIV Prevalence, Incidence and Transmission

    Science.gov (United States)

    Kamali, Anatoli; Price, Matt A.; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J.; Anzala, Omu; Latka, Mary H.; Bekker, Linda-Gail; Kaleebu, Pontiano; Asiki, Gershim; Ssetaala, Ali; Ruzagira, Eugene; Allen, Susan; Farmer, Paul; Hunter, Eric; Mutua, Gaudensia; Makkan, Heeran; Tichacek, Amanda; Brill, Ilene K.; Fast, Pat; Stevens, Gwynn; Chetty, Paramesh; Amornkul, Pauli N.; Gilmour, Jill

    2015-01-01

    HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner. PMID:25602351

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV or transmitting it to someone else. Biological effects of drugs. Drug misuse and addiction can affect a person's overall health, thereby altering susceptibility to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury ...

  15. Perceptions of HIV-related health services in Zambia for people with disabilities who are HIV-positive

    Science.gov (United States)

    Nixon, Stephanie A; Cameron, Cathy; Hanass-Hancock, Jill; Simwaba, Phillimon; Solomon, Patricia E; Bond, Virginia A; Menon, Anitha; Richardson, Emma; Stevens, Marianne; Zack, Elisse

    2014-01-01

    Introduction Despite the emerging body of literature on increased vulnerability to HIV among people with disabilities (PWDs), there is a dearth of evidence related to experiences of PWDs who have become HIV-positive. This priority was identified by a disability advocacy organization in Lusaka, Zambia, where the prevalence of HIV and of disability is each approximately 15%. The purpose of this study was to explore perceptions and experiences of HIV-related health services for PWDs who are also living with HIV in Lusaka, Zambia. Methods This qualitative, interpretive study involved in-depth, semi-structured, one-on-one interviews with two groups of participants in Lusaka, Zambia: 21 PWDs who had become HIV-positive, and 11 people working in HIV and/or disability. PWDs had physical, hearing, visual and/or intellectual impairments. Interviews were conducted in English, Nyanja, Bemba or Zambian sign language. Descriptive and thematic analyses were conducted by a multidisciplinary, international research team. Results Participants described their experiences with HIV-related health services in terms of the challenges they faced. In particular, they encountered three main challenges while seeking care and treatment: (1) disability-related discrimination heightened when seeking HIV services, (2) communication barriers and related concerns with confidentiality, and (3) movement and mobility challenges related to seeking care and collecting antiretroviral therapy. These experiences were further shaped by participants’ profound concerns about poverty and unmet basic needs. Discussion This study demonstrates how PWDs who are HIV-positive have the same HIV care, treatment and support needs as able-bodied counterparts, but face avoidable barriers to care. Many challenges mirror concerns identified with HIV prevention, suggesting that efforts to promote inclusion and reduce stigma could have widespread benefits. Conclusions Despite the growing body of literature on increased

  16. Perceptions of HIV-related health services in Zambia for people with disabilities who are HIV-positive.

    Science.gov (United States)

    Nixon, Stephanie A; Cameron, Cathy; Hanass-Hancock, Jill; Simwaba, Phillimon; Solomon, Patricia E; Bond, Virginia A; Menon, Anitha; Richardson, Emma; Stevens, Marianne; Zack, Elisse

    2014-01-01

    Despite the emerging body of literature on increased vulnerability to HIV among people with disabilities (PWDs), there is a dearth of evidence related to experiences of PWDs who have become HIV-positive. This priority was identified by a disability advocacy organization in Lusaka, Zambia, where the prevalence of HIV and of disability is each approximately 15%. The purpose of this study was to explore perceptions and experiences of HIV-related health services for PWDs who are also living with HIV in Lusaka, Zambia. This qualitative, interpretive study involved in-depth, semi-structured, one-on-one interviews with two groups of participants in Lusaka, Zambia: 21 PWDs who had become HIV-positive, and 11 people working in HIV and/or disability. PWDs had physical, hearing, visual and/or intellectual impairments. Interviews were conducted in English, Nyanja, Bemba or Zambian sign language. Descriptive and thematic analyses were conducted by a multidisciplinary, international research team. Participants described their experiences with HIV-related health services in terms of the challenges they faced. In particular, they encountered three main challenges while seeking care and treatment: (1) disability-related discrimination heightened when seeking HIV services, (2) communication barriers and related concerns with confidentiality, and (3) movement and mobility challenges related to seeking care and collecting antiretroviral therapy. These experiences were further shaped by participants' profound concerns about poverty and unmet basic needs. This study demonstrates how PWDs who are HIV-positive have the same HIV care, treatment and support needs as able-bodied counterparts, but face avoidable barriers to care. Many challenges mirror concerns identified with HIV prevention, suggesting that efforts to promote inclusion and reduce stigma could have widespread benefits. Despite the growing body of literature on increased risk of exposure to HIV among HIV-negative PWDs, this is

  17. HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection

    Directory of Open Access Journals (Sweden)

    Angeline Rouers

    2017-07-01

    Full Text Available HIV-specific broadly neutralizing antibodies (bnAbs have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs, multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57+ and HLA-B*57− ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.

  18. Thinking Outside the Block: An Innovative Alternative to 4X4 Block Scheduling.

    Science.gov (United States)

    Frank, Myra

    2002-01-01

    Introduces a 4x1 block scheduling method that was developed as an alternative to 4x4 block scheduling. Schedules Fridays for summer school, test preparation, and enrichment and elective courses. Includes suggestions on how to alleviate drawbacks of the 4x1 block schedule. (YDS)

  19. Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

    African Journals Online (AJOL)

    out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated model using Web cutter Version 2.0, and cytogenetic analysis. 339 restriction enzymes from Promega database, 10 HIV-1/SIVcpz genes, 10 HIV-2/SIVsmm genes and 10 other SIV genes. Gene sequences were fed into Web ...

  20. a reflection on the impact of HIV discordance on child HIV infection

    African Journals Online (AJOL)

    cqq1a

    2010-05-09

    May 9, 2010 ... discordant couples with an HIV positive man is almost the same as that of discordant couples with an HIV positive woman [1]. There is a need to better analyze the impact of HIV sero-discordance in the context of pregnancy and prevention of mother to child transmission (PMTCT). In general, PMTCT ...

  1. Decreased chronic morbidity but elevated HIV associated cytokine levels in HIV-infected older adults receiving HIV treatment: benefit of enhanced access to care?

    Directory of Open Access Journals (Sweden)

    Portia C Mutevedzi

    Full Text Available The association of HIV with chronic morbidity and inflammatory markers (cytokines in older adults (50+years is potentially relevant for clinical care, but data from African populations is scarce.To examine levels of chronic morbidity by HIV and ART status in older adults (50+years and subsequent associations with selected pro-inflammatory cytokines and body mass index.Ordinary, ordered and generalized ordered logistic regression techniques were employed to compare chronic morbidity (heart disease (angina, arthritis, stroke, hypertension, asthma and diabetes and cytokines (Interleukins-1 and -6, C-Reactive Protein and Tumor Necrosis Factor-alpha by HIV and ART status on a cross-sectional random sample of 422 older adults nested within a defined rural South African population based demographic surveillance.Using a composite measure of all morbidities, controlling for age, gender, BMI, smoking and wealth quintile, HIV-infected individuals on ART had 51% decreased odds (95% CI:0.26-0.92 of current morbidity compared to HIV-uninfected. In adjusted regression, compared to HIV-uninfected, the proportional odds (aPOR of having elevated inflammation markers of IL6 (>1.56 pg/mL was nearly doubled in HIV-infected individuals on (aPOR 1.84; 95%CI: 1.05-3.21 and not on (aPOR 1.94; 95%CI: 1.11-3.41 ART. Compared to HIV-uninfected, HIV-infected individuals on ART had >twice partial proportional odds (apPOR=2.30;p=0.004 of having non-clinically significant raised hsCRP levels(>1 ug/mL; ART-naïve HIV-infected individuals had >double apPOR of having hsCRP levels indicative of increased heart disease risk(>3.9 ug/mL;p=0.008.Although HIV status was associated with increased inflammatory markers, our results highlight reduced morbidity in those receiving ART and underscore the need of pro-actively extending these services to HIV-uninfected older adults, beyond mere provision at fixed clinics. Providing health services through regular community chronic disease

  2. Distribution of short block copolymer chains in Binary Blends of Block Copolymers Having Hydrogen Bonding

    Science.gov (United States)

    Kwak, Jongheon; Han, Sunghyun; Kim, Jin Kon

    2014-03-01

    A binary mixture of two block copolymers whose blocks are capable of forming the hydrogen bonding allows one to obtain various microdomains that could not be expected for neat block copolymer. For instance, the binary blend of symmetric polystyrene-block-poly(2-vinylpyridine) copolymer (PS-b-P2VP) and polystyrene-block-polyhydroxystyrene copolymer (PS-b-PHS) blends where the hydrogen bonding occurred between P2VP and PHS showed hexagonally packed (HEX) cylindrical and body centered cubic (BCC) spherical microdomains. To know the exact location of short block copolymer chains at the interface, we synthesized deuterated polystyrene-block-polyhydroxystyrene copolymer (dPS-b-PHS) and prepared a binary mixture with PS-b-P2VP. We investigate, via small angle X-ray scattering (SAXS) and neutron reflectivity (NR), the exact location of shorter dPS block chain near the interface of the microdomains.

  3. Minimum Description Length Block Finder, a Method to Identify Haplotype Blocks and to Compare the Strength of Block Boundaries

    OpenAIRE

    Mannila, H.; Koivisto, M.; Perola, M.; Varilo, T.; Hennah, W.; Ekelund, J.; Lukk, M.; Peltonen, L.; Ukkonen, E.

    2003-01-01

    We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the ...

  4. The HIV Prison Paradox: Agency and HIV-Positive Women's Experiences in Jail and Prison in Alabama.

    Science.gov (United States)

    Sprague, Courtenay; Scanlon, Michael L; Radhakrishnan, Bharathi; Pantalone, David W

    2017-08-01

    Incarcerated women face significant barriers to achieve continuous HIV care. We employed a descriptive, exploratory design using qualitative methods and the theoretical construct of agency to investigate participants' self-reported experiences accessing HIV services in jail, in prison, and post-release in two Alabama cities. During January 2014, we conducted in-depth interviews with 25 formerly incarcerated HIV-positive women. Two researchers completed independent coding, producing preliminary codes from transcripts using content analysis. Themes were developed iteratively, verified, and refined. They encompassed (a) special rules for HIV-positive women: isolation, segregation, insults, food rationing, and forced disclosure; (b) absence of counseling following initial HIV diagnosis; and (c) HIV treatment impediments: delays, interruption, and denial. Participants deployed agentic strategies of accommodation, resistance, and care-seeking to navigate the social world of prison and HIV services. Findings illuminate the "HIV prison paradox": the chief opportunities that remain unexploited to engage and re-engage justice-involved women in the HIV care continuum.

  5. HIV-1 Vpu Blocks Recycling and Biosynthetic Transport of the Intrinsic Immunity Factor CD317/Tetherin To Overcome the Virion Release Restriction

    Science.gov (United States)

    Schmidt, Sarah; Fritz, Joëlle V.; Bitzegeio, Julia; Fackler, Oliver T.; Keppler, Oliver T.

    2011-01-01

    ABSTRACT The intrinsic immunity factor CD317 (BST-2/HM1.24/tetherin) imposes a barrier to HIV-1 release at the cell surface that can be overcome by the viral protein Vpu. Expression of Vpu results in a reduction of CD317 surface levels; however, the mechanism of this Vpu activity and its contribution to the virological antagonism are incompletely understood. Here, we characterized the influence of Vpu on major CD317 trafficking pathways using quantitative antibody-based endocytosis and recycling assays as well as a microinjection/microscopy-based kinetic de novo expression approach. We report that HIV-1 Vpu inhibited both the anterograde transport of newly synthesized CD317 and the recycling of CD317 to the cell surface, while the kinetics of CD317 endocytosis remained unaffected. Vpu trapped trafficking CD317 molecules at the trans-Golgi network, where the two molecules colocalized. The subversion of both CD317 transport pathways was dependent on the highly conserved diserine S52/S56 motif of Vpu; however, it did not require recruitment of the diserine motif interactor and substrate adaptor of the SCF-E3 ubiquitin ligase complex, β-TrCP. Treatment of cells with the malaria drug primaquine resulted in a CD317 trafficking defect that mirrored that induced by Vpu. Importantly, primaquine could functionally replace Vpu as a CD317 antagonist and rescue HIV-1 particle release. PMID:21610122

  6. Development and Validation of an HIV Risk Exposure and Indicator Conditions Questionnaire to Support Targeted HIV Screening.

    Science.gov (United States)

    Elías, María Jesús Pérez; Gómez-Ayerbe, Cristina; Elías, Pilar Pérez; Muriel, Alfonso; de Santiago, Alberto Diaz; Martinez-Colubi, María; Moreno, Ana; Santos, Cristina; Polo, Lidia; Barea, Rafa; Robledillo, Gema; Uranga, Almudena; Espín, Agustina Cano; Quereda, Carmen; Dronda, Fernando; Casado, Jose Luis; Moreno, Santiago

    2016-02-01

    The aim of our study was to develop a Spanish-structured HIV risk of exposure and indicator conditions (RE&IC) questionnaire. People attending to an emergency room or to a primary clinical care center were offered to participate in a prospective, 1 arm, open label study, in which all enrolled patients filled out our developed questionnaire and were HIV tested. Questionnaire accuracy, feasibility, and reliability were evaluated.Valid paired 5329 HIV RE&IC questionnaire and rapid HIV tests were performed, 69.3% in the primary clinical care center, 49.6% women, median age 37 years old, 74.9% Spaniards, 20.1% Latin-Americans. Confirmed hidden HIV infection was detected in 4.1%, while HIV RE&IC questionnaire was positive in 51.2%. HIV RE&IC questionnaire sensitivity was 100% to predict HIV infection, with a 100% negative predictive value. When considered separately, RE or IC items sensitivity decreases to 86.4% or 91%, and similarly their negative predictive value to 99.9% for both of them. The majority of people studied, 90.8% self-completed HIV RE&IC questionnaire. Median time to complete was 3 minutes. Overall HIV RE&IC questionnaire test-retest Kappa agreement was 0.82 (almost perfect), likewise for IC items 0.89, while for RE items was lower 0.78 (substantial).A feasible and reliable Spanish HIV RE&IC self questionnaire accurately discriminated all non-HIV-infected people without missing any HIV diagnoses, in a low prevalence HIV infection area. The best accuracy and reliability were obtained when combining HIV RE&IC items.

  7. Association of HIV diversity and survival in HIV-infected Ugandan infants.

    Directory of Open Access Journals (Sweden)

    Maria M James

    2011-04-01

    Full Text Available The level of viral diversity in an HIV-infected individual can change during the course of HIV infection, reflecting mutagenesis during viral replication and selection of viral variants by immune and other selective pressures. Differences in the level of viral diversity in HIV-infected infants may reflect differences in viral dynamics, immune responses, or other factors that may also influence HIV disease progression. We used a novel high resolution melting (HRM assay to measure HIV diversity in Ugandan infants and examined the relationship between diversity and survival through 5 years of age.Plasma samples were obtained from 31 HIV-infected infants (HIVNET 012 trial. The HRM assay was used to measure diversity in two regions in the gag gene (Gag1 and Gag2 and one region in the pol gene (Pol.HRM scores in all three regions increased with age from 6-8 weeks to 12-18 months (for Gag1: P = 0.005; for Gag2: P = 0.006; for Pol: P = 0.016. Higher HRM scores at 6-8 weeks of age (scores above the 75(th percentile were associated with an increased risk of death by 5 years of age (for Pol: P = 0.005; for Gag1/Gag2 (mean of two scores: P = 0.003; for Gag1/Gag2/Pol (mean of three scores: P = 0.002. We did not find an association between HRM scores and other clinical and laboratory variables.Genetic diversity in HIV gag and pol measured using the HRM assay was typically low near birth and increased over time. Higher HIV diversity in these regions at 6-8 weeks of age was associated with a significantly increased risk of death by 5 years of age.

  8. HIV-related stigma in pregnancy and early postpartum of mothers living with HIV in Ontario, Canada.

    Science.gov (United States)

    Ion, Allyson; Wagner, Anne C; Greene, Saara; Loutfy, Mona R

    2017-02-01

    HIV-related stigma is associated with many psychological challenges; however, minimal research has explored how perceived HIV-related stigma intersects with psychosocial issues that mothers living with HIV may experience including depression, perceived stress and social isolation. The present study aims to describe the correlates and predictors of HIV-related stigma in a cohort of women living with HIV (WLWH) from across Ontario, Canada during pregnancy and early postpartum. From March 2011 to December 2012, WLWH ≥ 18 years (n = 77) completed a study instrument measuring independent variables including sociodemographic characteristics, perceived stress, depression symptoms, social isolation, social support and perceived racism in the third trimester and 3, 6 and 12 months postpartum. Multivariable linear regression was employed to explore the relationship between HIV-related stigma and multiple independent variables. HIV-related stigma generally increased from pregnancy to postpartum; however, there were no significant differences in HIV-related stigma across all study time points. In multivariable regression, depression symptoms and perceived racism were significant predictors of overall HIV-related stigma from pregnancy to postpartum. The present analysis contributes to our understanding of HIV-related stigma throughout the pregnancy-motherhood trajectory for WLWH including the interactional relationship between HIV-related stigma and other psychosocial variables, most notably, depression and racism.

  9. Impulsivity, Sensation Seeking, and Risk-Taking Behaviors among HIV-Positive and HIV-Negative Heroin Dependent Persons

    Directory of Open Access Journals (Sweden)

    Koosha Paydary

    2016-01-01

    Full Text Available Objective. The aim of this study was to compare impulsivity and risky decision making among HIV-positive and negative heroin dependent persons. Methods. We compared different dimensions of impulsivity and risky decision making in two groups of 60 HIV-positive and 60 HIV-negative male heroin dependent persons. Each group was comprised of equal numbers of current (treatment seeker and former (abstinent heroin addicts. Data collection tools included Balloon Analogue Risk Task (BART, Iowa Gambling Task (IGT, Barratt Impulsiveness Scale (BIS, and Zuckerman Sensation Seeking Scale (SSS. Results. In SSS, comprised of four subscales including thrill and adventure seeking (TAS, experience seeking (ES, disinhibition (DIS, and boredom susceptibility (BS, there was a borderline difference in DIS (P=0.08 as HIV-positive group scored higher than HIV-negative group. Also, ES and total score were significantly higher among HIV-positive patients. In BART, HIV-positive subjects scored higher in risk taking than HIV-negative subjects as reflected in higher Average Number of puffs in Successful Balloons (ANSB. In BIS, HIV-positive group scored significantly higher in cognitive impulsivity (CI (P=0.03 and nonplanning impulsivity (NPI (P=0.05 in comparison to HIV-negative group. Also, current heroin addicts scored significantly higher in NPI compared to former addict HIV-negative participants (P=0.015. IGT did not show any significant difference between groups. Conclusion. Higher levels of impulsivity and risk taking behaviors among HIV-positive heroin addicts will increase serious concerns regarding HIV transmission from this group to other opiate dependents and healthy people.

  10. Impulsivity, Sensation Seeking, and Risk-Taking Behaviors among HIV-Positive and HIV-Negative Heroin Dependent Persons

    Science.gov (United States)

    Paydary, Koosha; Mahin Torabi, Somayeh; SeyedAlinaghi, SeyedAhmad; Noori, Mehri; Noroozi, Alireza; Ameri, Sara; Ekhtiari, Hamed

    2016-01-01

    Objective. The aim of this study was to compare impulsivity and risky decision making among HIV-positive and negative heroin dependent persons. Methods. We compared different dimensions of impulsivity and risky decision making in two groups of 60 HIV-positive and 60 HIV-negative male heroin dependent persons. Each group was comprised of equal numbers of current (treatment seeker) and former (abstinent) heroin addicts. Data collection tools included Balloon Analogue Risk Task (BART), Iowa Gambling Task (IGT), Barratt Impulsiveness Scale (BIS), and Zuckerman Sensation Seeking Scale (SSS). Results. In SSS, comprised of four subscales including thrill and adventure seeking (TAS), experience seeking (ES), disinhibition (DIS), and boredom susceptibility (BS), there was a borderline difference in DIS (P = 0.08) as HIV-positive group scored higher than HIV-negative group. Also, ES and total score were significantly higher among HIV-positive patients. In BART, HIV-positive subjects scored higher in risk taking than HIV-negative subjects as reflected in higher Average Number of puffs in Successful Balloons (ANSB). In BIS, HIV-positive group scored significantly higher in cognitive impulsivity (CI) (P = 0.03) and nonplanning impulsivity (NPI) (P = 0.05) in comparison to HIV-negative group. Also, current heroin addicts scored significantly higher in NPI compared to former addict HIV-negative participants (P = 0.015). IGT did not show any significant difference between groups. Conclusion. Higher levels of impulsivity and risk taking behaviors among HIV-positive heroin addicts will increase serious concerns regarding HIV transmission from this group to other opiate dependents and healthy people. PMID:27051528

  11. Late HIV Testing in a Cohort of HIV-Infected Patients in Puerto Rico.

    Science.gov (United States)

    Tossas-Milligan, Katherine Y; Hunter-Mellado, Robert F; Mayor, Angel M; Fernández-Santos, Diana M; Dworkin, Mark S

    2015-09-01

    Late HIV testing (LT), defined as receiving an AIDS diagnosis within a year of one's first positive HIV test, is associated with higher HIV transmission, lower HAART effectiveness, and worse outcomes. Latinos represent 36% of LT in the US, yet research concerning LT among HIV cases in Puerto Rico is scarce. Multivariable logistic regression analysis was used to identify factors associated with LT, and a Cochran‒Armitage test was used to determine LT trends in an HIV-infected cohort followed at a clinic in Puerto Rico specialized in the management and treatment of HIV. From 2000 to 2011, 47% of eligible patients were late testers, with lower median CD4 counts (54 vs. 420 cells/mm3) and higher median HIV viral load counts (253,680 vs. 23,700 copies/mL) than non-LT patients. LT prevalence decreased significantly, from 47% in 2000 to 37% in 2011. In a mutually adjusted logistic regression model, males, older age at enrollment and past history of IDU significantly increased LT odds, whereas having a history of amphetamine use decreased LT odds. When the data were stratified by mode of transmission, it became apparent that only the category men who have sex with men (MSM) saw a significant reduction in the proportion of LT, falling from 67% in 2000 to 33% in 2011. These results suggest a gap in early HIV detection in Puerto Rico, a gap that decreased only among MSM. An evaluation of the manner in which current HIV-testing guidelines are implemented on the island is needed.

  12. Experiences of HIV-related stigma among HIV-positive older ...

    African Journals Online (AJOL)

    Monica O. Kuteesa

    2014-07-23

    Jul 23, 2014 ... SAHARA-J: Journal of Social Aspects of HIV/AIDS: An .... (rural site) and Wakiso district (peri-urban site) residents, we measured self-reported stigma levels for 183 .... HIV stigma has been defined as 'prejudice, discounting, discredit- ... inadequate support networks, isolation loneliness and depression.

  13. Nosocomial infections in HIV-infected and HIV-uninfected children ...

    African Journals Online (AJOL)

    The interaction between tuberculosis and HIV-infected infection is well known and is responsible for the increase in the incidence of tuberculosis ... This retrospective case-control study evaluated the occurrence of nosocomial infections in (HIV)-infected children and age- and time of ... complicated disease, or whose social.

  14. Fracture risk by HIV infection status in perinatally HIV-exposed children.

    Science.gov (United States)

    Siberry, George K; Li, Hong; Jacobson, Denise

    2012-03-01

    The objective of this study was to examine the incidence of fractures in HIV-infected children and comparable HIV-exposed, uninfected (HEU) children in a multicenter, prospective cohort study (PACTG 219/219C) in the United States. The main outcome was first fracture during the risk period. Nine fractures occurred in 7 of 1326 HIV-infected and 2 of 649 HEU children, corresponding to incidence rates of 1.2 per 1000 person-years and 1.1 per 1000 person-years, respectively. The incidence rate ratio was 1.1 (95% CI 0.2, 5.5). There was no evidence of a substantially increased risk of fracture in HIV-infected compared to HEU children.

  15. Use of surveillance data on HIV diagnoses with HIV-related symptoms to estimate the number of people living with undiagnosed HIV in need of antiretroviral therapy.

    Science.gov (United States)

    Lodwick, Rebecca K; Nakagawa, Fumiyo; van Sighem, Ard; Sabin, Caroline A; Phillips, Andrew N

    2015-01-01

    It is important to have methods available to estimate the number of people who have undiagnosed HIV and are in need of antiretroviral therapy (ART). The method uses the concept that a predictable level of occurrence of AIDS or other HIV-related clinical symptoms which lead to presentation for care, and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count. The method requires surveillance data on numbers of new HIV diagnoses with HIV-related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at which HIV-related symptoms develop are estimated from cohort data. 95% confidence intervals can be constructed using a simple simulation method. For example, if there were 13 HIV diagnoses with HIV-related symptoms made in one year with CD4 count at diagnosis between 150-199 cells/mm3, then since the CD4 count-specific rate of HIV-related symptoms is estimated as 0.216 per person-year, the estimated number of person years lived in people with undiagnosed HIV with CD4 count 150-199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29-100), which is considered an estimate of the number of people living with undiagnosed HIV in this CD4 count stratum. The method is straightforward to implement within a short period once a surveillance system of all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is in place and is most suitable for estimating the number of undiagnosed people with CD4 count HIV-related symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and under-reporting of diagnoses with HIV-related symptoms. Although this method has limitations as with all approaches, it is important for prompting increased efforts to identify undiagnosed people, particularly those with low CD4 count, and for informing levels of unmet need for ART.

  16. Developing strategies for HIV-1 eradication

    Science.gov (United States)

    Durand, Christine M.; Blankson, Joel N.; Siliciano, Robert F.

    2014-01-01

    Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication, transforming the outlook for infected patients. However, reservoirs of replication-competent forms of the virus persist during HAART, and when treatment is stopped, high rates of HIV-1 replication return. Recent insights into HIV-1 latency, as well as a report that HIV-1 infection was eradicated in one individual, have renewed interest in finding a cure for HIV-1 infection. Strategies for HIV-1 eradication include gene therapy and hematopoietic stem cell transplantation, stimulating host immunity to control HIV-1 replication, and targeting latent HIV-1 in resting memory CD4+ T cells. Future efforts should aim to provide better understanding of how to reconstitute the CD4+ T cell compartment with genetically engineered cells, exert immune control over HIV-1 replication, and identify and eliminate all viral reservoirs. PMID:22867874

  17. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men.

    Science.gov (United States)

    Korhonen, Christine J; Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L; Sanders, Eduard J; Peshu, Norbert M; Krieger, John N; Muller, Charles H; Coombs, Robert W; Fredricks, David N; Graham, Susan M

    2017-03-01

    HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.

  18. Fotodegradovatelné inhibitory HIV proteasy

    Czech Academy of Sciences Publication Activity Database

    Schimer, Jiří; Pávová, Marcela; Prouzová, Hana; Weber, Jan; Cígler, Petr; Majer, Pavel; Konvalinka, Jan

    2014-01-01

    Roč. 108, č. 5 (2014), s. 549 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků /14./. 13.05.2014-16.05.2014, Milovy] Institutional support: RVO:61388963 Keywords : HIV protease * HIV PR inhibitors * Caged HIV Pr * HIV maturation Subject RIV: CE - Biochemistry

  19. National HIV Testing Day at CDC-funded HIV counseling, testing, and referral sites--United States, 1994-1998.

    Science.gov (United States)

    2000-06-23

    CDC-funded human immunodeficiency virus (HIV) counseling, testing, and referral sites are an integral part of national HIV prevention efforts (1). Voluntary counseling, testing, and referral opportunities are offered to persons at risk for HIV infection at approximately 11,000 sites, including dedicated HIV counseling and testing sites, sexually transmitted disease (STD) clinics, drug-treatment centers, hospitals, and prisons. Services also are offered to women in family planning and prenatal/obstetric clinics to increase HIV prevention efforts among women and decrease the risk for perinatal HIV transmission. To increase use of HIV counseling, testing, and referral services by those at risk for HIV infection, in 1995, the National Association of People with AIDS designated June 27 each year as National HIV Testing Day. This report compares use of CDC-funded counseling, testing, and referral services the week before and the week of June 27 from 1994 through 1998 and documents the importance of a national public health campaign designed to increase knowledge of HIV serostatus.

  20. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

    Directory of Open Access Journals (Sweden)

    Chungen Pan

    2010-02-01

    Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.