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Sample records for hiv gp41 engages

  1. Membrane topology analysis of HIV-1 envelope glycoprotein gp41

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    Xiao Dan

    2010-11-01

    Full Text Available Abstract Background The gp41 subunit of the HIV-1 envelope glycoprotein (Env has been widely regarded as a type I transmembrane protein with a single membrane-spanning domain (MSD. An alternative topology model suggested multiple MSDs. The major discrepancy between the two models is that the cytoplasmic Kennedy sequence in the single MSD model is assigned as the extracellular loop accessible to neutralizing antibodies in the other model. We examined the membrane topology of the gp41 subunit in both prokaryotic and mammalian systems. We attached topological markers to the C-termini of serially truncated gp41. In the prokaryotic system, we utilized a green fluorescent protein (GFP that is only active in the cytoplasm. The tag protein (HaloTag and a membrane-impermeable ligand specific to HaloTag was used in the mammalian system. Results In the absence of membrane fusion, both the prokaryotic and mammalian systems (293FT cells supported the single MSD model. In the presence of membrane fusion in mammalian cells (293CD4 cells, the data obtained seem to support the multiple MSD model. However, the region predicted to be a potential MSD is the highly hydrophilic Kennedy sequence and is least likely to become a MSD based on several algorithms. Further analysis revealed the induction of membrane permeability during membrane fusion, allowing the membrane-impermeable ligand and antibodies to cross the membrane. Therefore, we cannot completely rule out the possible artifacts. Addition of membrane fusion inhibitors or alterations of the MSD sequence decreased the induction of membrane permeability. Conclusions It is likely that a single MSD model for HIV-1 gp41 holds true even in the presence of membrane fusion. The degree of the augmentation of membrane permeability we observed was dependent on the membrane fusion and sequence of the MSD.

  2. HIV-1 infection: functional competition between gp41 and interleukin-2.

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    Sanhadji, Kamel; Tardy, Jean-Claude; Touraine, Jean-Louis

    2010-08-01

    To determine whether the gp41 of HIV-1 could adhere to the interleukin (IL)-2 receptor at the surface of target cells in vitro, we analysed in vitro the possible functional competition between various forms of the HIV-1 gp41 molecule (i.e. peptides, trimeric or primary structures) and IL-2. This competition has been analysed in a test involving the proliferation of an IL-2-dependent cell line (CTLL2). The putative interaction between the IL-2 molecule and HIV-1 has also been assayed on MT4 cells (CD4(+) T lymphocytes) in culture. The gp41 trimeric molecule and an HIV-1 gp41 peptide (578-590 aminoacid sequence) dramatically inhibited CTLL2 cell proliferation, despite the presence of IL-2. The addition of serum, containing anti-gp41 antibodies, from HIV-1 patients resulted in a significant abolition of this inhibition. The concomitant incubation of IL-2 and HIV-1 with MT4 cells resulted in a strong decrease (70%) in HIV-1 p24 release. These data suggest that the gp41 of HIV-1 can use the IL-2 receptor during the process of HIV-1 infection and that there is some functional mimesis between gp41 and IL-2. Copyright 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  3. Residues in the gp41 Ectodomain Regulate HIV-1 Envelope Glycoprotein Conformational Transitions Induced by gp120-Directed Inhibitors.

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    Pacheco, Beatriz; Alsahafi, Nirmin; Debbeche, Olfa; Prévost, Jérémie; Ding, Shilei; Chapleau, Jean-Philippe; Herschhorn, Alon; Madani, Navid; Princiotto, Amy; Melillo, Bruno; Gu, Christopher; Zeng, Xin; Mao, Youdong; Smith, Amos B; Sodroski, Joseph; Finzi, Andrés

    2017-03-01

    Interactions between the gp120 and gp41 subunits of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer maintain the metastable unliganded form of the viral spike. Binding of gp120 to the receptor, CD4, changes the Env conformation to promote gp120 interaction with the second receptor, CCR5 or CXCR4. CD4 binding also induces the transformation of Env into the prehairpin intermediate, in which the gp41 heptad repeat 1 (HR1) coiled coil is assembled at the trimer axis. In nature, HIV-1 Envs must balance the requirements to maintain the noncovalent association of gp120 with gp41 and to evade the host antibody response with the need to respond to CD4 binding. Here we show that the gp41 HR1 region contributes to gp120 association with the unliganded Env trimer. Changes in particular amino acid residues in the gp41 HR1 region decreased the efficiency with which Env moved from the unliganded state. Thus, these gp41 changes decreased the sensitivity of HIV-1 to cold inactivation and ligands that require Env conformational changes to bind efficiently. Conversely, these gp41 changes increased HIV-1 sensitivity to small-molecule entry inhibitors that block Env conformational changes induced by CD4. Changes in particular gp41 HR1 amino acid residues can apparently affect the relative stability of the unliganded state and CD4-induced conformations. Thus, the gp41 HR1 region contributes to the association with gp120 and regulates Env transitions from the unliganded state to downstream conformations.IMPORTANCE The development of an efficient vaccine able to prevent HIV infection is a worldwide priority. Knowledge of the envelope glycoprotein structure and the conformational changes that occur after receptor engagement will help researchers to develop an immunogen able to elicit antibodies that block HIV-1 transmission. Here we identify residues in the HIV-1 transmembrane envelope glycoprotein that stabilize the unliganded state by modulating the

  4. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

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    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.

  5. HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques.

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    Han, Qifeng; Williams, Wilton B; Saunders, Kevin O; Seaton, Kelly E; Wiehe, Kevin J; Vandergrift, Nathan; Von Holle, Tarra A; Trama, Ashley M; Parks, Robert J; Luo, Kan; Gurley, Thaddeus C; Kepler, Thomas B; Marshall, Dawn J; Montefiori, David C; Sutherland, Laura L; Alam, Munir S; Whitesides, John F; Bowman, Cindy M; Permar, Sallie R; Graham, Barney S; Mascola, John R; Seed, Patrick C; Van Rompay, Koen K A; Tomaras, Georgia D; Moody, M Anthony; Haynes, Barton F

    2017-11-01

    Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41-reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.IMPORTANCE Our results are critical to current work in the HIV-1 vaccine field evaluating the phenomenon of gp41 immunodominance induced by HIV-1 Env gp140 in RMs and humans. Our data demonstrate that RMs are an appropriate animal model to study this phenomenon and to determine the immunogenicity in new HIV-1 Env trimer vaccine designs. The demonstration of gp41 immunodominance in

  6. Asymmetric deactivation of HIV-1 gp41 following fusion inhibitor binding.

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    Kristen M Kahle

    2009-11-01

    Full Text Available Both equilibrium and nonequilibrium factors influence the efficacy of pharmaceutical agents that target intermediate states of biochemical reactions. We explored the intermediate state inhibition of gp41, part of the HIV-1 envelope glycoprotein complex (Env that promotes viral entry through membrane fusion. This process involves a series of gp41 conformational changes coordinated by Env interactions with cellular CD4 and a chemokine receptor. In a kinetic window between CD4 binding and membrane fusion, the N- and C-terminal regions of the gp41 ectodomain become transiently susceptible to inhibitors that disrupt Env structural transitions. In this study, we sought to identify kinetic parameters that influence the antiviral potency of two such gp41 inhibitors, C37 and 5-Helix. Employing a series of C37 and 5-Helix variants, we investigated the physical properties of gp41 inhibition, including the ability of inhibitor-bound gp41 to recover its fusion activity once inhibitor was removed from solution. Our results indicated that antiviral activity critically depended upon irreversible deactivation of inhibitor-bound gp41. For C37, which targets the N-terminal region of the gp41 ectodomain, deactivation was a slow process that depended on chemokine receptor binding to Env. For 5-Helix, which targets the C-terminal region of the gp41 ectodomain, deactivation occurred rapidly following inhibitor binding and was independent of chemokine receptor levels. Due to this kinetic disparity, C37 inhibition was largely reversible, while 5-Helix inhibition was functionally irreversible. The fundamental difference in deactivation mechanism points to an unappreciated asymmetry in gp41 following inhibitor binding and impacts the development of improved fusion inhibitors and HIV-1 vaccines. The results also demonstrate how the activities of intermediate state inhibitors critically depend upon the final disposition of inhibitor-bound states.

  7. Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization.

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    Arthur S Kim

    2014-07-01

    Full Text Available Human antibody 10E8 targets the conserved membrane proximal external region (MPER of envelope glycoprotein (Env subunit gp41 and neutralizes HIV-1 with exceptional potency. Remarkably, HIV-1 containing mutations that reportedly knockout 10E8 binding to linear MPER peptides are partially neutralized by 10E8, producing a local plateau in the dose response curve. Here, we found that virus partially neutralized by 10E8 becomes significantly less neutralization sensitive to various MPER antibodies and to soluble CD4 while becoming significantly more sensitive to antibodies and fusion inhibitors against the heptad repeats of gp41. Thus, 10E8 modulates sensitivity of Env to ligands both pre- and post-receptor engagement without complete neutralization. Partial neutralization by 10E8 was influenced at least in part by perturbing Env glycosylation. With unliganded Env, 10E8 bound with lower apparent affinity and lower subunit occupancy to MPER mutant compared to wild type trimers. However, 10E8 decreased functional stability of wild type Env while it had an opposite, stabilizing effect on MPER mutant Envs. Clade C isolates with natural MPER polymorphisms also showed partial neutralization by 10E8 with altered sensitivity to various gp41-targeted ligands. Our findings suggest a novel mechanism of virus neutralization by demonstrating how antibody binding to the base of a trimeric spike cross talks with adjacent subunits to modulate Env structure and function. The ability of an antibody to stabilize, destabilize, partially neutralize as well as alter neutralization sensitivity of a virion spike pre- and post-receptor engagement may have implications for immunotherapy and vaccine design.

  8. Antigenic and immunosuppressive properties of a trimeric recombinant transmembrane envelope protein gp41 of HIV-1.

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    Michael Mühle

    Full Text Available The transmembrane envelope (TM protein gp41 of the human immunodeficiency virus-1 (HIV-1 plays an important role during virus infection inducing the fusion of the viral and cellular membranes. In addition, there are indications that the TM protein plays a role in the immunopathogenesis leading to the acquired immunodeficiency syndrome (AIDS. Inactivated virus particles and recombinant gp41 have been reported to inhibit lymphocyte proliferation, as well as to alter cytokine release and gene expression. The same was shown for a peptide corresponding to a highly conserved domain of all retroviral TM proteins, the immunosuppressive domain. Due to its propensity to aggregate and to be expressed at low levels, studies comprising authentic gp41 produced in eukaryotic cells are extremely rare. Here we describe the production of a secreted, soluble recombinant gp41 in 293 cells. The antigen was purified to homogeneity and characterised thoroughly by various biochemical and immunological methods. It was shown that the protein was glycosylated and assembled into trimers. Binding studies by ELISA and surface plasmon resonance using conformation-specific monoclonal antibodies implied a six-helix bundle conformation. The low binding of broadly neutralising antibodies (bnAb directed against the membrane proximal external region (MPER suggested that this gp41 is probably not suited as vaccine to induce such bnAb. Purified gp41 bound to monocytes and to a lesser extent to lymphocytes and triggered the production of specific cytokines when added to normal peripheral blood mononuclear cells. In addition, gp41 expressed on target cells inhibited the antigen-specific response of murine CD8+ T cells by drastically impairing their IFNγ production. To our knowledge, this is the first comprehensive analysis of a gp41 produced in eukaryotic cells including its immunosuppressive properties. Our data provide another line of evidence that gp41 might be directly involved in

  9. Diversion of HIV-1 Vaccine-induced Immunity by gp41-Microbiota Cross-reactive Antibodies

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    Williams, Wilton B; Liao, Hua-Xin; Moody, M. Anthony; Kepler, Thomas B.; Alam, S Munir; Gao, Feng; Wiehe, Kevin; Trama, Ashley M.; Jones, Kathryn; Zhang, Ruijun; Song, Hongshuo; Marshall, Dawn J; Whitesides, John F; Sawatzki, Kaitlin; Hua, Axin; Liu, Pinghuang; Tay, Matthew Z; Seaton, Kelly; Shen, Xiaoying; Foulger, Andrew; Lloyd, Krissey E.; Parks, Robert; Pollara, Justin; Ferrari, Guido; Yu, Jae-Sung; Vandergrift, Nathan; Montefiori, David C.; Sobieszczyk, Magdalena E; Hammer, Scott; Karuna, Shelly; Gilbert, Peter; Grove, Doug; Grunenberg, Nicole; McElrath, Julie; Mascola, John R.; Koup, Richard A; Corey, Lawrence; Nabel, Gary J.; Morgan, Cecilia; Churchyard, Gavin; Maenza, Janine; Keefer, Michael; Graham, Barney S.; Baden, Lindsey R.; Tomaras, Georgia D.; Haynes, Barton F.

    2015-01-01

    A HIV-1 DNA prime-recombinant Adenovirus Type 5 (rAd5) boost vaccine failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells was to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies (mAbs) were non-neutralizing, and frequently polyreactive with host and environmental antigens including intestinal microbiota (IM). Next generation sequencing of an IGHV repertoire prior to vaccination revealed an Env-IM cross-reactive Ab that was clonally-related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy. PMID:26229114

  10. Approaches for Identification of HIV-1 Entry Inhibitors Targeting gp41 Pocket

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    Asim K. Debnath

    2013-01-01

    Full Text Available The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon, was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD, it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs.

  11. Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated

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    Chen, Xi; Munshaw, Supriya; Zhang, Ruijun; Marshall, Dawn J.; Vandergrift, Nathan; Whitesides, John F.; Lu, Xiaozhi; Yu, Jae-Sung; Hwang, Kwan-Ki; Gao, Feng; Markowitz, Martin; Heath, Sonya L.; Bar, Katharine J.; Goepfert, Paul A.; Montefiori, David C.; Shaw, George C.; Alam, S. Munir; Margolis, David M.; Denny, Thomas N.; Boyd, Scott D.; Marshal, Eleanor; Egholm, Michael; Simen, Birgitte B.; Hanczaruk, Bozena; Fire, Andrew Z.; Voss, Gerald; Kelsoe, Garnett; Tomaras, Georgia D.; Moody, M. Anthony; Kepler, Thomas B.

    2011-01-01

    The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non–HIV-1 antigens. PMID:21987658

  12. HIV gp41 engages gC1qR on CD4+ T cells to induce the expression of an NK ligand through the PIP3/H2O2 pathway.

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    Hugues Fausther-Bovendo

    Full Text Available CD4(+ T cell loss is central to HIV pathogenesis. In the initial weeks post-infection, the great majority of dying cells are uninfected CD4(+ T cells. We previously showed that the 3S motif of HIV-1 gp41 induces surface expression of NKp44L, a cellular ligand for an activating NK receptor, on uninfected bystander CD4(+ T cells, rendering them susceptible to autologous NK killing. However, the mechanism of the 3S mediated NKp44L surface expression on CD4(+ T cells remains unknown. Here, using immunoprecipitation, ELISA and blocking antibodies, we demonstrate that the 3S motif of HIV-1 gp41 binds to gC1qR on CD4(+ T cells. We also show that the 3S peptide and two endogenous gC1qR ligands, C1q and HK, each trigger the translocation of pre-existing NKp44L molecules through a signaling cascade that involves sequential activation of PI3K, NADPH oxidase and p190 RhoGAP, and TC10 inactivation. The involvement of PI3K and NADPH oxidase derives from 2D PAGE experiments and the use of PIP3 and H2O2 as well as small molecule inhibitors to respectively induce and inhibit NKp44L surface expression. Using plasmid encoding wild type or mutated form of p190 RhoGAP, we show that 3S mediated NKp44L surface expression on CD4(+ T cells is dependent on p190 RhoGAP. Finally, the role of TC10 in NKp44L surface induction was demonstrated by measuring Rho protein activity following 3S stimulation and using RNA interference. Thus, our results identify gC1qR as a new receptor of HIV-gp41 and demonstrate the signaling cascade it triggers. These findings identify potential mechanisms that new therapeutic strategies could use to prevent the CD4(+ T cell depletion during HIV infection and provide further evidence of a detrimental role played by NK cells in CD4(+ T cell depletion during HIV-1 infection.

  13. Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike

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    Lee, Jeong Hyun; Leaman, Daniel P.; Kim, Arthur S.; Torrents de La Peña, Alba; Sliepen, Kwinten; Yasmeen, Anila; Derking, Ronald; Ramos, Alejandra; de Taeye, Steven W.; Ozorowski, Gabriel; Klein, Florian; Burton, Dennis R.; Nussenzweig, Michel C.; Poignard, Pascal; Moore, John P.; Klasse, Per Johan; Sanders, Rogier W.; Zwick, Michael B.; Wilson, Ian A.; Ward, Andrew B.

    2015-09-01

    The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120-gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.

  14. HIV-1 Fusion Is Blocked through Binding of GB Virus C E2D Peptides to the HIV-1 gp41 Disulfide Loop

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    Eissmann, Kristin; Mueller, Sebastian; Sticht, Heinrich; Jung, Susan; Zou, Peng; Jiang, Shibo; Gross, Andrea; Eichler, Jutta; Fleckenstein, Bernhard; Reil, Heide

    2013-01-01

    A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms. HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C), since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments. GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells. Therefore, GBV-C shares partly the same ecological niche with HIV-1. In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry. In this study we investigated the underlying mechanism. Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor. Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41. In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120. This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface. Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors. PMID:23349893

  15. HIV-1 fusion is blocked through binding of GB Virus C E2-derived peptides to the HIV-1 gp41 disulfide loop [corrected].

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    Kristin Eissmann

    Full Text Available A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms. HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C, since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments. GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells. Therefore, GBV-C shares partly the same ecological niche with HIV-1. In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry. In this study we investigated the underlying mechanism. Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor. Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41. In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120. This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface. Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors.

  16. Small-molecule HIV-1 entry inhibitors targeting gp120 and gp41: a patent review (2010-2015).

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    Li, Wen; Lu, Lu; Li, Weihua; Jiang, Shibo

    2017-06-01

    It is essential to discover and develop small-molecule HIV-1 entry inhibitors with suitable pharmaceutical properties. Areas covered: We review the development of small-molecule HIV-1 entry inhibitors as evidenced in patents, patent applications, and related research articles published between 2010 and 2015. Expert opinion: HIV-1 Env gp120 and gp41 are important targets for development of HIV-1 entry inhibitors. The Phe43 pocket in gp120 and the highly conserved hydrophobic pocket on gp41 NHR-trimer are important targets for identification of HIV-1 attachment and fusion inhibitors, respectively. Compounds that bind to Phe43 pocket can block viral gp120 binding to CD4 on T cells, thus inhibiting HIV-1 attachment. However, most compounds targeting Phe43 pocket identified so far are HIV-1 entry agonists with the ability to enhance infectivity of HIV-1 in CD4-negative cells. Therefore, it is essential to identify HIV-1 entry antagonist-based HIV-1 attachment/entry inhibitors. Compounds binding to the gp41 hydrophobic pocket may inhibit CHR binding to the gp41 NHR trimer, thus blocking six-helix bundle formation and gp41-mediated virus-cell fusion. However, most lead compounds targeting this pocket have low potency, possibly because the pocket is too big or too deep. Therefore, it is necessary to identify other pockets in gp41 for developing HIV-1 fusion/entry inhibitors.

  17. Solution Structure and Membrane Interaction of the Cytoplasmic Tail of HIV-1 gp41 Protein.

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    Murphy, R Elliot; Samal, Alexandra B; Vlach, Jiri; Saad, Jamil S

    2017-11-07

    The cytoplasmic tail of gp41 (gp41CT) remains the last HIV-1 domain with an unknown structure. It plays important roles in HIV-1 replication such as mediating envelope (Env) intracellular trafficking and incorporation into assembling virions, mechanisms of which are poorly understood. Here, we present the solution structure of gp41CT in a micellar environment and characterize its interaction with the membrane. We show that the N-terminal 45 residues are unstructured and not associated with the membrane. However, the C-terminal 105 residues form three membrane-bound amphipathic α helices with distinctive structural features such as variable degree of membrane penetration, hydrophobic and basic surfaces, clusters of aromatic residues, and a network of cation-π interactions. This work fills a major gap by providing the structure of the last segment of HIV-1 Env, which will provide insights into the mechanisms of Gag-mediated Env incorporation as well as the overall Env mobility and conformation on the virion surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. A monocyte chemotaxis inhibiting factor in serum of HIV infected men shares epitopes with the HIV transmembrane protein gp41

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    Tas, M.; Drexhage, H. A.; Goudsmit, J.

    1988-01-01

    This report describes that gp41, the transmembranous envelope protein of HIV, is able to inhibit monocyte chemotaxis (measured as FMLP-induced polarization). To study the presence of such immunosuppressive HIV env proteins in the circulation of HIV-infected men, fractions were prepared from serum

  19. Evaluation of "credit card" libraries for inhibition of HIV-1 gp41 fusogenic core formation.

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    Xu, Yang; Lu, Hong; Kennedy, Jack P; Yan, Xuxia; McAllister, Laura A; Yamamoto, Noboru; Moss, Jason A; Boldt, Grant E; Jiang, Shibo; Janda, Kim D

    2006-01-01

    Protein-protein interactions are of critical importance in biological systems, and small molecule modulators of such protein recognition and intervention processes are of particular interest. To investigate this area of research, we have synthesized small-molecule libraries that can disrupt a number of biologically relevant protein-protein interactions. These library members are designed upon planar motif, appended with a variety of chemical functions, which we have termed "credit-card" structures. From two of our "credit-card" libraries, a series of molecules were uncovered which act as inhibitors against the HIV-1 gp41 fusogenic 6-helix bundle core formation, viral antigen p24 formation, and cell-cell fusion at low micromolar concentrations. From the high-throughput screening assays we utilized, a selective index (SI) value of 4.2 was uncovered for compound 2261, which bodes well for future structure activity investigations and the design of more potent gp41 inhibitors.

  20. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

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    Roche, Julien; Louis, John M.; Aniana, Annie [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States); Ghirlando, Rodolfo [National Institutes of Health, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States)

    2015-04-15

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion.

  1. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity

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    Todd Bradley

    2016-10-01

    Full Text Available Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1 viruses or rare cases of vaccine-matched neutralization-resistant (tier-2 viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we isolated antibodies from an HIV-1-infected individual that targeted the gp41 membrane-proximal external region (MPER that may have selected single-residue changes in viral variants in the MPER that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change in the MPER in a second virus from another infected-individual also conferred enhanced neutralization sensitivity. These gp41 single-residue changes thus transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine-elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino acid changes within the MPER bnAb epitope of naturally-selected escape viruses can increase neutralization sensitivity to multiple types of neutralizing antibodies, and underscore the critical importance of the MPER for maintaining the integrity of the tier-2 HIV-1 trimer.

  2. Immunogenicity of a chimeric hepatitis A virus (HAV) carrying the HIV gp41 epitope 2F5.

    Science.gov (United States)

    Kusov, Yuri Y; Zamjatina, Natalja A; Poleschuk, Valentina F; Michailov, Michail I; Morace, Graziella; Eberle, Josef; Gauss-Müller, Verena

    2007-02-01

    Its stable particle structure combined with its high immunogenicity makes the hepatitis A virus (HAV) a perfect carrier to expose foreign epitopes to the host immune system. In an earlier report [Beneduce, F., Kusov, Y., Klinger, M., Gauss-Müller, V., Morace, G., 2002. Chimeric hepatitis A virus particles presenting a foreign epitope (HIV gp41) at their surface. Antiviral Res. 55, 369-377] chimeric virus-like particles (HAV-gp41) were described that carried at their surface the dominant gp41 epitope 2F5 (2F5e) of the human immunodeficiency virus HIV-1. Extending this work, we now report that chimeric virus HAV-gp41 replicates in HAV-susceptible cells as well as in non-human primates. Infected marmosets developed both an anti-HAV and anti-2F5 epitope immune response. Furthermore, an HIV-neutralizing antibody response was elicited in guinea pigs immunized with HAV-gp41 chimeric particles. The results demonstrate that the replication-competent chimeric HAV-gp41 can serve as either a live or a subunit vaccine for eliciting of antibodies directed against a foreign antigenic epitope.

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

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    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.

  4. Evaluation of sequence variability in HIV-1 gp41 C-peptide helix-grafted proteins.

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    Tennyson, Rachel L; Walker, Susanne N; Ikeda, Terumasa; Harris, Reuben S; McNaughton, Brian R

    2017-08-01

    Many therapeutically-relevant protein-protein interactions (PPIs) have been reported that feature a helix and helix-binding cleft at the interface. Given this, different approaches to disrupting such PPIs have been developed. While short peptides (<15 amino acids) typically do not fold into a stable helix, researchers have reported chemical approaches to constraining helix structure. However, these approaches rely on laborious, and often expensive, chemical synthesis and purification. Our premise is that protein-based solutions that stabilize a therapeutically-relevant helix offer a number of advantages. In contrast to chemically constrained helical peptides, or minimal/miniature proteins, which must be synthesized (at great expense and labor), a protein can be expressed in a cellular system (like all current protein therapeutics). If selected properly, the protein scaffold can stabilize the therapeutically-relevant helix. We recently reported a protein engineering strategy, which we call "helix-grafted display", and applied it to the challenge of suppressing HIV entry. We have reported helix-grafted display proteins that inhibit formation of an intramolecular PPI involving HIV gp41 C-peptide helix, and HIV gp41 N-peptide trimer, which contain C-peptide helix-binding clefts. Here, we used yeast display to screen a library of grafted C-peptide helices for N-peptide trimer recognition. Using 'hits' from yeast display library screening, we evaluated the effect helix mutations have on structure, expression, stability, function (target recognition), and suppression of HIV entry. Copyright © 2017. Published by Elsevier Ltd.

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

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    Ye, Ling; Wen, Zhiyuan; Dong, Ke; Wang, Xi; Bu, Zhigao; Zhang, Huizhong; Compans, Richard W; Yang, Chinglai

    2011-01-01

    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.

  6. Viroporin potential of the lentivirus lytic peptide (LLP domains of the HIV-1 gp41 protein

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    Garry Robert F

    2007-11-01

    Full Text Available Abstract Background Mechanisms by which HIV-1 mediates reductions in CD4+ cell levels in infected persons are being intensely investigated, and have broad implications for AIDS drug and vaccine development. Virally induced changes in membrane ionic permeability induced by lytic viruses of many families contribute to cytopathogenesis. HIV-1 induces disturbances in plasma membrane ion transport. The carboxyl terminus of TM (gp41 contains potential amphipathic α-helical motifs identified through their structural similarities to naturally occurring cytolytic peptides. These sequences have been dubbed lentiviral lytic peptides (LLP -1, -2, and -3. Results Peptides corresponding to the LLP domains (from a clade B virus partition into lipid membranes, fold into α-helices and disrupt model membrane permeability. A peptide corresponding to the LLP-1 domain of a clade D HIV-1 virus, LLP-1D displayed similar activity to the LLP-1 domain of the clade B virus in all assays, despite a lack of amino acid sequence identity. Conclusion These results suggest that the C-terminal domains of HIV-1 Env proteins may form an ion channel, or viroporin. Increased understanding of the function of LLP domains and their role in the viral replication cycle could allow for the development of novel HIV drugs.

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

    National Research Council Canada - National Science Library

    Ye, Ling; Wen, Zhiyuan; Dong, Ke; Wang, Xi; Bu, Zhigao; Zhang, Huizhong; Compans, Richard W; Yang, Chinglai

    2011-01-01

    .... 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...

  8. Amplification of the Gp41 gene for detection of mutations conferring resistance to HIV-1 fusion inhibitors on genotypic assay

    Science.gov (United States)

    Tanumihardja, J.; Bela, B.

    2017-08-01

    Fusion inhibitors have potential for future use in HIV control programs in Indonesia, so the capacity to test resistance to such drugs needs to be developed. Resistance-detection with a genotypic assay began with amplification of the target gene, gp41. Based on the sequence of the two most common HIV subtypes in Indonesia, AE and B, a primer pair was designed. Plasma samples containing both subtypes were extracted to obtain HIV RNA. Using PCR, the primer pair was used to produce the amplification product, the identity of which was checked based on length under electrophoresis. Eleven plasma samples were included in this study. One-step PCR using the primer pair was able to amplify gp41 from 54.5% of the samples, and an unspecific amplification product was seen in 1.1% of the samples. Amplification failed in 36.4% of the samples, which may be due to an inappropriate primer sequence. It was also found that the optimal annealing temperature for producing the single expected band was 57.2 °C. With one-step PCR, the designed primer pair amplified the HIV-1 gp41 gene from subtypes AE and B. However, further research should be done to determine the conditions that will increase the sensitivity and specificity of the amplification process.

  9. Virus like particle based strategy to elicit HIV-protective antibodies to the alpha-helic regions of gp41.

    Science.gov (United States)

    Pastori, C; Tudor, D; Diomede, L; Drillet, A S; Jegerlehner, A; Röhn, T A; Bomsel, M; Lopalco, L

    Natural antibodies to gp41 inhibit HIV-1 replication through the recognition of two different regions, corresponding to the leucine zipper motif in the HR1 alpha-helix and to another motif within HR2 region, hosting 2F5 and 4E10 epitope. This study aimed at reproducing such protective responses through VLP vaccination. Six regions covering the alpha-helical regions of gp41 were conjugated to the surface of AP205 phage-based VLPs. Once administered in mice via systemic or mucosal route, these immunogens elicited high titers of gp41-specific IgG. Immunogenicity and HIV infectivity reduction were obtained either with HR2 regions or with peptides where aminoacid strings were added to either the C-terminus or N-terminus of core epitope in HR1 region. Antibody-dependent cell cytotoxicity (ADCC) activity was induced by one of the HR2 epitopes only. These results may have relevant implications for the development of new vaccinal approaches against HIV infection. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Evaluation of “Credit Card” Libraries for Inhibition of HIV-1 gp41 Fusogenic Core Formation

    Science.gov (United States)

    Xu, Yang; Lu, Hong; Kennedy, Jack P.; Yan, Xuxia; McAllister, Laura; Yamamoto, Noboru; Moss, Jason A.; Boldt, Grant E.; Jiang, Shibo; Janda, Kim D.

    2008-01-01

    Protein-protein interactions are of critical importance in biological systems and small molecule modulators of such protein recognition and intervention processes are of particular interests. To investigate this area of research, we have synthesized small molecule libraries that can disrupt a number of biologically relevant protein-protein interactions. These library members are designed upon planar motifs, appended with a variety of chemical functions, which we have termed as “credit-card” structures. From two of our “credit-card” libraries, a series of molecules were uncovered which act as inhibitors against the HIV-1 gp41 fusogenic 6-helix bundle core formation, viral antigen p24 formation and cell-cell fusion at low micromolar concentrations. From the high-throughput screening assays we utilized, a selective index (SI) value of 4.2 was uncovered for compound 2261, which bodes well for future structure activity investigations and the design of more potent gp41 inhibitors. PMID:16827565

  11. Envelope deglycosylation enhances antigenicity of HIV-1 gp41 epitopes for both broad neutralizing antibodies and their unmutated ancestor antibodies.

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    Ben-Jiang Ma

    2011-09-01

    Full Text Available The HIV-1 gp41 envelope (Env membrane proximal external region (MPER is an important vaccine target that in rare subjects can elicit neutralizing antibodies. One mechanism proposed for rarity of MPER neutralizing antibody generation is lack of reverted unmutated ancestor (putative naive B cell receptor antibody reactivity with HIV-1 envelope. We have studied the effect of partial deglycosylation under non-denaturing (native conditions on gp140 Env antigenicity for MPER neutralizing antibodies and their reverted unmutated ancestor antibodies. We found that native deglycosylation of clade B JRFL gp140 as well as group M consensus gp140 Env CON-S selectively increased the reactivity of Env with the broad neutralizing human mAbs, 2F5 and 4E10. Whereas fully glycosylated gp140 Env either did not bind (JRFL, or weakly bound (CON-S, 2F5 and 4E10 reverted unmutated ancestors, natively deglycosylated JRFL and CON-S gp140 Envs did bind well to these putative mimics of naive B cell receptors. These data predict that partially deglycoslated Env would bind better than fully glycosylated Env to gp41-specific naïve B cells with improved immunogenicity. In this regard, immunization of rhesus macaques demonstrated enhanced immunogenicity of the 2F5 MPER epitope on deglyosylated JRFL gp140 compared to glycosylated JRFL gp140. Thus, the lack of 2F5 and 4E10 reverted unmutated ancestor binding to gp140 Env may not always be due to lack of unmutated ancestor antibody reactivity with gp41 peptide epitopes, but rather, may be due to glycan interference of binding of unmutated ancestor antibodies of broad neutralizing mAb to Env gp41.

  12. HIV-1 Envelope gp41 Antibodies Can Originate from Terminal Ileum B Cells that Share Cross-Reactivity with Commensal Bacteria

    Science.gov (United States)

    Trama, Ashley M.; Moody, M. Anthony; Alam, S. Munir; Jaeger, Frederick H.; Lockwood, Bradley; Parks, Robert; Lloyd, Krissey E.; Stolarchuk, Christina; Scearce, Richard; Foulger, Andrew; Marshall, Dawn J.; Whitesides, John F.; Jeffries, Thomas L.; Wiehe, Kevin; Morris, Lynn; Lambson, Bronwen; Soderberg, Kelly; Hwang, Kwan-Ki; Tomaras, Georgia D.; Vandergrift, Nathan; Jackson, Katherine J.L.; Roskin, Krishna M.; Boyd, Scott D.; Kepler, Thomas B.; Liao, Hua-Xin; Haynes, Barton F.

    2014-01-01

    SUMMARY Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env. PMID:25121750

  13. Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges.

    Science.gov (United States)

    Bomsel, Morgane; Tudor, Daniela; Drillet, Anne-Sophie; Alfsen, Annette; Ganor, Yonatan; Roger, Marie-Gaëlle; Mouz, Nicolas; Amacker, Mario; Chalifour, Anick; Diomede, Lorenzo; Devillier, Gilles; Cong, Zhe; Wei, Qiang; Gao, Hong; Qin, Chuan; Yang, Gui-Bo; Zurbriggen, Rinaldo; Lopalco, Lucia; Fleury, Sylvain

    2011-02-25

    Human immunodeficiency virus (HIV)-1 is mainly transmitted mucosally during sexual intercourse. We therefore evaluated the protective efficacy of a vaccine active at mucosal sites. Macaca mulatta monkeys were immunized via both the intramuscular and intranasal routes with an HIV-1 vaccine made of gp41-subunit antigens grafted on virosomes, a safe delivery carrier approved in humans with self-adjuvant properties. Six months after 13 vaginal challenges with simian-HIV (SHIV)-SF162P3, four out of five vaccinated animals remained virus-negative, and the fifth was only transiently infected. None of the five animals seroconverted to p27gag-SIV. In contrast, all 6 placebo-vaccinated animals became infected and seroconverted. All protected animals showed gp41-specific vaginal IgAs with HIV-1 transcytosis-blocking properties and vaginal IgGs with neutralizing and/or antibody-dependent cellular-cytotoxicity activities. In contrast, plasma IgGs totally lacked virus-neutralizing activity. The protection observed challenges the paradigm whereby circulating antiviral antibodies are required for protection against HIV-1 infection and may serve in designing a human vaccine against HIV-1-AIDS. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. The crystal structure of HIV CRF07 B′/C gp41 reveals a hyper-mutant site in the middle of HR2 heptad repeat

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    Du, Jiansen; Xue, Hailing; Ma, Jing; Liu, Fang [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhou, Jianhua [Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Shao, Yiming [State Key Laboratory for Infectious Disease Prevention and Control, and National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Qiao, Wentao, E-mail: wentaoqiao@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2013-11-15

    HIV CRF07 B′/C is a strain circulating mainly in northwest region of China. The gp41 region of CRF07 is derived from a clade C virus. In order to compare the difference of CRF07 gp41 with that of typical clade B virus, we solved the crystal structure of the core region of CRF07 gp41. Compared with clade B gp41, CRF07 gp41 evolved more basic and hydrophilic residues on its helix bundle surface. Based on sequence alignment, a hyper-mutant cluster located in the middle of HR2 heptads repeat was identified. The mutational study of these residues revealed that this site is important in HIV mediated cell–cell fusion and plays critical roles in conformational changes during viral invasion. - Highlights: • We solved the crystal structure of HIV CRF07 gp41 core region. • A hyper-mutant cluster in the middle of HR2 heptads repeat was identified. • The hyper-mutant site is important in HIV-cell fusion. • The model will help to understand the HIV fusion process.

  15. Membrane mediated regulation in free peptides of HIV-1 gp41: minimal modulation of the hemifusion phase.

    Science.gov (United States)

    Cerasoli, Eleonora; Ravi, Jascindra; Gregor, Craig; Hussain, Rohanah; Siligardi, Giuliano; Martyna, Glenn; Crain, Jason; Ryadnov, Maxim G

    2012-01-21

    Membrane-mediated structural modulation in two short fragments of the human HIV-1 envelope protein gp41 is demonstrated. Derived from the C-terminal membrane proximal external (MPE) and N-terminal fusion peptide proximal (FPP) regions, these peptides are widely separated in the primary sequence but form tertiary contacts during the intermediate (hemifusion) phase of HIV infection. The structural perturbations observed at the membrane interface offer evidence of rudimentary regulatory mechanisms operating in the free peptides which may be relevant in the biological system. No such regulatory phenomena were observed for the individual peptides in a membrane environment or between the peptides in aqueous solutions. Structure determination is made using a combination of circular and linear dichroism spectroscopy (supported by calorimetric measurements) and molecular dynamics simulations. Specifically, we show that these peptides interact locally without the conformational support of helical heptad repeat regions in native gp41 and that the modulation is not mutual with the FPP peptide operating as a primary regulator of the MPE-FPP interactions in the hemifusion phase.

  16. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure

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    Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu

    2016-03-15

    The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.

  17. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

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    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  18. Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.

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    Lynn Morris

    Full Text Available Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER. We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673-680 and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (V(H1-69 and variable kappa light chain (V(K3-20 gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672-680. These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection.

  19. Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting

    Science.gov (United States)

    Morris, Lynn; Chen, Xi; Alam, Munir; Tomaras, Georgia; Zhang, Ruijun; Marshall, Dawn J.; Chen, Bing; Parks, Robert; Foulger, Andrew; Jaeger, Frederick; Donathan, Michele; Bilska, Mira; Gray, Elin S.; Abdool Karim, Salim S.; Kepler, Thomas B.; Whitesides, John; Montefiori, David; Moody, M. Anthony; Liao, Hua-Xin; Haynes, Barton F.

    2011-01-01

    Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673–680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (VH1-69) and variable kappa light chain (VK3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672–680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection. PMID:21980336

  20. Engineering Recombinant Reoviruses To Display gp41 Membrane-Proximal External-Region Epitopes from HIV-1.

    Science.gov (United States)

    Boehme, Karl W; Ikizler, Mine'; Iskarpatyoti, Jason A; Wetzel, J Denise; Willis, Jordan; Crowe, James E; LaBranche, Celia C; Montefiori, David C; Wilson, Gregory J; Dermody, Terence S

    2016-01-01

    The gp41 membrane-proximal external region (MPER) is a target for broadly neutralizing antibody responses against human immunodeficiency virus type 1 (HIV-1). However, replication-defective virus vaccines currently under evaluation in clinical trials do not efficiently elicit MPER-specific antibodies. Structural modeling suggests that the MPER forms an α-helical coiled coil that is required for function and immunogenicity. To maintain the native MPER conformation, we used reverse genetics to engineer replication-competent reovirus vectors that displayed MPER sequences in the α-helical coiled-coil tail domain of viral attachment protein σ1. Sequences in reovirus strain type 1 Lang (T1L) σ1 were exchanged with sequences encoding HIV-1 strain Ba-L MPER epitope 2F5 or the entire MPER. Individual 2F5 or MPER substitutions were introduced at virion-proximal or virion-distal sites in the σ1 tail. Recombinant reoviruses containing heterologous HIV-1 sequences were viable and produced progeny yields comparable to those with wild-type virus. HIV-1 sequences were retained following 10 serial passages in cell culture, indicating that the substitutions were genetically stable. Recombinant viruses engineered to display the 2F5 epitope or full-length MPER in σ1 were recognized by purified 2F5 antibody. Inoculation of mice with 2F5-containing vectors or rabbits with 2F5- or MPER-containing vectors elicited anti-reovirus antibodies, but HIV-1-specific antibodies were not detected. Together, these findings indicate that heterologous sequences that form α-helices can functionally replace native sequences in the α-helical tail domain of reovirus attachment protein σ1. However, although these vectors retain native antigenicity, they were not immunogenic, illustrating the difficulty of experimentally inducing immune responses to this essential region of HIV-1. IMPORTANCE Vaccines to protect against HIV-1, the causative agent of AIDS, are not approved for use. Antibodies that

  1. HIV-1 gp41 and TCRalpha trans-membrane domains share a motif exploited by the HIV virus to modulate T-cell proliferation.

    Directory of Open Access Journals (Sweden)

    Tomer Cohen

    Full Text Available Viruses have evolved several strategies to modify cellular processes and evade the immune response in order to successfully infect, replicate, and persist in the host. By utilizing in-silico testing of a transmembrane sequence library derived from virus protein sequences, we have pin-pointed a nine amino-acid motif shared by a group of different viruses; this motif resembles the transmembrane domain of the alpha-subunit of the T-cell receptor (TCRalpha. The most striking similarity was found within the immunodeficiency virus (SIV and HIV glycoprotein 41 TMD (gp41 TMD. Previous studies have shown that stable interactions between TCRalpha and CD3 are localized to this nine amino acid motif within TCRalpha, and a peptide derived from it (TCRalpha TMD, GLRILLLKV interfered and intervened in the TCR function when added exogenously. We now report that the gp41 TMD peptide co-localizes with CD3 within the TCR complex and inhibits T cell proliferation in vitro. However, the inhibitory mechanism of gp41 TMD differs from that of the TCRalpha TMD and also from the other two known immunosuppressive regions within gp41.

  2. HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions.

    Science.gov (United States)

    Qi, Qianqian; Wang, Qian; Chen, Weizao; Du, Lanying; Dimitrov, Dimiter S; Lu, Lu; Jiang, Shibo

    2017-06-21

    Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT). HIV-1 virions were separated from the inhibitors using PEG-6000, followed by testing of the residual infectivity of the HIV-1 virions. 2Dm2m and 4Dm2m exhibited significant inactivation activity against all HIV-1 strains tested with EC50 values at the low nanomolar level, whereas none of the gp41-targeting peptides showed inactivation activity at concentrations up to 250 nM. Notably, these three peptides significantly enhanced protein-mediated inactivation against cell-free HIV-1 virions, including HIV-1 laboratory-adapted and primary HIV-1 strains, as well as those resistant to T20 or T2635 and virions released from reactivated latently HIV-1-infected cells. These results indicate that the gp120-targeting bispecific multivalent proteins 2Dm2m and 4Dm2m have potential for further development as HIV-1 inactivator-based antiviral drugs for use in the clinic, either alone or in combination with a gp41-targeting HIV-1 fusion inhibitor such as T20, to treat patients with HIV-1 infection and AIDS.

  3. Study of the inhibition capacity of an 18-mer peptide domain of GBV-C virus on gp41-FP HIV-1 activity.

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    Haro, I; Gómara, M J; Galatola, R; Domènech, O; Prat, J; Girona, V; Busquets, M A

    2011-06-01

    The peptide sequence (175-192) RFPFHRCGAGPKLTKDLE (P59) of the E2 envelope protein of GB virus C (GBV-C) has been proved to decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner. Based on these previous results, the main objective of this study was to deepen in the physicochemical aspects involved in this interaction. First, we analyzed the surface activity of P59 at the air-water interface as well as its interaction with zwitterionic or negatively charged lipid monolayers. Then we performed the same experiments with mixtures of P59/gp41-FP. Studies on lipid monolayers helped us to understand the lipid-peptide interaction and the influence of phospholipids on peptide penetration into lipid media. On another hand, studies with lipid bilayers showed that P59 decreased gp41-FP binding to anionic Large Unilamellar Vesicles. Results can be attributed to the differences in morphology of the peptides, as observed by Atomic Force Microscopy. When P59 and gp41-FP were incubated together, annular structures of about 200 nm in diameter appeared on the mica surface, thus indicating a peptide-peptide interaction. All these results confirm the gp41-FP-P59 interaction and thus support the hypothesis that gp41-FP is inhibited by P59. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

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    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

    2015-10-15

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml-1. The median IC50 of neutralized viruses was 0.033 μg ml-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

  5. Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.

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    Mei-Yun Zhang

    Full Text Available Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb, designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env. M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.

  6. Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

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    Xiujuan Zhang

    2018-02-01

    Full Text Available The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.

  7. Kinetics of interaction of HIV fusion protein (gp41) with lipid membranes studied by real-time AFM imaging

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    Bitler, Arkady, E-mail: arkady.bitler@weizmann.ac.il [Department of Chemical Research Support (Israel); Lev, Naama; Fridmann-Sirkis, Yael; Blank, Lior [Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100 (Israel); Cohen, Sidney R. [Department of Chemical Research Support (Israel); Shai, Yechiel [Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100 (Israel)

    2010-05-15

    One of the most important steps in the process of viral infection is a fusion between cell membrane and virus, which is mediated by the viral envelope glycoprotein. The study of activity of the glycoprotein in the post-fusion state is important for understanding the progression of infection. Here we present a first real-time kinetic study of the activity of gp41 (the viral envelope glycoprotein of human immunodeficiency virus-HIV) and its two mutants in the post-fusion state with nanometer resolution by atomic force microscopy (AFM). Tracking the changes in the phosphatidylcholine (PC) and phosphatidylcholine-phosphatidylserine (PC:PS) membrane integrity over one hour by a set of AFM images revealed differences in the interaction of the three types of protein with zwitterionic and negatively charged membranes. A quantitative analysis of the slow kinetics of hole formation in the negatively charged lipid bilayer is presented. Specifically, analysis of the rate of roughness change for the three types of proteins suggests that they exhibit different types of kinetic behavior.

  8. Photoinduced Reactivity of the HIV-1 Envelope Glycoprotein with a Membrane-Embedded Probe Reveals Insertion of Portions of the HIV-1 Gp41 Cytoplasmic Tail into the Viral Membrane†

    Science.gov (United States)

    Viard, Mathias; Ablan, Sherimay D.; Zhou, Ming; Veenstra, Timothy D.; Freed, Eric O.; Raviv, Yossef; Blumenthal, Robert

    2008-01-01

    The interactions of HIV-1 Env (gp120-gp41) with CD4 and coreceptors trigger a barrage of conformational changes in Env that drive the membrane fusion process. Various regions of gp41 have profound effects on HIV entry and budding. However, the precise interactions between gp41 and the membrane have not been elucidated. To examine portions of membrane proteins that are embedded in membrane lipids, we have studied photoinduced chemical reactions in membranes using the lipid bilayer specific probe iodonaphthyl azide (INA). Here we show that in addition to the transmembrane anchor, amphipatic sequences in the cytoplasmic tail (CT) of HIV-1 gp41 are labeled by INA. INA labeling of the HIV-1 gp41 CT was similar whether wild-type or a mutant HIV-1 was used with uncleaved p55 Gag, which does not allow entry. These results shed light on the disposition of the HIV-1 gp41 CT with respect to the membrane. Moreover, our data have general implications for topology of membrane proteins and their in situ interactions with the lipid bilayer. PMID:18198900

  9. Estimating the probability of polyreactive antibodies 4E10 and 2F5 disabling a gp41 trimer after T cell-HIV adhesion.

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    Bin Hu

    2014-01-01

    Full Text Available A few broadly neutralizing antibodies, isolated from HIV-1 infected individuals, recognize epitopes in the membrane proximal external region (MPER of gp41 that are transiently exposed during viral entry. The best characterized, 4E10 and 2F5, are polyreactive, binding to the viral membrane and their epitopes in the MPER. We present a model to calculate, for any antibody concentration, the probability that during the pre-hairpin intermediate, the transient period when the epitopes are first exposed, a bound antibody will disable a trivalent gp41 before fusion is complete. When 4E10 or 2F5 bind to the MPER, a conformational change is induced that results in a stably bound complex. The model predicts that for these antibodies to be effective at neutralization, the time to disable an epitope must be shorter than the time the antibody remains bound in this conformation, about five minutes or less for 4E10 and 2F5. We investigate the role of avidity in neutralization and show that 2F5 IgG, but not 4E10, is much more effective at neutralization than its Fab fragment. We attribute this to 2F5 interacting more stably than 4E10 with the viral membrane. We use the model to elucidate the parameters that determine the ability of these antibodies to disable epitopes and propose an extension of the model to analyze neutralization data. The extended model predicts the dependencies of IC50 for neutralization on the rate constants that characterize antibody binding, the rate of fusion of gp41, and the number of gp41 bridging the virus and target cell at the start of the pre-hairpin intermediate. Analysis of neutralization experiments indicate that only a small number of gp41 bridges must be disabled to prevent fusion. However, the model cannot determine the exact number from neutralization experiments alone.

  10. Monoclonal Antibodies Specific for the V2, V3, CD4-Binding Site, and gp41 of HIV-1 Mediate Phagocytosis in a Dose-Dependent Manner.

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    Musich, Thomas; Li, Liuzhe; Liu, Lily; Zolla-Pazner, Susan; Robert-Guroff, Marjorie; Gorny, Miroslaw K

    2017-04-15

    In light of the weak or absent neutralizing activity mediated by anti-V2 monoclonal antibodies (MAbs), we tested whether they can mediate Ab-dependent cellular phagocytosis (ADCP), which is an important element of anti-HIV-1 immunity. We tested six anti-V2 MAbs and compared them with 21 MAbs specific for V3, the CD4-binding site (CD4bs), and gp41 derived from chronically HIV-1-infected individuals and produced by hybridoma cells. ADCP activity was measured by flow cytometry using uptake by THP-1 monocytic cells of fluorescent beads coated with gp120, gp41, BG505 SOSIP.664, or BG505 DS-SOSIP.664 complexed with MAbs. The measurement of ADCP activity by the area under the curve showed significantly higher activity of anti-gp41 MAbs than of the members of the three other groups of MAbs tested using beads coated with monomeric gp41 or gp120; anti-V2 MAbs were dominant compared to anti-V3 and anti-CD4bs MAbs against clade C gp120 ZM109 ADCP activity mediated by V2 and V3 MAbs was positive against stabilized DS-SOSIP.664 trimer but negligible against SOSIP.664 targets, suggesting that a closed envelope conformation better exposes the variable loops. Two IgG3 MAbs against the V2 and V3 regions displayed dominant ADCP activity compared to a panel of IgG1 MAbs. This superior ADCP activity was confirmed when two of three recombinant IgG3 anti-V2 MAbs were compared to their IgG1 counterparts. The study demonstrated dominant ADCP activity of anti-gp41 against monomers but not trimers, with some higher activity of anti-V2 MAbs than of anti-V3 and anti-CD4bs MAbs. The ability to mediate ADCP suggests a mechanism by which anti-HIV-1 envelope Abs can contribute to protective efficacy. IMPORTANCE Anti-V2 antibodies (Abs) correlated with reduced risk of HIV-1 infection in recipients of the RV144 vaccine, suggesting that they play a protective role, but a mechanism providing such protection remains to be determined. The rare and weak neutralizing activities of anti-V2 MAbs prompted us

  11. The cholesterol-binding motif of the HIV-1 glycoprotein gp41 regulates lateral sorting and oligomerization.

    Science.gov (United States)

    Schwarzer, Roland; Levental, Ilya; Gramatica, Andrea; Scolari, Silvia; Buschmann, Volker; Veit, Michael; Herrmann, Andreas

    2014-10-01

    Enveloped viruses often use membrane lipid rafts to assemble and bud, augment infection and spread efficiently. However, the molecular bases and functional consequences of the partitioning of viral glycoproteins into microdomains remain intriguing questions in virus biology. Here, we measured Foerster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) to study the role of distinct membrane proximal regions of the human immunodeficiency virus glycoprotein gp41 for lipid raft partitioning in living Chinese hamster ovary cells (CHO-K1). Gp41 was labelled with a fluorescent protein at the exoplasmic face of the membrane, preventing any interference of the fluorophore with the proposed role of the transmembrane and cytoplasmic domains in lateral organization of gp41. Raft localization was deduced from interaction with an established raft marker, a fluorescently tagged glycophosphatidylinositol anchor and the cholesterol recognition amino acid consensus (CRAC) was identified as the crucial lateral sorting determinant in CHO-K1 cells. Interestingly, the raft association of gp41 indicates a substantial cell-to-cell heterogeneity of the plasma membrane microdomains. In complementary fluorescence polarization microscopy, a distinct CRAC requirement was found for the oligomerization of the gp41 variants. Our data provide further insight into the molecular basis and biological implications of the cholesterol dependent lateral sorting of viral glycoproteins for virus assembly at cellular membranes. © 2014 John Wiley & Sons Ltd.

  12. Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1 membrane envelope glycoprotein trimer.

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    Nirmin Alsahafi

    Full Text Available The mature human immunodeficiency virus (HIV-1 envelope glycoprotein (Env trimer is produced by proteolytic cleavage of a precursor and consists of three gp120 exterior and three gp41 transmembrane subunits. The metastable Env complex is induced to undergo conformational changes required for virus entry by the binding of gp120 to the receptors, CD4 and CCR5/CXCR4. An isoleucine-to-proline change (I559P in the gp41 ectodomain has been used to stabilize soluble forms of HIV-1 Env trimers for structural characterization and for use as immunogens. In the native membrane-anchored HIV-1BG505 Env, the I559P change modestly decreased proteolytic maturation, increased the non-covalent association of gp120 with the Env trimer, and resulted in an Env conformation distinctly different from that of the wild-type HIV-1BG505 Env. Compared with the wild-type Env, the I559P Env was recognized inefficiently by polyclonal sera from HIV-1-infected individuals, by several gp41-directed antibodies, by some antibodies against the CD4-binding site of gp120, and by antibodies that preferentially recognize the CD4-bound Env. Some of the gp120-associated antigenic differences between the wild-type HIV-1BG505 Env and the I559P mutant were compensated by the SOS disulfide bond between gp120 and gp41, which has been used to stabilize cleaved soluble Env trimers. Nonetheless, regardless of the presence of the SOS changes, Envs with proline 559 were recognized less efficiently than Envs with isoleucine 559 by the VRC01 neutralizing antibody, which binds the CD4-binding site of gp120, and the PGT151 neutralizing antibody, which binds a hybrid gp120-gp41 epitope. The I559P change completely eliminated the ability of the HIV-1BG505 Env to mediate cell-cell fusion and virus entry, and abolished the capacity of the SOS Env to support virus infection in the presence of a reducing agent. These results suggest that differences exist between the quaternary structures of functional Env

  13. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

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    Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

    2017-01-11

    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

  14. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy.

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    Rafiq Nabi

    Full Text Available Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV replication in elite controllers (EC remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC and viremic noncontrollers (HN on highly active antiretroviral therapy (HAART. Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1, a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of

  15. HIV reverse transcriptase inhibiting antibodies detected by a new technique: relation to p24 and gp41 antibodies, HIV antigenemia and clinical variables.

    Science.gov (United States)

    Neumüller, M; Karlsson, A; Lennerstrand, J; Källander, C F; Holmberg, V; Långström-Persson, U; Thorstensson, R; Sandström, E; Gronowitz, J S

    1991-05-01

    A new assay for HIV reverse transcriptase activity inhibiting antibodies (RTI-ab) was used for the analysis of a large collection of sera sampled before and after confirmation of HIV infection. In this assay HIV-RT was preincubated with diluted serum, after which residual RT activity was determined by a technique using a template coupled to macrobeads and 125I-lodo-deoxyuridine-triphosphate as the tracer-substrate. Of the 936 sera analysed, 818 were found positive for RTI-ab, and 824 were positive in Western blot (Wb). The prevalence of RTI-ab compared to Wb was therefore 99.3%. The corresponding figure for 930 sera analysed for envelope-ab, i.e., gp41-ab, was 823 positive, and of these 930 sera 815 were Wb positive, giving a comparative prevalence of 101%. In contrast, only 678 samples of 993 analyzed for core ab, i.e., p24, were positive, giving a prevalence of 77.0% as 880 of these samples were Wb positive. Thus, RTI-ab was as prevalent as gp41-ab, and although the analyses of RTI-ab amounts in different stages showed decreasing levels in stage IV compared to stages II or III, all of the sera except 1 were found positive in stages III and IV. Further, it was found that both the few RTI-ab negative samples in stage II and the few RTI-ab positive samples among Wb negative sera were sampled in connection with seroconversion. The specificity of the RTI-ab assay was 100% in a test of 200 serum samples from HIV negative blood donors. It was concluded that RTI-ab analyses can be made highly sensitive and specific and useful for studies of HIV infection.

  16. The conserved residue Arg46 in the N-terminal heptad repeat domain of HIV-1 gp41 is critical for viral fusion and entry.

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    Xiaoyi Wang

    Full Text Available During the process of HIV-1 fusion with the target cell, the N-terminal heptad repeat (NHR of gp41 interacts with the C-terminal heptad repeat (CHR to form fusogenic six-helix bundle (6-HB core. We previously identified a crucial residue for 6-HB formation and virus entry--Lys63 (K63 in the C-terminal region of NHR (aa 54-70, which forms a hydrophobic cavity. It can form an important salt bridge with Asp121 (D121 in gp41 CHR. Here, we found another important conserved residue for virus fusion and entry, Arg46 (R46, in the N-terminal region of NHR (aa 35-53, which forms a hydrogen bond with a polar residue, Asn43 (N43, in NHR, as a part of the hydrogen-bond network. R46 can also form a salt bridge with a negatively charged residue, Glu137 (E137, in gp41 CHR. Substitution of R46 with the hydrophobic residue Ala (R46A or the negatively charged residue Glu (R46E resulted in disruption of the hydrogen bond network, breakage of the salt bridge and reduction of 6-HB's stability, leading to impairment of viral fusion and decreased inhibition of N36, an NHR peptide. Similarly, CHR peptide C34 with substitution of E137 for Ala (E137A or Arg (E137R also exhibited reduced inhibitory activity against HIV-1 infection and HIV-1-mediated cell-to-cell fusion. These results suggest that the positively charged residue R46 and its hydrogen bond network, together with the salt bridge between R46 and E137, are important for viral fusion and entry and may therefore serve as a target for designing novel HIV fusion/entry inhibitors.

  17. Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope

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    Stanfield, Robyn L.; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S.; Zwick, Michael B.; Wilson, Ian A. (Scripps)

    2012-06-27

    Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K{sub d} of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

  18. Complexes of neutralizing and non-neutralizing affinity matured Fabs with a mimetic of the internal trimeric coiled-coil of HIV-1 gp41.

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    Elena Gustchina

    Full Text Available A series of mini-antibodies (monovalent and bivalent Fabs targeting the conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41 has been previously constructed and reported. Crystal structures of two closely related monovalent Fabs, one (Fab 8066 broadly neutralizing across a wide panel of HIV-1 subtype B and C viruses, and the other (Fab 8062 non-neutralizing, representing the extremes of this series, were previously solved as complexes with 5-Helix, a gp41 pre-hairpin intermediate mimetic. Binding of these Fabs to covalently stabilized chimeric trimers of N-peptides of HIV-1 gp41 (named (CCIZN363 or 3-H has now been investigated using X-ray crystallography, cryo-electron microscopy, and a variety of biophysical methods. Crystal structures of the complexes between 3-H and Fab 8066 and Fab 8062 were determined at 2.8 and 3.0 Å resolution, respectively. Although the structures of the complexes with the neutralizing Fab 8066 and its non-neutralizing counterpart Fab 8062 were generally similar, small differences between them could be correlated with the biological properties of these antibodies. The conformations of the corresponding CDRs of each antibody in the complexes with 3-H and 5-Helix are very similar. The adaptation to a different target upon complex formation is predominantly achieved by changes in the structure of the trimer of N-HR helices, as well as by adjustment of the orientation of the Fab molecule relative to the N-HR in the complex, via rigid-body movement. The structural data presented here indicate that binding of three Fabs 8062 with high affinity requires more significant changes in the structure of the N-HR trimer compared to binding of Fab 8066. A comparative analysis of the structures of Fabs complexed to different gp41 intermediate mimetics allows further evaluation of biological relevance for generation of neutralizing antibodies, as well as provides novel structural insights into immunogen

  19. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Science.gov (United States)

    Leroux-Roels, Geert; Maes, Cathy; Clement, Frédéric; van Engelenburg, Frank; van den Dobbelsteen, Marieke; Adler, Michael; Amacker, Mario; Lopalco, Lucia; Bomsel, Morgane; Chalifour, Anick; Fleury, Sylvain

    2013-01-01

    Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101). Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1. ClinicalTrials.gov NCT01084343.

  20. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

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    Geert Leroux-Roels

    Full Text Available Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101. Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1.ClinicalTrials.gov NCT01084343.

  1. Biophysical Characterization of a Vaccine Candidate against HIV-1: The Transmembrane and Membrane Proximal Domains of HIV-1 gp41 as a Maltose Binding Protein Fusion

    Science.gov (United States)

    Gong, Zhen; Martin-Garcia, Jose M.; Daskalova, Sasha M.; Craciunescu, Felicia M.; Song, Lusheng; Dörner, Katerina; Hansen, Debra T.; Yang, Jay-How; LaBaer, Joshua; Hogue, Brenda G.; Mor, Tsafrir S.; Fromme, Petra

    2015-01-01

    The membrane proximal region (MPR, residues 649–683) and transmembrane domain (TMD, residues 684–705) of the gp41 subunit of HIV-1’s envelope protein are highly conserved and are important in viral mucosal transmission, virus attachment and membrane fusion with target cells. Several structures of the trimeric membrane proximal external region (residues 662–683) of MPR have been reported at the atomic level; however, the atomic structure of the TMD still remains unknown. To elucidate the structure of both MPR and TMD, we expressed the region spanning both domains, MPR-TM (residues 649–705), in Escherichia coli as a fusion protein with maltose binding protein (MBP). MPR-TM was initially fused to the C-terminus of MBP via a 42 aa-long linker containing a TEV protease recognition site (MBP-linker-MPR-TM). Biophysical characterization indicated that the purified MBP-linker-MPR-TM protein was a monodisperse and stable candidate for crystallization. However, crystals of the MBP-linker-MPR-TM protein could not be obtained in extensive crystallization screens. It is possible that the 42 residue-long linker between MBP and MPR-TM was interfering with crystal formation. To test this hypothesis, the 42 residue-long linker was replaced with three alanine residues. The fusion protein, MBP-AAA-MPR-TM, was similarly purified and characterized. Significantly, both the MBP-linker-MPR-TM and MBP-AAA-MPR-TM proteins strongly interacted with broadly neutralizing monoclonal antibodies 2F5 and 4E10. With epitopes accessible to the broadly neutralizing antibodies, these MBP/MPR-TM recombinant proteins may be in immunologically relevant conformations that mimic a pre-hairpin intermediate of gp41. PMID:26295457

  2. Topology of the C-terminal tail of HIV-1 gp41: differential exposure of the Kennedy epitope on cell and viral membranes.

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    Jonathan D Steckbeck

    2010-12-01

    Full Text Available The C-terminal tail (CTT of the HIV-1 gp41 envelope (Env protein is increasingly recognized as an important determinant of Env structure and functional properties, including fusogenicity and antigenicity. While the CTT has been commonly referred to as the "intracytoplasmic domain" based on the assumption of an exclusive localization inside the membrane lipid bilayer, early antigenicity studies and recent biochemical analyses have produced a credible case for surface exposure of specific CTT sequences, including the classical "Kennedy epitope" (KE of gp41, leading to an alternative model of gp41 topology with multiple membrane-spanning domains. The current study was designed to test these conflicting models of CTT topology by characterizing the exposure of native CTT sequences and substituted VSV-G epitope tags in cell- and virion-associated Env to reference monoclonal antibodies (MAbs. Surface staining and FACS analysis of intact, Env-expressing cells demonstrated that the KE is accessible to binding by MAbs directed to both an inserted VSV-G epitope tag and the native KE sequence. Importantly, the VSV-G tag was only reactive when inserted into the KE; no reactivity was observed in cells expressing Env with the VSV-G tag inserted into the LLP2 domain. In contrast to cell-surface expressed Env, no binding of KE-directed MAbs was observed to Env on the surface of intact virions using either immune precipitation or surface plasmon resonance spectroscopy. These data indicate apparently distinct CTT topologies for virion- and cell-associated Env species and add to the case for a reconsideration of CTT topology that is more complex than currently envisioned.

  3. Binding of HIV-1 gp41-directed neutralizing and non-neutralizing fragment antibody binding domain (Fab and single chain variable fragment (ScFv antibodies to the ectodomain of gp41 in the pre-hairpin and six-helix bundle conformations.

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    John M Louis

    Full Text Available We previously reported a series of antibodies, in fragment antigen binding domain (Fab formats, selected from a human non-immune phage library, directed against the internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41. Broadly neutralizing antibodies from that series bind to both the fully exposed N-HR trimer, representing the pre-hairpin intermediate state of gp41, and to partially-exposed N-HR helices within the context of the gp41 six-helix bundle. While the affinities of the Fabs for pre-hairpin intermediate mimetics vary by only 2 to 20-fold between neutralizing and non-neutralizing antibodies, differences in inhibition of viral entry exceed three orders of magnitude. Here we compare the binding of neutralizing (8066 and non-neutralizing (8062 antibodies, differing in only four positions within the CDR-H2 binding loop, in Fab and single chain variable fragment (ScFv formats, to several pre-hairpin intermediate and six-helix bundle constructs of gp41. Residues 56 and 58 of the mini-antibodies are shown to be crucial for neutralization activity. There is a large differential (≥ 150-fold in binding affinity between neutralizing and non-neutralizing antibodies to the six-helix bundle of gp41 and binding to the six-helix bundle does not involve displacement of the outer C-terminal helices of the bundle. The binding stoichiometry is one six-helix bundle to one Fab or three ScFvs. We postulate that neutralization by the 8066 antibody is achieved by binding to a continuum of states along the fusion pathway from the pre-hairpin intermediate all the way to the formation of the six-helix bundle, but prior to irreversible fusion between viral and cellular membranes.

  4. A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains

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    Lu Lu

    2012-12-01

    Full Text Available Abstract Background Most currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells. Although soluble CD4 (sCD4 can inactivate laboratory-adapted HIV-1 strains, it fails to reduce the viral loads in clinical trials because of its low potency against primary isolates and tendency to enhance HIV-1 infection at low concentration. Thus, it is essential to design a better HIV inactivator with improved potency for developing new anti-HIV therapeutics that can actively attack the virus in the circulation before it attaches to and enter into the target cell. Results We engineered a bivalent HIV-1 inactivator, designated 2DLT, by linking the D1D2 domain of CD4 to T1144, the next generation HIV fusion inhibitor, with a 35-mer linker. The D1D2 domain in this soluble 2DLT protein could bind to the CD4-binding site and induce the formation of the gp41 prehairpin fusion-intermediate (PFI, but showed no sCD4-mediated enhancement of HIV-1 infection. The T1144 domain in 2DLT then bound to the exposed PFI, resulting in rapid inactivation of HIV-1 virions in the absence of the target cell. Beside, 2DLT could also inhibit fusion of the virus with the target cell if the virion escapes the first attack of 2DLT. Conclusion This bivalent molecule can serve as a dual barrier against HIV infection by first inactivating HIV-1 virions away from cells and then blocking HIV-1 entry on the target cell surface, indicating its potential for development as a new class of anti-HIV drug.

  5. Transcytosis-blocking abs elicited by an oligomeric immunogen based on the membrane proximal region of HIV-1 gp41 target non-neutralizing epitopes.

    Science.gov (United States)

    Matoba, Nobuyuki; Griffin, Tagan A; Mittman, Michele; Doran, Jeffrey D; Alfsen, Annette; Montefiori, David C; Hanson, Carl V; Bomsel, Morgane; Mor, Tsafrir S

    2008-05-01

    CTB-MPR(649-684), a translational fusion protein consisting of cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produced CTB MPR(649-684) was purified to homogeneity by two affinity chromatography steps. Similar to gp41 and derivatives thereof, the MPR domain can specifically and reversibly self-associate. The affinities of the broadly-neutralizing monoclonal Abs 4E10 and 2F5 to CTB MPR(649-684) were equivalent to their nanomolar affinities toward an MPR peptide. The fusion protein's affinity to GM1 ganglioside was comparable to that of native CTB. Rabbits immunized with CTB-MPR(649-684) raised only a modest level of anti-MPR(649-684) Abs. However, a prime-boost immunization with CTB-MPR(649-684) and a second MPR(649-684)-based immunogen elicited a more productive anti-MPR(649-684) antibody response. These Abs strongly blocked the epithelial transcytosis of a primary subtype B HIV-1 isolate in a human tight epithelial model, expanding our previously reported results using a clade D virus. The Abs recognized epitopes at the N-terminal portion of the MPR peptide, away from the 2F5 and 4E10 epitopes and were not effective in neutralizing infection of CD4+ cells. These results indicate distinct vulnerabilities of two separate interactions of HIV-1 with human cells - Abs against the C-terminal portion of the MPR can neutralize CD4+-dependent infection, while Abs targeting the MPR's N-terminal portion can effectively block galactosyl ceramide dependent transcytosis. We propose that Abs induced by MPR(649-684)-based immunogens may provide broad protective value independent of infection neutralization.

  6. HIV-1 variants with a single-point mutation in the gp41 pocket region exhibiting different susceptibility to HIV fusion inhibitors with pocket- or membrane-binding domain.

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    Lu, Lu; Tong, Pei; Yu, Xiaowen; Pan, Chungen; Zou, Peng; Chen, Ying-Hua; Jiang, Shibo

    2012-12-01

    Enfuvirtide (T20), the first FDA-approved peptide HIV fusion/entry inhibitor derived from the HIV-1 gp41 C-terminal heptad-repeat (CHR) domain, is believed to share a target with C34, another well-characterized CHR-peptide, by interacting with the gp41 N-terminal heptad-repeat (NHR) to form six-helix bundle core. However, our previous studies showed that T20 mainly interacts with the N-terminal region of the NHR (N-NHR) and lipid membranes, while C34 mainly binds to the NHR C-terminal pocket region. But so far, no one has shown that C34 can induce drug-resistance mutation in the gp41 pocket region. In this study, we constructed pseudoviruses in which the Ala at the position of 67 in the gp41 pocket region was substituted with Asp, Gly or Ser, respectively, and found that these mutations rendered the viruses highly resistant to C34, but sensitive to T20. The NHR-peptide N36 with mutations of A67 exhibited reduced anti-HIV-1 activity and decreased α-helicity. The stability of six-helix bundle formed by C34 and N36 with A67 mutations was significantly lower than that formed by C34 and N36 with wild-type sequence. The combination of C34 and T20 resulted in potent synergistic anti-HIV-1 effect against the viruses with mutations in either N- or C-terminal region in NHR. These results suggest that C34 with a pocket-binding domain and T20 containing the N-NHR- and membrane-binding domains inhibit HIV-1 fusion by interacting with different target sites and the combinatorial use of C34 and T20 is expected to be effective against HIV-1 variants resistant to HIV fusion inhibitors. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG-seronegative individuals block HIV-1 epithelial transcytosis and neutralize CD4(+) cell infection: an IgA gene and functional analysis.

    Science.gov (United States)

    Tudor, D; Derrien, M; Diomede, L; Drillet, A-S; Houimel, M; Moog, C; Reynes, J-M; Lopalco, L; Bomsel, M

    2009-09-01

    AIDS is mainly a sexually transmitted disease, and accordingly, mucosal tissues are the primary sites of natural human immunodeficiency virus type-1 (HIV-1) transmission. Mucosal immunoglobulin A (IgA) antibody specific for HIV-1 envelope gp41 subunit is one correlate of protection in individuals who are highly sexually exposed to HIV-1 but remain persistently IgG seronegative (HEPS). Understanding these peculiar IgAs at the gene and functional level is possible only with monoclonal IgAs. We have constructed a mucosal Fab IgA library from HEPS and have characterized a series of HIV-1 IgAs specific for gp41 that, in vitro, are transcytosis-blocking and infection-neutralizing. Characterization of their IgA genes shows that Fab specific for the gp41 membrane-proximal region harbors a long heavy-chain CDR3 loop (CDRH3) similar to the two broadly neutralizing IgG monoclonal antibodies, 2F5 and 4E10. Furthermore, the selected Fab IgA shows extensive somatic mutations that cluster in the CDR regions, indicating that affinity maturation due to an antigen-driven process had occurred in HEPS individuals, presumably upon multiple exposures to HIV. This analysis of HEPS monoclonal IgA gives a unique opportunity to correlate an antibody function (resistance to a pathogen in vivo) with an antibody gene. Such neutralizing monoclonal IgAs could be used in microbicide formulation.

  8. Three-dimensional structure of Schistosoma japonicum glutathione S-transferase fused with a six-amino acid conserved neutralizing epitope of gp41 from HIV

    Science.gov (United States)

    Lim, K.; Ho, J. X.; Keeling, K.; Gilliland, G. L.; Ji, X.; Ruker, F.; Carter, D. C.

    1994-01-01

    The 3-dimensional crystal structure of glutathione S-transferase (GST) of Schistosoma japonicum (Sj) fused with a conserved neutralizing epitope on gp41 (glycoprotein, 41 kDa) of human immunodeficiency virus type 1 (HIV-1) (Muster T et al., 1993, J Virol 67:6642-6647) was determined at 2.5 A resolution. The structure of the 3-3 isozyme rat GST of the mu gene class (Ji X, Zhang P, Armstrong RN, Gilliland GL, 1992, Biochemistry 31:10169-10184) was used as a molecular replacement model. The structure consists of a 4-stranded beta-sheet and 3 alpha-helices in domain 1 and 5 alpha-helices in domain 2. The space group of the Sj GST crystal is P4(3)2(1)2, with unit cell dimensions of a = b = 94.7 A, and c = 58.1 A. The crystal has 1 GST monomer per asymmetric unit, and 2 monomers that form an active dimer are related by crystallographic 2-fold symmetry. In the binding site, the ordered structure of reduced glutathione is observed. The gp41 peptide (Glu-Leu-Asp-Lys-Trp-Ala) fused to the C-terminus of Sj GST forms a loop stabilized by symmetry-related GSTs. The Sj GST structure is compared with previously determined GST structures of mammalian gene classes mu, alpha, and pi. Conserved amino acid residues among the 4 GSTs that are important for hydrophobic and hydrophilic interactions for dimer association and glutathione binding are discussed.

  9. The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM).

    Science.gov (United States)

    Decroly, E; Vandenbranden, M; Ruysschaert, J M; Cogniaux, J; Jacob, G S; Howard, S C; Marshall, G; Kompelli, A; Basak, A; Jean, F

    1994-04-22

    Intracellular proteolytic processing of human immunodeficiency virus envelope glycoprotein precursor (gp160) is an essential step for virus infectivity. Northern blot analysis provided evidence that furin and PC1, but not PC2, are expressed in the CD4+ human lymphoblastoid H9 cell line, suggesting the possible participation of these convertases in human immunodeficiency virus (HIV) gp160 proteolytic processing. Purified PC1 and furin cleaved specifically in vitro gp160 into gp120 (HIV-I SU) and gp41 (HIV-I TM). NH2-terminal sequence analysis of the produced gp41 (HIV-I TM) demonstrated that the cleavage occurred within the sequence Arg-Glu-Lys-Arg decreases Ala-Val-Gly-Ile, which is identical to the bond cleaved in vivo. Transition state analog peptides were designed and tested in vitro for their ability to inhibit the PC1- or furin-mediated gp160 cleavage. The best inhibitor was decanoyl-Arg-Lys-Arg-Arg-psi [CH2NH]-Phe-Leu-Gly-Phe-NH2.

  10. Common tolerance mechanisms, but distinct cross-reactivities associated with gp41 and lipids, limit production of HIV-1 broad neutralizing antibodies 2F5 and 4E10.

    Science.gov (United States)

    Chen, Yao; Zhang, Jinsong; Hwang, Kwan-Ki; Bouton-Verville, Hilary; Xia, Shi-Mao; Newman, Amanda; Ouyang, Ying-Bin; Haynes, Barton F; Verkoczy, Laurent

    2013-08-01

    Developing an HIV-1 vaccine has been hampered by the inability of immunogens to induce broadly neutralizing Abs (BnAbs) that protect against infection. Previously, we used knockin (KI) mice expressing a prototypical gp41-specific BnAb, 2F5, to demonstrate that immunological tolerance triggered by self-reactivity of the 2F5 H chain impedes BnAb induction. In this study, we generate KI models expressing H chains from two other HIV-1 Abs, 4E10 (another self-/polyreactive, anti-gp41 BnAb) and 48d (an anti-CD4 inducible, nonpolyreactive Ab), and find a similar developmental blockade consistent with central B cell deletion in 4E10, but not in 48d VH KI mice. Furthermore, in KI strains expressing the complete 2F5 and 4E10 Abs as BCRs, we find that residual splenic B cells arrest at distinct developmental stages, yet exhibit uniformly low BCR densities, elevated basal activation, and profoundly muted responses to BCR ligation and, when captured as hybridoma mAb lines, maintain their dual (gp41/lipid) affinities and capacities to neutralize HIV-1, establishing a key role for anergy in suppressing residual 2F5- or 4E10-expressing B cells. Importantly, serum IgGs from naive 2F5 and 4E10 KI strains selectively eliminate gp41 and lipid binding, respectively, suggesting B cells expressing 2F5 or 4E10 as BCRs exhibit specificity for a distinct spectrum of host Ags, including selective interactions by 2F5 BCR(+) B cells (i.e., and not 4E10 BCR(+) B cells) with those mimicked by its gp41 neutralization epitope.

  11. Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region.

    Science.gov (United States)

    Banerjee, Saikat; Shi, Heliang; Banasik, Marisa; Moon, Hojin; Lees, William; Qin, Yali; Harley, Andrew; Shepherd, Adrian; Cho, Michael W

    2017-05-01

    The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone. MPER-specific rabbit monoclonal antibodies were generated, including 9F6. Although it lacked neutralizing activity, the target epitope profile of 9F6 closely resembled those of 4E10 and 10E8 ((671)NWFDITNWLWYIK(683)). B-cell repertoire analyses suggested the importance of co-immunizations for maturation of 9F6, which warrants further evaluation of our IPAS-RAM vaccine strategy using an improved priming immunogen. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form.

    Science.gov (United States)

    Pattani, Aditya; McKay, Paul F; Curran, Rhonda M; McCaffrey, Joanne; Gupta, Prem N; Lowry, Deborah; Kett, Vicky L; Shattock, Robin J; McCarthy, Helen O; Malcolm, R Karl

    2012-04-05

    A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Functional characterization of two scFv-Fc antibodies from an HIV controller selected on soluble HIV-1 Env complexes: a neutralizing V3- and a trimer-specific gp41 antibody.

    Science.gov (United States)

    Trott, Maria; Weiβ, Svenja; Antoni, Sascha; Koch, Joachim; von Briesen, Hagen; Hust, Michael; Dietrich, Ursula

    2014-01-01

    HIV neutralizing antibodies (nAbs) represent an important tool in view of prophylactic and therapeutic applications for HIV-1 infection. Patients chronically infected by HIV-1 represent a valuable source for nAbs. HIV controllers, including long-term non-progressors (LTNP) and elite controllers (EC), represent an interesting subgroup in this regard, as here nAbs can develop over time in a rather healthy immune system and in the absence of any therapeutic selection pressure. In this study, we characterized two particular antibodies that were selected as scFv antibody fragments from a phage immune library generated from an LTNP with HIV neutralizing antibodies in his plasma. The phage library was screened on recombinant soluble gp140 envelope (Env) proteins. Sequencing the selected peptide inserts revealed two major classes of antibody sequences. Binding analysis of the corresponding scFv-Fc derivatives to various trimeric and monomeric Env constructs as well as to peptide arrays showed that one class, represented by monoclonal antibody (mAb) A2, specifically recognizes an epitope localized in the pocket binding domain of the C heptad repeat (CHR) in the ectodomain of gp41, but only in the trimeric context. Thus, this antibody represents an interesting tool for trimer identification. MAb A7, representing the second class, binds to structural elements of the third variable loop V3 and neutralizes tier 1 and tier 2 HIV-1 isolates of different subtypes with matching critical amino acids in the linear epitope sequence. In conclusion, HIV controllers are a valuable source for the selection of functionally interesting antibodies that can be selected on soluble gp140 proteins with properties from the native envelope spike.

  14. HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions

    OpenAIRE

    Qi, Qianqian; Wang, Qian; Chen, Weizao; Du, Lanying; Dimitrov, Dimiter S; Lu, Lu; Jiang, Shibo

    2017-01-01

    Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or ...

  15. Antiviral properties of two trimeric recombinant gp41 proteins

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    Nisole Sébastien

    2006-03-01

    Full Text Available Abstract Background As it is the very first step of the HIV replication cycle, HIV entry represents an attractive target for the development of new antiviral drugs. In this context, fusion inhibitors are the third class of anti-HIV drugs to be used for treatment, in combination with nucleoside analogues and antiproteases. But the precise mechanism of HIV fusion mechanism is still unclear. Gp41 ectodomain-derived synthetic peptides represent ideal tools for clarifying this mechanism, in order to design more potent anti-HIV drugs. Results Two soluble trimeric recombinant gp41 proteins, termed Rgp41B and Rgp41A were designed. Both comprise the N- and C-terminal heptad repeat regions of the ectodomain of HIV-1 gp41, connected by a 7-residue hydrophilic linker, in order to mimic the trimeric fusogenic state of the transmembrane glycoprotein. Both recombinant proteins were found to inhibit HIV-1 entry into target cells in a dose-dependent manner. Rgp41A, the most potent inhibitor, was able to inhibit both X4 and R5 isolates into HeLa cells and primary T lymphocytes. X4 viruses were found to be more susceptible than R5 isolates to inhibition by Rgp41A. In order to elucidate how the trimeric recombinant gp41 protein can interfere with HIV-1 entry into target cells, we further investigated its mode of action. Rgp41A was able to bind gp120 but did not induce gp120-gp41 dissociation. Furthermore, this inhibitor could also interfere with a late step of the fusion process, following the mixing of lipids. Conclusion Taken together, our results suggest that Rgp41A can bind to gp120 and also interfere with a late event of the fusion process. Interestingly, Rgp41A can block membrane fusion without preventing lipid mixing. Although further work will be required to fully understand its mode of action, our results already suggest that Rgp41A can interfere with multiple steps of the HIV entry process.

  16. The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

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    Chavez, Leslie L [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

  17. The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study.

    Science.gov (United States)

    Brekke, Kristin; Sommerfelt, Maja; Ökvist, Mats; Dyrhol-Riise, Anne Margarita; Kvale, Dag

    2017-03-24

    Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related to progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based therapeutic vaccine candidate corresponding to C5/gp41732-744 as well as the effects on pre-existing AB levels to C5/gp41732-744, immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T cell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to several of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce C5 exposure and thereby chronic immune activation. Thirty-six HIV patients on effective antiretroviral therapy were randomised to one of three dose levels of Vacc-C5 administered intramuscularly with Alhydrogel or intradermally with GM-CSF as adjuvant through initial immunisation and two booster periods over 26 weeks. Vacc-C5-specific AB were measured by ELISA and T cell responses by both IFN-γ ELISPOT and proliferative assays analysed by flow cytometry. Immune regulation was assessed by functional blockade of the two inhibitory cytokines IL-10 and TGF-β in parallel cultures. Non-parametric statistical tests were applied. Vacc-C5 was found safe and well tolerated in all patients. Only marginal changes in humoral and cellular responses were induced, without any effect on immune activation. Overall, anti-Vacc-C5 AB levels seemed to decrease compared to pre-existing levels. Whereas Vacc-C5-specific CD8+ T cell proliferative responses increased after the first booster period (p = 0.020; CD4+, p = 0.057), they were reduced after the second. In contrast, Vacc-C5-induced T cell regulation increased after completed vaccination (p ≤ 0.027) and was lower at baseline in the few AB responders identified (p = 0.027). The therapeutic HIV vaccine candidate Vacc-C5 safely induced only marginal immune responses

  18. A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition.

    Directory of Open Access Journals (Sweden)

    David Lutje Hulsik

    2013-03-01

    Full Text Available The membrane proximal external region (MPER of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH, 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10.

  19. Antibody neutralization escape mediated by point mutations in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41.

    Science.gov (United States)

    Kalia, Vandana; Sarkar, Surojit; Gupta, Phalguni; Montelaro, Ronald C

    2005-02-01

    The persistence of human immunodeficiency virus type 1 (HIV-1) infection in the presence of robust host immunity has been associated in part with variation in viral envelope proteins leading to antigenic variation and escape from neutralizing antibodies. Previous studies of natural neutralization escape mutants have predominantly focused on gp120 and gp41 ectodomain sequence variations that alter antibody binding via changes in conformation or glycosylation pattern of the Env, likely due to the immune pressure exerted on the exposed ectodomain component of the glycoprotein. Here, we show for the first time a novel mechanism by which point mutations in the intracytoplasmic tail of the transmembrane component (gp41) of envelope can render the virus resistant to neutralization by monoclonal antibodies and broadly neutralizing polyclonal serum antibodies. Point mutations in a highly conserved structural motif within the intracytoplasmic tail resulted in decreased binding of neutralizing antibodies to the Env ectodomain, evidently due to allosteric changes both in the gp41 ectodomain and in gp120. While receptor binding and infectivity of the mutant virus remained unaltered, the changes in Env antigenicity were associated with an increase in neutralization resistance of the mutant virus. These studies demonstrate the structurally integrated nature of gp120 and gp41 and underscore a previously unrecognized potentially critical role for even minor sequence variation of the intracytoplasmic tail in modulating the antigenicity of the ectodomain of HIV-1 envelope glycoprotein complex.

  20. Efficient Fusion at Neutral pH by Human Immunodeficiency Virus gp41 Trimers containing the Fusion Peptide and Transmembrane Domain.

    Science.gov (United States)

    Liang, Shuang; Ratnayake, Punsisi; Keinath, Craig; Jia, Lihui; Wolfe, Robert; Ranaweera, Ahinsa; Weliky, David P

    2018-01-18

    Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins. A gp120 contains ~500-residues and functions to identify target T-cells and macrophages via binding to specific protein receptors of the target cell membrane. Gp120 moves away from the gp41 ectodomain, and the ectodomain is thought to bind to the target cell membrane and mediate membrane fusion. The secondary and tertiary structures of the ectodomain are different in the initial complex with gp120 and the final state without gp120. There isn't yet imaging of gp41 during fusion, so the temporal relationship between the gp41 and membrane structures isn't known. The present study describes biophysical and functional characterization of large gp41 constructs that include the ectodomain and transmembrane domain (TM). Significant fusion is observed of both neutral and anionic vesicles at neutral pH which reflects the expected conditions of HIV/cell fusion. Fusion is enhanced by the FP, which in HIV/cell fusion likely contacts the host membrane, and the MPER and TM, which respectively interfacially contact and traverse the HIV membrane. Initial contact with vesicles is made by protein trimers which are in a native oligomeric state that reflects the initial complex with gp120, and also is commonly observed for the ectodomain without gp120. Circular dichroism data support helical structure for the N-helix, C-helix, and MPER, and non-helical structure for the FP and loop. Distributions of monomer, trimer, and hexamer states are observed by

  1. Early steps of HIV-1 fusion define the sensitivity to inhibitory peptides that block 6-helix bundle formation.

    Directory of Open Access Journals (Sweden)

    Kosuke Miyauchi

    2009-09-01

    Full Text Available The HIV envelope (Env glycoprotein mediates membrane fusion through sequential interactions with CD4 and coreceptors, followed by the refolding of the transmembrane gp41 subunit into the stable 6-helix bundle (6HB conformation. Synthetic peptides derived from the gp41 C-terminal heptad repeat domain (C-peptides potently inhibit fusion by binding to the gp41 pre-bundle intermediates and blocking their conversion into the 6HB. Our recent work revealed that HIV-1 enters cells by fusing with endosomes, but not with the plasma membrane. These studies also showed that, for the large part, gp41 pre-bundles progress toward 6HBs in endosomal compartments and are thus protected from external fusion inhibitors. Here, we examined the consequences of endocytic entry on the gp41 pre-bundle exposure and on the virus' sensitivity to C-peptides. The rates of CD4 and coreceptor binding, as well as the rate of productive receptor-mediated endocytosis, were measured by adding specific inhibitors of these steps at varied times of virus-cell incubation. Following the CD4 binding, CCR5-tropic viruses recruited a requisite number of coreceptors much faster than CXCR4-tropic viruses. The rate of subsequent uptake of ternary Env-CD4-coreceptor complexes did not correlate with the kinetics of coreceptor engagement. These measurements combined with kinetic analyses enabled the determination of the lifetime of pre-bundle intermediates on the cell surface. Overall, these lifetimes correlated with the inhibitory potency of C-peptides. On the other hand, the basal sensitivity to peptides varied considerably among diverse HIV-1 isolates and ranked similarly with their susceptibility to inactivation by soluble CD4. We conclude that both the longevity of gp41 intermediates and the extent of irreversible conformational changes in Env upon CD4 binding determine the antiviral potency of C-peptides.

  2. Solid-state nuclear magnetic resonance (NMR) spectroscopy of human immunodeficiency virus gp41 protein that includes the fusion peptide: NMR detection of recombinant Fgp41 in inclusion bodies in whole bacterial cells and structural characterization of purified and membrane-associated Fgp41.

    Science.gov (United States)

    Vogel, Erica P; Curtis-Fisk, Jaime; Young, Kaitlin M; Weliky, David P

    2011-11-22

    Human immunodeficiency virus (HIV) infection of a host cell begins with fusion of the HIV and host cell membranes and is mediated by the gp41 protein, a single-pass integral membrane protein of HIV. The 175 N-terminal residues make up the ectodomain that lies outside the virus. This work describes the production and characterization of an ectodomain construct containing the 154 N-terminal gp41 residues, including the fusion peptide (FP) that binds to target cell membranes. The Fgp41 sequence was derived from one of the African clade A strains of HIV-1 that have been less studied than European/North American clade B strains. Fgp41 expression at a level of ~100 mg/L of culture was evidenced by an approach that included amino acid type (13)CO and (15)N labeling of recombinant protein and solid-state NMR (SSNMR) spectroscopy of lyophilized whole cells. The approach did not require any protein solubilization or purification and may be a general approach for detection of recombinant protein. The purified Fgp41 yield was ~5 mg/L of culture. SSNMR spectra of membrane-associated Fgp41 showed high helicity for the residues C-terminal of the FP. This was consistent with a "six-helix bundle" (SHB) structure that is the final gp41 state during membrane fusion. This observation and negligible Fgp41-induced vesicle fusion supported a function for SHB gp41 of membrane stabilization and fusion arrest. SSNMR spectra of residues in the membrane-associated FP provided evidence of a mixture of molecular populations with either helical or β-sheet FP conformation. These and earlier SSNMR data strongly support the existence of these populations in the SHB state of membrane-associated gp41. © 2011 American Chemical Society

  3. Designing a Soluble Near Full-Length HIV-1 GP41 Trimer

    Science.gov (United States)

    2012-11-26

    dilutions starting at 50 µg/ml in the growth medium [DMEM with 100 U/ml penicillin , 100 μg/ml streptomycin, 2 mM L-glutamine (Quality Biologics...This work was partly supported by a grant from The National Institute of Allergy and Infectious Diseases (R01AI02725). 1To whom correspondence may be

  4. Stakeholder Engagement in HIV Cure Research: Lessons Learned from Other HIV Interventions and the Way Forward

    Science.gov (United States)

    Chu, Carissa; Ananworanich, Jintanat; Excler, Jean-Louis; Tucker, Joseph D.

    2015-01-01

    Abstract Clinical and basic science advances have raised considerable hope for achieving an HIV cure by accelerating research. This research is dominated primarily by issues about the nature and design of current and future clinical trials. Stakeholder engagement for HIV cure remains in its early stages. Our analysis examines timing and mechanisms of historical stakeholder engagement in other HIV research areas for HIV-uninfected individuals [vaccine development and pre-exposure prophylaxis (PrEP)], and HIV-infected individuals (treatment as prevention, prevention of mother-to-child transmission, and treatment of acute HIV infection) and articulate a plan for HIV cure stakeholder engagement. The experience from HIV vaccine development shows that early engagement of stakeholders helped manage expectations, mitigating the failure of several vaccine trials, while paving the way for subsequent trials. The relatively late engagement of HIV stakeholders in PrEP research may partly explain some of the implementation challenges. The treatment-related stakeholder engagement was strong and community-led from the onset and helped translation from research to implementation. We outline five steps to initiate and sustain stakeholder engagement in HIV cure research and conclude that stakeholder engagement represents a key investment in which stakeholders mutually agree to share knowledge, benefits, and risk of failure. Effective stakeholder engagement prevents misconceptions. As HIV cure research advances from early trials involving subjects with generally favorable prognosis to studies involving greater risk and uncertainty, success may depend on early and deliberate engagement of stakeholders. PMID:26061668

  5. Using theories of practice to understand HIV-positive persons varied engagement with HIV services

    DEFF Research Database (Denmark)

    Skovdal, Morten; Wringe, Alison; Seeley, Janet

    2017-01-01

    engagement with HIV services and were intrinsically linked to the discursive, cultural, political and economic fabric of the participating countries. Conclusion: Practice theory provides HIV researchers and practitioners with a useful vocabulary and analytical tools to understand and steer people...

  6. Fertilization competence of the egg-coating envelope is regulated by direct interaction of dicalcin and gp41, the Xenopus laevis ZP3.

    Science.gov (United States)

    Miwa, Naofumi; Ogawa, Motoyuki; Hanaue, Mayu; Takamatsu, Ken

    2015-08-05

    Fertilization begins with species-restricted interaction of sperm and the egg-coating envelope, which includes a three-dimensional meshwork of filaments composed of glycoproteins (called ZP proteins). Growing evidence has unveiled the molecular nature of ZP proteins; however, the structural property conferring fertilization competence to the egg-coating envelope remains unknown. Here, we show the molecular mechanism that mediates direct interaction between dicalcin, a novel fertilization-suppressive ZP protein-associated protein, and gp41, a Xenopus laevis ortholog of mammalian ZP3, and subsequently demonstrate the structural basis of the envelope for fertilization competence. The interactive regions between dicalcin and gp41 comprised five and nine amino acid residues within dicalcin and twenty-three within gp41 [corrected]. Synthetic peptides corresponding to these regions dramatically affected fertilization: treatment with dicalcin- or gp41-derived peptides decreased or increased fertilization rates, respectively. Prior application of these peptides caused distinct alterations in the in vivo lectin-staining pattern of the envelope as well. Transmission electron microscopy analysis revealed that the dicalcin-derived peptide induced the formation of a well-organized meshwork, whereas the gp41-derived peptide caused the formation of a significantly disorganized meshwork. These findings indicated that the fertilization competence of the egg-coating envelope is crucially regulated by the direct interaction between dicalcin and gp41.

  7. Evidence against Extracellular Exposure of a Highly Immunogenic Region in the C-Terminal Domain of the Simian Immunodeficiency Virus gp41 Transmembrane Protein

    Science.gov (United States)

    Postler, Thomas S.; Martinez-Navio, José M.; Yuste, Eloísa

    2012-01-01

    The generally accepted model for human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein topology includes a single membrane-spanning domain. An alternate model has been proposed which features multiple membrane-spanning domains. Consistent with the alternate model, a high percentage of HIV-1-infected individuals produce unusually robust antibody responses to a region of envelope, the so-called “Kennedy epitope,” that in the conventional model should be in the cytoplasm. Here we show analogous, robust antibody responses in simian immunodeficiency virus SIVmac239-infected rhesus macaques to a region of SIVmac239 envelope located in the C-terminal domain, which in the conventional model should be inside the cell. Sera from SIV-infected rhesus macaques consistently reacted with overlapping oligopeptides corresponding to a region located within the cytoplasmic domain of gp41 by the generally accepted model, at intensities comparable to those observed for immunodominant areas of the surface component gp120. Rabbit serum raised against this highly immunogenic region (HIR) reacted with SIV envelope in cell surface-staining experiments, as did monoclonal anti-HIR antibodies isolated from an SIVmac239-infected rhesus macaque. However, control experiments demonstrated that this surface staining could be explained in whole or in part by the release of envelope protein from expressing cells into the supernatant and the subsequent attachment to the surfaces of cells in the culture. Serum and monoclonal antibodies directed against the HIR failed to neutralize even the highly neutralization-sensitive strain SIVmac316. Furthermore, a potential N-linked glycosylation site located close to the HIR and postulated to be outside the cell in the alternate model was not glycosylated. An artificially introduced glycosylation site within the HIR was also not utilized for glycosylation. Together, these data support the conventional model of SIV envelope as a type Ia

  8. Glycosylation of gp41 of simian immunodeficiency virus shields epitopes that can be targets for neutralizing antibodies.

    Science.gov (United States)

    Yuste, Eloìsa; Bixby, Jacqueline; Lifson, Jeffrey; Sato, Shuji; Johnson, Welkin; Desrosiers, Ronald

    2008-12-01

    Human immunodeficiency virus type 1 and simian immunodeficiency virus possess three closely spaced, highly conserved sites for N-linked carbohydrate attachment in the extracellular domain of the transmembrane protein gp41. We infected rhesus monkeys with a variant of cloned SIVmac239 lacking the second and third sites or with a variant strain lacking all three of SIVmac239's glycosylation sites in gp41. For each mutation, asparagine (N) in the canonical N-X-S/T recognition sequence for carbohydrate attachment was changed to the structurally similar glutamine such that two nucleotide changes would be required for a reversion of the mutated codon. By 16 weeks, experimentally infected monkeys made antibodies that neutralized the mutant viruses to high titers. Such antibodies were not observed in monkeys infected with the parental virus. Thus, new specificities were revealed as a result of the carbohydrate attachment mutations, and antibodies of these specificities had neutralizing activity. Unlike monkeys infected with the parental virus, monkeys infected with the mutant viruses made antibodies that reacted with peptides corresponding to the sequences in this region. Furthermore, there was strong selective pressure for the emergence of variant sequences in this region during the course of infection. By analyzing the neutralization profiles of sequence variants, we were able to define three mutations (Q625R, K631N, and Q634H) in the region of the glycosylation site mutations that conferred resistance to neutralization by plasma from the monkeys infected with mutant virus. Based on the reactivity of antibodies to peptides in this region and the colocalization of neutralization escape mutations, we conclude that N-linked carbohydrates in the ectodomain of the transmembrane protein shield underlying epitopes that would otherwise be the direct targets of neutralizing antibodies.

  9. Challenges to HIV management among youth engaged in HIV care.

    Science.gov (United States)

    Shacham, Enbal; Estlund, Amy L; Tanner, Amanda E; Presti, Rachel

    2017-02-01

    Regardless of medical advancements, new HIV infections persist. Young adults are most often newly infected, thus research is needed to assess medication adherence barriers specific to young adults with HIV. The data were abstracted from medical charts to include both self-reported behavioral and psychological distress data and HIV parameters in 2013 among patients aged 18-30 years. Descriptive and logistic regression analyses were conducted to identify factors related to viral suppression and sexually transmitted infection (STI) status. A total of 335 individuals presented for care during a 12-month period at a single clinic. The majority were African American and had a mean age of 25.6 years. Nearly all had current prescriptions of antiretroviral therapy (ART). Among those receiving ART, almost three-quarters were virally suppressed, as measured by 200 copies/mL. STI tests are conducted annually and by assessed need; 30% of this sample had at least 1 bacterial STI diagnosis within the last year. Psychological distress symptoms were more common among individuals who were not virally suppressed, compared to those who were virally suppressed. Women and individuals with moderate to severe symptoms of depression had higher odds of having unsuppressed viral loads. The independent factors associated with having any STIs were being African American or other minorities and having two or more sex partners. Our findings related to how young adults are managing their HIV care suggest that increased efforts aimed to prevent additional STIs and manage psychological distress will likely reduce transmission risks.

  10. The current status and challenges in the development of fusion inhibitors as therapeutics for HIV-1 infection.

    Science.gov (United States)

    Tan, Jian Jun; Ma, Xue Ting; Liu, Chang; Zhang, Xiao Yi; Wang, Cun Xin

    2013-01-01

    HIV-1 membrane fusion as a part of the process of viral entry in the target cells is facilitated by gp41 and gp120, which are encoded by Env gene of HIV-1. Based on the structure and the mechanism researches, new treatment options targeting HIV-1 entry process have been proposed. Enfuvirtide, which mimics amino acid sequences of viral envelope glycoprotein gp41, is the first HIV-1 fusion inhibitor approved by FDA. Although it fulfills vital functions by binding to gp41 and abolishing the membrane fusion reaction when used in combination, it could induce drug resistant virus variants. Currently, a number of design and modification schemes have been presented, a large number of prospective fusion peptides have emerged. For these fusion inhibitors, multiple mutations in gp41 have been associated with the loss of susceptibility to agents. This review reported the current developments and innovative designs of HIV-1 membrane fusion inhibitors.

  11. Kinetic studies of HIV-1 and HIV-2 envelope glycoprotein-mediated fusion

    Directory of Open Access Journals (Sweden)

    Doms Robert W

    2006-12-01

    Full Text Available Abstract Background HIV envelope glycoprotein (Env-mediated fusion is driven by the concerted coalescence of the HIV gp41 N-helical and C-helical regions, which results in the formation of 6 helix bundles. Kinetics of HIV Env-mediated fusion is an important determinant of sensitivity to entry inhibitors and antibodies. However, the parameters that govern the HIV Env fusion cascade have yet to be fully elucidated. We address this issue by comparing the kinetics HIV-1IIIB Env with those mediated by HIV-2 from two strains with different affinities for CD4 and CXCR4. Results HIV-1 and HIV-2 Env-mediated cell fusion occurred with half times of about 60 and 30 min, respectively. Binding experiments of soluble HIV gp120 proteins to CD4 and co-receptor did not correlate with the differences in kinetics of fusion mediated by the three different HIV Envs. However, escape from inhibition by reagents that block gp120-CD4 binding, CD4-induced CXCR4 binding and 6-helix bundle formation, respectively, indicated large difference between HIV-1 and HIV-2 envelope glycoproteins in their CD4-induced rates of engagement with CXCR4. Conclusion The HIV-2 Env proteins studied here exhibited a significantly reduced window of time between the engagement of gp120 with CD4 and exposure of the CXCR4 binding site on gp120 as compared with HIV-1IIIB Env. The efficiency with which HIV-2 Env undergoes this CD4-induced conformational change is the major cause of the relatively rapid rate of HIV-2 Env mediated-fusion.

  12. HIV-Selectest enzyme immunoassay and rapid test: ability to detect seroconversion following HIV-1 infection.

    Science.gov (United States)

    Khurana, Surender; Norris, Philip J; Busch, Michael P; Haynes, Barton F; Park, Susan; Sasono, Pretty; Mlisana, Koleka; Salim, Abdool Karim; Hecht, Frederick M; Mulenga, Joseph; Chomba, Elwyn; Hunter, Eric; Allen, Susan; Nemo, George; Rodriguez-Chavez, Isaac R; Margolick, Joseph B; Golding, Hana

    2010-01-01

    HIV-Selectest is a serodiagnostic enzyme immunoassay (EIA), containing p6 and gp41 peptides, designed to differentiate between vaccine-induced antibodies and true infections. A rapid test version of the HIV-Selectest was developed. Both assays detected HIV antibodies in men and women within 2 to 4 weeks of infection, with sensitivity similar to third-generation EIAs.

  13. Resistance of Human Immunodeficiency Virus Type 1 to a Third-Generation Fusion Inhibitor Requires Multiple Mutations in gp41 and Is Accompanied by a Dramatic Loss of gp41 Function

    NARCIS (Netherlands)

    Eggink, Dirk; Bontjer, Ilja; Langedijk, Johannes P. M.; Berkhout, Ben; Sanders, Rogier W.

    2011-01-01

    HIV-1 entry into target cells requires the fusion of viral and cellular membranes. This process is an attractive target for therapeutic intervention, and a first-generation fusion inhibitor, T20 (Enfuvirtide; Fuzeon), was approved for clinical use in 2003. Second-generation (T1249) and

  14. Engagement in the HIV Care Continuum among Key Populations in Tijuana, Mexico

    Science.gov (United States)

    Smith, Laramie R; Patterson, Thomas L.; Magis-Rodriguez, Carlos; Ojeda, Victoria D.; Burgos, Luis Jose; Rojas, Sarah A.; Zúñiga, María Luisa; Strathdee, Steffanie A.

    2015-01-01

    In Tijuana, Mexico, HIV is concentrated in sub-epidemics of key populations: persons who inject drugs (PWID), sex workers (SW), and men who have sex with men (MSM). To date, data on engagement in the HIV care continuum among these key populations, particularly in resource-constrained settings, are sparse. We pooled available epidemiological data from six studies (N=3,368) to examine HIV testing and treatment uptake in these key populations; finding an overall HIV prevalence of 5.7%. Of the 191 identified HIV-positive persons, only 11.5% knew their HIV-positive status and 3.7% were on ART. Observed differences between these HIV-positive key populations suggest PWID (vs. non-PWID) were least likely to have previously tested or initiate HIV care. MSM (vs. non-MSM) were more likely to have previously tested but not more likely to know their HIV-positive status. Of persons aware of their HIV-positive status, SW (vs. non-SW) were more likely to initiate HIV care. Findings suggest engagement of key populations in HIV treatment is far below estimates observed for similarly resource-constrained generalized epidemics in sub-Saharan Africa. These data provide one of the first empirical-snapshots highlighting the extent of HIV treatment disparities in key populations. PMID:26354518

  15. Engagement in the HIV Care Continuum among Key Populations in Tijuana, Mexico.

    Science.gov (United States)

    Smith, Laramie R; Patterson, Thomas L; Magis-Rodriguez, Carlos; Ojeda, Victoria D; Burgos, Jose Luis; Rojas, Sarah A; Zúñiga, María Luisa; Strathdee, Steffanie A

    2016-05-01

    In Tijuana, Mexico, HIV is concentrated in sub-epidemics of key populations: persons who inject drugs (PWID), sex workers (SW), and men who have sex with men (MSM). To date, data on engagement in the HIV care continuum among these key populations, particularly in resource-constrained settings, are sparse. We pooled available epidemiological data from six studies (N = 3368) to examine HIV testing and treatment uptake in these key populations; finding an overall HIV prevalence of 5.7 %. Of the 191 identified HIV-positive persons, only 11.5 % knew their HIV-positive status and 3.7 % were on ART. Observed differences between these HIV-positive key populations suggest PWID (vs. non-PWID) were least likely to have previously tested or initiate HIV care. MSM (vs. non-MSM) were more likely to have previously tested but not more likely to know their HIV-positive status. Of persons aware of their HIV-positive status, SW (vs. non-SW) were more likely to initiate HIV care. Findings suggest engagement of key populations in HIV treatment is far below estimates observed for similarly resource-constrained generalized epidemics in sub-Saharan Africa. These data provide one of the first empirical-snapshots highlighting the extent of HIV treatment disparities in key populations.

  16. It’s a Process: Reactions to HIV Diagnosis and Engagement in HIV Care among High-Risk Heterosexuals

    Directory of Open Access Journals (Sweden)

    Alexandra H. Kutnick

    2017-05-01

    Full Text Available After HIV diagnosis, heterosexuals in high-poverty urban areas evidence delays in linkage to care and antiretroviral therapy initiation compared to other groups. Yet barriers to/facilitators of HIV care among these high-risk heterosexuals are understudied. Under the theory of triadic influence, putative barriers to HIV care engagement include individual/attitudinal-level (e.g., fear, medical distrust, social-level (e.g., stigma, and structural-level influences (e.g., poor access. Participants were African-American/Black and Hispanic adults found newly diagnosed with HIV (N = 25 as part of a community-based HIV testing study with heterosexuals in a high-poverty, high-HIV-incidence urban area. A sequential explanatory mixed-methods design was used. We described linkage to HIV care and clinical outcomes [CD4 counts, viral load (VL levels] over 1 year, and then addressed qualitative research questions about the experience of receiving a new HIV diagnosis, its effects on timely engagement in HIV care, and other barriers and facilitators. Participants were assessed five times, receiving a structured interview battery, laboratory tests, data extraction from the medical record, a post-test counseling session, and in-person/phone contacts to foster linkage to care. Participants were randomly selected for qualitative interviews (N = 15/25 that were recorded and transcribed, then analyzed using systematic content analysis. Participants were 50 years old, on average (SD = 7.2 years, mostly male (80%, primarily African-American/Black (88%, and low socioeconomic status. At the first follow-up, rates of engagement in care were high (78%, but viral suppression was modest (39%. Rates improved by the final follow-up (96% engaged, 62% virally suppressed. Two-thirds (69% were adequately retained in care over 1 year. Qualitative results revealed multi-faceted responses to receiving an HIV diagnosis. Problems accepting and internalizing one

  17. Maturation-induced cloaking of neutralization epitopes on HIV-1 particles.

    Directory of Open Access Journals (Sweden)

    Amanda S Joyner

    2011-09-01

    Full Text Available To become infectious, HIV-1 particles undergo a maturation process involving proteolytic cleavage of the Gag and Gag-Pol polyproteins. Immature particles contain a highly stable spherical Gag lattice and are impaired for fusion with target cells. The fusion impairment is relieved by truncation of the gp41 cytoplasmic tail (CT, indicating that an interaction between the immature viral core and gp41 within the particle represses HIV-1 fusion by an unknown mechanism. We hypothesized that the conformation of Env on the viral surface is regulated allosterically by interactions with the HIV-1 core during particle maturation. To test this, we quantified the binding of a panel of monoclonal antibodies to mature and immature HIV-1 particles by immunofluorescence imaging. Surprisingly, immature particles exhibited markedly enhanced binding of several gp41-specific antibodies, including two that recognize the membrane proximal external region (MPER and neutralize diverse HIV-1 strains. Several of the differences in epitope exposure on mature and immature particles were abolished by truncation of the gp41 CT, thus linking the immature HIV-1 fusion defect with altered Env conformation. Our results suggest that perturbation of fusion-dependent Env conformational changes contributes to the impaired fusion of immature particles. Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER.

  18. Suboptimal HIV Testing Uptake Among Men Who Engage in Commercial Sex Work with Men in Asia.

    Science.gov (United States)

    Jin, Harry; Friedman, Mackey Reuel; Lim, Sin How; Guadamuz, Thomas E; Wei, Chongyi

    2016-12-01

    Men who have sex with men and are sex workers (MSMSW) are disproportionately affected by the growing and emerging HIV epidemic. As sex work and same-sex behavior are heavily stigmatized and often illegal in most Asian countries, HIV research focusing on MSMSW has been limited. The goal of this analysis is to examine HIV testing practices and identify correlates of HIV testing among MSMSW in Asia. The Asia Internet MSM Sex Survey, an online cross-sectional survey of 10,861 men who have sex with men (MSM), was conducted in 2010. Data on sociodemographic characteristics, HIV testing behaviors, and sexual behaviors were collected. Five hundred and seventy-four HIV-negative/unknown respondents reported receiving payment for sex with men at least once in the past 6 months and were included in this analysis. Multivariable logistic regression was conducted to identify independent correlates of HIV testing in the past year. About half (48.6%) of the participants had been tested for HIV at least once within the past year, and 30.5% had never been tested. We also found that MSMSW participants who engaged in risky behaviors were less likely to be tested. While one might expect a high HIV testing rate among MSMSW due to the risks associated with engaging in sex work, we found that HIV testing uptake is suboptimal among MSMSW in Asia. These results suggest that targeted HIV prevention and testing promotion among MSMSW are needed.

  19. Development of an Index of Engagement in HIV Care: An Adapted Internet-Based Delphi Process.

    Science.gov (United States)

    Johnson, Mallory O; Koester, Kimberly A; Wood, Troy; Neilands, Torsten B; Pomeranz, Jamie L; Christopoulos, Katerina A

    2017-12-05

    Improving engagement in medical care among persons living with human immunodeficiency virus (HIV) is critical to optimizing clinical outcomes and reducing onward transmission of HIV. However, a clear conceptualization of what it means to be engaged in HIV care is lacking, and thus efforts to measure and enhance engagement in care are limited. This paper describes the use of a modified online Delphi process of consensus building to solicit input from a range of HIV and non-HIV researchers and providers, and to integrate that input with focus group data conducted with HIV-infected patients. The overarching goal was to generate items for a patient-centered measure of engagement in HIV care for use in future research and clinical practice. We recruited 66 expert panelists from around the United States. Starting with six open-ended questions, we used four rounds of online Delphi data collection in tandem with 12 in-person focus groups with patients and cognitive interviews with 25 patients. We recruited 66 expert panelists from around the United States and 64 (97%) were retained for four rounds of data collection. Starting with six open-ended questions, we used four rounds of online Delphi data collection in tandem with 12 in-person focus groups with patients and cognitive interviews with 25 patients. The process resulted in an expansion to 120 topics that were subsequently reduced to 13 candidate items for the planned assessment measure. The process was an efficient method of soliciting input from geographically separated and busy experts across a range of disciplines and professional roles with the aim of arriving at a coherent definition of engagement in HIV care and a manageable set of survey items to assess it. Next steps are to validate the utility of the new measure in predicting retention in care, adherence to treatment, and clinical outcomes among patients living with HIV.

  20. Engagement with Care, Substance Use, and Adherence to Therapy in HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Patrice K. Nicholas

    2014-01-01

    Full Text Available Engagement with care for those living with HIV is aimed at establishing a strong relationship between patients and their health care provider and is often associated with greater adherence to therapy and treatment (Flickinger, Saha, Moore, and Beach, 2013. Substance use behaviors are linked with lower rates of engagement with care and medication adherence (Horvath, Carrico, Simoni, Boyer, Amico, and Petroli, 2013. This study is a secondary data analysis using a cross-sectional design from a larger randomized controlled trial (n=775 that investigated the efficacy of a self-care symptom management manual for participants living with HIV. Participants were recruited from countries of Africa and the US. This study provides evidence that substance use is linked with lower self-reported engagement with care and adherence to therapy. Data on substance use and engagement are presented. Clinical implications of the study address the importance of utilizing health care system and policy factors to improve engagement with care.

  1. Engagement with Care, Substance Use, and Adherence to Therapy in HIV/AIDS.

    Science.gov (United States)

    Nicholas, Patrice K; Willard, Suzanne; Thompson, Clinton; Dawson-Rose, Carol; Corless, Inge B; Wantland, Dean J; Sefcik, Elizabeth F; Nokes, Kathleen M; Kirksey, Kenn M; Hamilton, Mary Jane; Holzemer, William L; Portillo, Carmen J; Rivero Mendez, Marta; Robinson, Linda M; Rosa, Maria; Human, Sarie P; Cuca, Yvette; Huang, Emily; Maryland, Mary; Arudo, John; Eller, Lucille Sanzero; Stanton, Mark A; Driscoll, Marykate; Voss, Joachim G; Moezzi, Shahnaz

    2014-01-01

    Engagement with care for those living with HIV is aimed at establishing a strong relationship between patients and their health care provider and is often associated with greater adherence to therapy and treatment (Flickinger, Saha, Moore, and Beach, 2013). Substance use behaviors are linked with lower rates of engagement with care and medication adherence (Horvath, Carrico, Simoni, Boyer, Amico, and Petroli, 2013). This study is a secondary data analysis using a cross-sectional design from a larger randomized controlled trial (n = 775) that investigated the efficacy of a self-care symptom management manual for participants living with HIV. Participants were recruited from countries of Africa and the US. This study provides evidence that substance use is linked with lower self-reported engagement with care and adherence to therapy. Data on substance use and engagement are presented. Clinical implications of the study address the importance of utilizing health care system and policy factors to improve engagement with care.

  2. Types and delivery of emotional support to promote linkage and engagement in HIV care

    Directory of Open Access Journals (Sweden)

    Cook CL

    2017-12-01

    Full Text Available Christa L Cook,1 Shantrel Canidate,2 Nicole Ennis,3 Robert L Cook4 1Department of Family, Community, and Health System Science, College of Nursing, 2Social and Behavioral Science, College of Public Health and Health Profession, 3Department of Clinical and Health Psychology, College of Public Health and Health Professions, 4Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA Purpose: Despite recommendations for early entry into human immunodeficiency virus (HIV care, many people diagnosed with HIV delay seeking care. Multiple types of social support (ie, cognitive, emotional, and tangible are often needed for someone to transition into HIV care, but a lack of emotional support at diagnosis may be the reason why some people fail to stay engaged in care. Thus, the purpose of this study was to identify how people living with HIV conceptualized emotional support needs and delivery at diagnosis. Method: We conducted a secondary analysis of qualitative data from 27 people living with HIV, many of whom delayed entry into HIV care. Results: Participants described their experiences seeking care after an HIV diagnosis and identified components of emotional support that aided entry into care – identification, connection, and navigational presence. Many participants stated that these types of support were ideally delivered by peers with HIV. Conclusion: In clinical practice, providers often use an HIV diagnosis as an opportunity to educate patients about HIV prevention and access to services. However, this type of social support may not facilitate engagement in care if emotional support needs are not met. Keywords: linkage to care, engagement in care, social support, qualitative

  3. Engagement in sex work does not increase HIV risk for women who inject drugs in Ukraine.

    Science.gov (United States)

    Vasylyeva, Tetyana I; Friedman, Samuel R; Gensburg, Lenore; Smyrnov, Pavlo

    2017-09-01

    We studied the association between sex in exchange for money, drugs or goods and HIV for women who inject drugs (WWID) in Ukraine, as previous data on this association from the post-USSR region are contradictory. Data come from the Integrated Bio-Behavioral Survey of Ukrainian people who inject drugs collected in 2011 using respondent-driven sampling. Participants were interviewed and tested with rapid HIV tests. The sample included 2465 WWID (24% HIV positive); 214 (8.7%) of which reported having had exchange sex during the last 90 days. Crude analysis showed no association between exchange sex and HIV (OR = 0.644; 95% CI 0.385-1.077). No confounders were found to alter this result in a multivariable analysis. Further modeling showed that exchange sex modifies association between HIV and alcohol use: no association between HIV and daily alcohol use was found for those women who exchanged sex (OR = 1.699, 95% CI 0.737-3.956); while not engaging in sex work and daily using alcohol reduced odds to be HIV infected (OR = 0.586, 95% CI 0.389-0.885). Exchange sex may have less impact on the HIV status of WWID who are exposed to injecting risks. The finding that daily alcohol use appears protective against HIV among WWID who do not exchange sex requires more research.

  4. Give Me a Like: How HIV/AIDS Nonprofit Organizations Can Engage Their Audience on Facebook.

    Science.gov (United States)

    Huang, Yu-Chao; Lin, Yi-Pin; Saxton, Gregory D

    2016-12-01

    With the rapid proliferation and adoption of social media among healthcare professionals and organizations, social media-based HIV/AIDS intervention programs have become increasingly popular. However, the question of the effectiveness of the HIV/AIDS messages disseminated on social media has received scant attention in the literature. The current study applies content analysis to examine the relationship between Facebook messaging strategies employed by 110 HIV/AIDS nonprofit organizations and audience reactions in the form of liking, commenting, and sharing behavior. The results reveal that HIV/AIDS nonprofit organizations often use informational messages as one-way communication with their audience instead of dialogic interactions. Some specific types of messages, such as medication-focused messages, engender better audience engagement; in contrast, event-related messages and call-to-action messages appear to translate into lower corresponding audience reactions. The findings provide guidance to HIV/AIDS organizations in developing effective social media communication strategies.

  5. 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.

  6. How older black women perceive the effects of stigma and social support on engagement in HIV care.

    Science.gov (United States)

    McDoom, M Maya; Bokhour, Barbara; Sullivan, Meg; Drainoni, Mari-Lynn

    2015-02-01

    As black women over age 50 represent a growing share of women living with HIV, understanding what helps them persist and engage in ongoing HIV care will become increasingly important. Delineating the specific roles of social support and stigma on HIV care experiences among this population remains unclear. We qualitatively examined how experiences with stigma and social support either facilitated or inhibited engagement in HIV care, from the perspective of older black women. Semi-structured interviews were conducted with 20 older black women currently receiving HIV care at primary care clinics in the Metropolitan Boston area. Women expressed that experiences with stigma and seeking support played an important role in evaluating the risks and benefits of engaging in care. Social support facilitated their ability to engage in care, while stigma interfered with their ability to engage in care throughout the course of their illness. Providers in particular, can facilitate engagement by understanding the changes in these women's lives as they struggle with stigma and disclosure while engaging in HIV care. The patient's experiences with social support and stigma and their perceptions about engagement are important considerations for medical teams to tailor efforts to engage older black women in regular HIV care.

  7. Confirmation of HIV seropositivity: comparison of a novel radioimmunoprecipitation assay to immunoblotting and virus culture

    NARCIS (Netherlands)

    Tersmette, M.; Lelie, P. N.; van der Poel, C. L.; Wester, M. R.; de Goede, R. E.; Lange, J. M.; Miedema, F.; Huisman, J. G.

    1988-01-01

    A recently developed radioimmunoprecipitation assay, using 125I-labeled human immunodeficiency virus (HIV) viral proteins enriched for glycoproteins gp120env, gp41env (GRIPA), was compared to the immunoblot assay with respect to sensitivity and specificity for the detection of antibodies to HIV.

  8. Disengagement and Engagement Coping with HIV/AIDS Stigma and Psychological Well-Being of People with HIV/AIDS

    Science.gov (United States)

    Varni, Susan E.; Miller, Carol T.; McCuin, Tara; Solomon, Sondra E.

    2012-01-01

    The stigma associated with HIV/AIDS poses a psychological challenge to people living with HIV/AIDS. We hypothesized that that the consequences of stigma-related stressors on psychological well-being would depend on how people cope with the stress of HIV/AIDS stigma. Two hundred participants with HIV/AIDS completed a self-report measure of enacted stigma and felt stigma, a measure of how they coped with HIV/AIDS stigma, and measures of depression and anxiety, and self-esteem. In general, increases in felt stigma (concerns with public attitudes, negative self-image, and disclosure concerns) coupled with how participants reported coping with stigma (by disengaging from or engaging with the stigma stressor) predicted self-reported depression, anxiety, and self-esteem. Increases in felt stigma were associated with increases in anxiety and depression among participants who reported relatively high levels of disengagement coping compared to participants who reported relatively low levels of disengagement coping. Increases in felt stigma were associated with decreased self-esteem, but this association was attenuated among participants who reported relatively high levels of engagement control coping. The data also suggested a trend that increases in enacted stigma predicted increases in anxiety, but not depression, among participants who reported using more disengagement coping. Mental health professionals working with people who are HIV positive should consider how their clients cope with HIV/AIDS stigma and consider tailoring current therapies to address the relationship between stigma, coping, and psychological well-being. PMID:22611302

  9. Exploring How Substance Use Impedes Engagement along the HIV Care Continuum: A Qualitative Study

    Science.gov (United States)

    Gwadz, Marya; de Guzman, Rebecca; Freeman, Robert; Kutnick, Alexandra; Silverman, Elizabeth; Leonard, Noelle R.; Ritchie, Amanda Spring; Muñoz-Plaza, Corinne; Salomon, Nadim; Wolfe, Hannah; Hilliard, Christopher; Cleland, Charles M.; Honig, Sylvie

    2016-01-01

    Drug use is associated with low uptake of HIV antiretroviral therapy (ART), an under-studied step in the HIV care continuum, and insufficient engagement in HIV primary care. However, the specific underlying mechanisms by which drug use impedes these HIV health outcomes are poorly understood. The present qualitative study addresses this gap in the literature, focusing on African-American/Black and Hispanic persons living with HIV (PLWH) who had delayed, declined, or discontinued ART and who also were generally poorly engaged in health care. Participants (N = 37) were purposively sampled from a larger study for maximum variation on HIV indices. They engaged in 1–2 h audio-recorded in-depth semi-structured interviews on HIV histories guided by a multilevel social-cognitive theory. Transcripts were analyzed using a systematic content analysis approach. Consistent with the existing literature, heavy substance use, but not casual or social use, impeded ART uptake, mainly by undermining confidence in medication management abilities and triggering depression. The confluence of African-American/Black or Hispanic race/ethnicity, poverty, and drug use was associated with high levels of perceived stigma and inferior treatment in health-care settings compared to their peers. Furthermore, providers were described as frequently assuming participants were selling their medications to buy drugs, which strained provider–patient relationships. High levels of medical distrust, common in this population, created fears of ART and of negative interactions between street drugs and ART, but participants could not easily discuss this concern with health-care providers. Barriers to ART initiation and HIV care were embedded in other structural- and social-level challenges, which disproportionately affect low-income African-American/Black and Hispanic PLWH (e.g., homelessness, violence). Yet, HIV management was cyclical. In collaboration with trusted providers and ancillary staff

  10. Association between patient engagement in HIV care and antiretroviral therapy medication adherence: cross-sectional evidence from a regional HIV care center in Kenya.

    Science.gov (United States)

    Mûnene, Edwin; Ekman, Björn

    2015-01-01

    Consistent individual effort in engagement in HIV medical services has been associated with positive health outcomes in people living with HIV (PLHIV). However, whether these benefits are facilitated by improved medication adherence has not been widely studied. This study aimed to investigate the marginal effect of engagement in HIV care on medication adherence at a public health facility in Kenya. Between February and April 2013, 392 patients on HIV care at Nyeri Provincial General Hospital participated in this study. Data were collected using a self-administered health survey questionnaire assessing health and sociodemographic statuses. A manual stepwise general linear model was specified to measure the effect of engagement in HIV and other associated predictors on medication adherence. Engagement in HIV care was significantly associated with log-transformed medication adherence in the sample (100·β = 9.2%, 95% CI 3.2-15.1) irrespective of gender and other selected predictors. Longer duration on antiretroviral therapy was also a significant predictor of better medication adherence (100·β = 3.2%, 95% CI 2.3-4.1). Despite inter-gender differences in adherence and engagement determinants, gender's independent effect on medication adherence and engagement in care were not statistically significant. Poor medication adherence was associated with lower patient engagement in HIV care services, suggesting that interventions which remove obstacles to regular observance of scheduled clinic appointments and eventual retention may have a beneficial impact on medication adherence and, accordingly, health outcomes in PLHIV.

  11. Bridging the social and the biomedical: engaging the social and political sciences in HIV research.

    Science.gov (United States)

    Kippax, Susan C; Holt, Martin; Friedman, Samuel R

    2011-09-27

    This supplement to the Journal of the International AIDS Society focuses on the engagement of the social and political sciences within HIV research and, in particular, maintaining a productive relationship between social and biomedical perspectives on HIV. It responds to a number of concerns raised primarily by social scientists, but also recognized as important by biomedical and public health researchers. These concerns include how best to understand the impact of medical technologies (such as HIV treatments, HIV testing, viral load testing, male circumcision, microbicides, and pre-and post-exposure prophylaxis) on sexual cultures, drug practices, relationships and social networks in different cultural, economic and political contexts. The supplement is also concerned with how we might examine the relationship between HIV prevention and treatment, understand the social and political mobilization required to tackle HIV, and sustain the range of disciplinary approaches needed to inform and guide responses to the global pandemic. The six articles included in the supplement demonstrate the value of fostering high quality social and political research to inform, guide and challenge our collaborative responses to HIV/AIDS.

  12. Prevalence of human immunodeficiency virus (HIV) infection among ...

    African Journals Online (AJOL)

    AJB SERVER

    2007-02-05

    Feb 5, 2007 ... and Nef regulatory proteins that are translated from spliced mRNA species. The HIV structure consist of a lipoprotein surface studded by about 72 envelop knobs consisting of the glycoproteins gp120, the surfaces (SU) protein and gp41, the transmembrane (TM) protein. Insi- de this lipid bilayer is a matrix ...

  13. Map of sequential B cell epitopes of the HIV-1 transmembrane protein using human antibodies as probe

    NARCIS (Netherlands)

    Goudsmit, J.; Meloen, R. H.; Brasseur, R.

    1990-01-01

    Antibodies of individuals infected with the human immunodeficiency virus type 1 (HIV-1) were used to probe the antigenicity of the HIV-1 transmembrane protein of 41 kD (gp41) by antibody-reactive peptide scanning (Pepscan). Eleven distinct sequential antibody-binding sites were defined by testing

  14. Patient-provider perceptions on engagement in HIV care in Argentina.

    Science.gov (United States)

    Bofill, Lina Margarita; Lopez, Maria; Dorigo, Analia; Bordato, Alejandra; Lucas, Mar; Cabanillas, Graciela Fernandez; Sued, Omar; Cahn, Pedro; Cassetti, Isabel; Weiss, Stephen; Jones, Deborah

    2014-01-01

    Approximately 30% of patients participating in the national antiretroviral therapy (ART) program in Argentina fail to achieve an undetectable viral load, and approximately 25% are not retained in care. This qualitative study was designed to explore and identify factors associated with engagement and retention in public and private health care in Buenos Aires, Argentina. Qualitative data from key informants (n = 12) and focus groups (n = 4 groups) of patients and providers from private and public HIV treatment facilities were recorded and transcribed. Predetermined and arising themes related to adherence, engagement, and retention in care were coded and analyzed using qualitative data analysis software. Reasons identified for patients' lack of adherence or engagement in care differed between patients and providers, and patients attributed limitations to low self-efficacy, fear and concerns about HIV, and lack of provider involvement in treatment. In contrast, providers viewed themselves as decision-makers in patient care and patients as responsible for their own nonadherence due to lack of commitment to their own health or due to medication side effects. Patients reported health care system limitations and HIV concerns contributed to a lack of engagement, and providers identified limited HIV literacy and stigma as additional problems. Both agreed that chronic illness and substance addiction impacted adherence and retention, and agreed on the importance of trust, honesty, and communication in the patient-provider relationship. Results support the incorporation of system-, provider-, and patient-focused components into interventions to facilitate patient engagement, adherence, and retention in public and private settings in Argentina.

  15. Patient–provider perceptions on engagement in HIV care in Argentina

    Science.gov (United States)

    Bofill, Lina Margarita; Lopez, Maria; Dorigo, Analia; Bordato, Alejandra; Lucas, Mar; Cabanillas, Graciela Fernandez; Sued, Omar; Cahn, Pedro; Cassetti, Isabel; Weiss, Stephen; Jones, Deborah

    2014-01-01

    Approximately 30% of patients participating in the national antiretroviral therapy (ART) program in Argentina fail to achieve an undetectable viral load, and approximately 25% are not retained in care. This qualitative study was designed to explore and identify factors associated with engagement and retention in public and private health care in Buenos Aires, Argentina. Qualitative data from key informants (n = 12) and focus groups (n = 4 groups) of patients and providers from private and public HIV treatment facilities were recorded and transcribed. Predetermined and arising themes related to adherence, engagement, and retention in care were coded and analyzed using qualitative data analysis software. Reasons identified for patients’ lack of adherence or engagement in care differed between patients and providers, and patients attributed limitations to low self-efficacy, fear and concerns about HIV, and lack of provider involvement in treatment. In contrast, providers viewed themselves as decision-makers in patient care and patients as responsible for their own nonadherence due to lack of commitment to their own health or due to medication side effects. Patients reported health care system limitations and HIV concerns contributed to a lack of engagement, and providers identified limited HIV literacy and stigma as additional problems. Both agreed that chronic illness and substance addiction impacted adherence and retention, and agreed on the importance of trust, honesty, and communication in the patient–provider relationship. Results support the incorporation of system-, provider-, and patient-focused components into interventions to facilitate patient engagement, adherence, and retention in public and private settings in Argentina. PMID:24138788

  16. Global burden of HIV among men who engage in transactional sex: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Catherine E Oldenburg

    Full Text Available Men who engage in transactional sex, the exchange of sex for money, goods, or other items of value, are thought to be at increased risk of HIV, but there have been no systematic attempts to characterize HIV burden in this population. We undertook a systematic review and meta-analysis to quantify the burden in this population compared with that of men in the general population to better inform future HIV prevention efforts.We searched seven electronic databases, national surveillance reports, and conference abstracts for studies of men who engage in transactional sex published between 2004-2013. Random effects meta-analysis was used to determine pooled HIV prevalence and prevalence ratios (PR for the difference in HIV prevalence among men who engage in transactional sex as compared to general population men.Of 66 studies included representing 31,924 men who had engaged in transactional sex in 28 countries, pooled biological assay-confirmed HIV prevalence was 10.5% (95% CI = 9.4 to 11.5%. The highest pooled HIV prevalence was in Sub-Saharan Africa (31.5%, 95% CI = 21.6 to 41.5%, followed by Latin America (19.3%, 95% CI = 15.5 to 23.1%, North America (16.6%, 95% CI = 3.7 to 29.5%, and Europe (12.2%, 95% CI = 6.0 to 17.2%. Men who engaged in transactional sex had an elevated burden of HIV compared to the general male population (PR = 20.7, 95% CI = 16.8 to 25.5.The global burden of HIV is disproportionately high among men who engage in transactional sex compared with the general male population. There is an urgent need to include this population in systematic surveillance as well as to scale-up access to quality HIV prevention programs.

  17. Sources and types of social support that influence engagement in HIV care among Latinos and African Americans.

    Science.gov (United States)

    George, Sheba; Garth, Belinda; Wohl, Amy Rock; Galvan, Frank H; Garland, Wendy; Myers, Hector F

    2009-11-01

    The change in HIV from acute to chronic disease due to the introduction of HAART in the mid-1990s increased the importance of its successful management and imposed substantial lifestyle adjustments on HIV-positive people and their support networks. Few studies have examined the sources and types of social support and the areas of care relevant for engagement in HIV treatment among HIV-positive Latinos and African Americans. This paper reports the results of 24 semi-structured in-depth interviews that were conducted with HIV-positive African American and Latino women and men who have sex with men. Formal networks were found to be more critical for engagement in HIV-specific medical care; specifically, study participants relied primarily on health care providers for support in accessing and maintaining illness-specific care. In contrast, informal networks (family and friends) were crucial for other general subsistence care, such as emotional, household-related, and financial support.

  18. Toward an endgame: finding and engaging people unaware of their HIV-1 infection in treatment and prevention.

    Science.gov (United States)

    Burns, David N; DeGruttola, Victor; Pilcher, Christopher D; Kretzschmar, Mirjam; Gordon, Christopher M; Flanagan, Elizabeth H; Duncombe, Christopher; Cohen, Myron S

    2014-03-01

    Epidemic modeling suggests that a major scale-up in HIV treatment could have a dramatic impact on HIV incidence. This has led both researchers and policymakers to set a goal of an "AIDS-Free Generation." One of the greatest obstacles to achieving this objective is the number of people with undiagnosed HIV infection. Despite recent innovations, new research strategies are needed to identify, engage, and successfully treat people who are unaware of their infection.

  19. Immunogenicity of HIV-1LAI gp160 and env peptides in squirrel monkey Saimiri sciureus using alumine and experimental adjuvants.

    Science.gov (United States)

    Perraut, R; Chouteau, P; Moog, C; Bonnemains, B; Kieny, M P

    1996-12-01

    Since the identification of the HIV virus, important advances have been achieved in the definition of potential subunit vaccines. We investigated the immunogenicity of a recombinant gp160 antigen and of two gp41 peptides from HIV-1LAI associated with seven different adjuvant formulations in squirrel monkeys. All animals were immunized twice with gp160 and then with a gp41 peptide using the same formulation. All adjuvants used led to a subsequent antibody response against gp160, and 55% of the animals immunized developed anti-gp160 antibodies that could neutralize the virus in vitro. Specific anti-gp41 antibody response was also observed. Results obtained underlined the key role of the adjuvant formulation in the antibody response against a given part of the immunogen, and indicate that such immunogenicity-related investigation can be carried out conveniently in the squirrel monkey Saimiri sciureus.

  20. What role can gender-transformative programming for men play in increasing men's HIV testing and engagement in HIV care and treatment in South Africa?

    Science.gov (United States)

    Fleming, Paul J; Colvin, Chris; Peacock, Dean; Dworkin, Shari L

    2016-11-01

    Men are less likely than women to test for HIV and engage in HIV care and treatment. We conducted in-depth interviews with men participating in One Man Can (OMC) - a rights-based gender equality and health programme intervention conducted in rural Limpopo and Eastern Cape, South Africa - to explore masculinity-related barriers to HIV testing/care/treatment and how participation in OMC impacted on these. Men who participated in OMC reported an increased capability to overcome masculinity-related barriers to testing/care/treatment. They also reported increased ability to express vulnerability and discuss HIV openly with others, which led to greater willingness to be tested for HIV and receive HIV care and treatment for those who were living with HIV. Interventions that challenge masculine norms and promote gender equality (i.e. gender-transformative interventions) represent a promising new approach to address men's barriers to testing, care and treatment.

  1. [Development of a rapid test kit for antibody to HIV by nano immunomagnetic lateral flow method].

    Science.gov (United States)

    Yang, Fa-qing; Lee, Tony; Wang, Chao-nan; Sun, Shu-ye; Li, Shan-shan; Tian, Hui

    2010-06-01

    To develop a rapid test kit for antibody to HIV by nano immunomagnetic lateral flow method. A rapid test kit was developed by conjugation of the HIV antigen gp41 and gp36 to 200nm super paramagnetic particles by carbodiimide (EDC) and coating of the HIV antigen gp41 and gp36 to nitrocellulose membrane. Then the kit was evaluated with serials of experiments. The kit was qualified with examination of national reference panel of anti-HIV antibody for colloidal gold diagnostic kit. The sensitivity was 100% by tested with 20 HIV antibody positive sera, the specificity was 98.5% by tested with 600 HIV antibody negative sera, respectively. The stability of the kit was over 12 month by storage at room temperature. A diagnostic kit for antibody to HIV was developed with the advantages of convenience, rapid test, good stability and point of care.

  2. Sex Practices by HIV Awareness and Engagement in the Continuum of Care Among MSM: A National HIV Behavioral Surveillance Analysis in 21 U.S. Cities.

    Science.gov (United States)

    Whitham, Hilary K; Sansom, Stephanie L; Wejnert, Cyprian; Finlayson, Teresa; Huang, Ya-Lin A; An, Qian; Paz-Bailey, Gabriela

    2018-03-01

    Using National HIV Behavioral Surveillance (NHBS) cross-sectional survey and HIV testing data in 21 U.S. metropolitan areas, we identify sex practices among sexually active men who have sex with men (MSM) associated with: (1) awareness of HIV status, and (2) engagement in the HIV care continuum. Data from 2008, 2011, and 2014 were aggregated, yielding a sample of 5079 sexually active MSM living with HIV (MLWH). Participants were classified into HIV status categories: (1) unaware; (2) aware and out of care; (3) aware and in care without antiretroviral therapy (ART); and (4) aware and on ART. Analyses were conducted examining sex practices (e.g. condomless sex, discordant condomless sex, and number of sex partners) by HIV status. Approximately 30, 5, 10 and 55% of the sample was classified as unaware, aware and out of care, aware and in care without ART, and aware and on ART, respectively. Unaware MLWH were more likely to report condomless anal sex with a last male partner of discordant or unknown HIV status (25.9%) than aware MLWH (18.0%, p value aware MLWH (17.3 and 5.6%, p-value HIV status (ranging from 17.7 to 21.3%), and median number of both male and female sex partners were similar. In conclusion, awareness of HIV and engagement in care was not consistently associated with protective sex practices, highlighting the need for continued prevention efforts.

  3. Development and pilot testing of an intervention to promote care engagement and adherence among HIV-positive Kenyan MSM

    NARCIS (Netherlands)

    Graham, Susan M.; Micheni, Murugi; Kombo, Bernadette; van der Elst, Elisabeth M.; Mugo, Peter M.; Kivaya, Esther; Aunon, Frances; Kutner, Bryan; Sanders, Eduard J.; Simoni, Jane M.

    2015-01-01

    In many African settings, MSM are a stigmatized group whose access to and engagement in HIV care may be challenging. Our aim was to design a targeted, culturally appropriate intervention to promote care engagement and antiretroviral therapy (ART) adherence for MSM in coastal Kenya, and describe

  4. Daily Marijuana Use is Associated with Missed Clinic Appointments Among HIV-Infected Persons Engaged in HIV Care.

    Science.gov (United States)

    Kipp, Aaron M; Rebeiro, Peter F; Shepherd, Bryan E; Brinkley-Rubinstein, Lauren; Turner, Megan; Bebawy, Sally; Sterling, Timothy R; Hulgan, Todd

    2017-07-01

    We assessed the association between marijuana use and retention in HIV care through a retrospective cohort study of patients engaged in care at a large HIV clinic in 2011 and 2012. Two different retention outcomes were assessed: not meeting the Institute of Medicine's (IOM) retention definition (≥2 provider visits ≥90 days apart in a calendar year) and no-show visits. Any marijuana use and frequency of marijuana use were obtained from a substance use screening questionnaire administered at each clinic visit. Modified Poisson regression was used to estimate risk ratios and 95% confidence intervals for the association between marijuana use and retention outcomes. Marijuana use was reported by 17% of 1791 patients and 21% were not retained (IOM definition). Marijuana use was not associated with the IOM retention outcome, but was associated with missing the next scheduled appointment. A non-linear dose-response was observed for frequency of marijuana use and missed visits, with daily users having the highest risk compared to non-users. Daily marijuana use had a negative impact on HIV clinic attendance. Further research is needed to elucidate the mechanisms by which marijuana use affects this outcome to inform targeted interventions.

  5. HIV testing experiences and their implications for patient engagement with HIV care and treatment on the eve of 'test and treat': findings from a multicountry qualitative study.

    Science.gov (United States)

    Wringe, Alison; Moshabela, Mosa; Nyamukapa, Constance; Bukenya, Dominic; Ondenge, Ken; Ddaaki, William; Wamoyi, Joyce; Seeley, Janet; Church, Kathryn; Zaba, Basia; Hosegood, Victoria; Bonnington, Oliver; Skovdal, Morten; Renju, Jenny

    2017-07-01

    In view of expanding 'test and treat' initiatives, we sought to elicit how the experience of HIV testing influenced subsequent engagement in HIV care among people diagnosed with HIV. As part of a multisite qualitative study, we conducted in-depth interviews in Uganda, South Africa, Tanzania, Kenya, Malawi and Zimbabwe with 5-10 health workers and 28-59 people living with HIV, per country. Topic guides covered patient and provider experiences of HIV testing and treatment services. Themes were derived through deductive and inductive coding. Various practices and techniques were employed by health workers to increase HIV testing uptake in line with national policies, some of which affected patients' subsequent engagement with HIV services. Provider-initiated testing was generally appreciated, but rarely considered voluntary, with instances of coercion and testing without consent, which could lead to disengagement from care.Conflicting rationalities for HIV testing between health workers and their clients caused tensions that undermined engagement in HIV care among people living with HIV. Although many health workers helped clients to accept their diagnosis and engage in care, some delivered static, morally charged messages regarding sexual behaviours and expectations of clinic use which discouraged future care seeking. Repeat testing was commonly reported, reflecting patients' doubts over the accuracy of prior results and beliefs that antiretroviral therapy may cure HIV. Repeat testing provided an opportunity to develop familiarity with clinical procedures, address concerns about HIV services and build trust with health workers. The principles of consent and confidentiality that should underlie HIV testing and counselling practices may be modified or omitted by health workers to achieve perceived public health benefits and policy expectations. While such actions can increase HIV testing rates, they may also jeopardise efforts to connect people diagnosed with HIV to

  6. Engaging black sub-Saharan African communities and their gatekeepers in HIV prevention programs: Challenges and strategies from England

    Directory of Open Access Journals (Sweden)

    Mathew Nyashanu

    2016-12-01

    Full Text Available Objective: HIV infection is a sensitive issue in black communities [Serrant-Green L. Black Caribbean men, sexual health decisions and silences. Doctoral thesis. Nottingham School of Nursing, University of Nottingham; 2004]. Statistics show black sub-Saharan African (BSSA communities disproportionately constitute two-thirds of people with HIV [Heath Protection Agency. Health protection report: latest infection reports-GOV.UK; 2013]. African communities constitute 30% of people accessing HIV treatment in the United Kingdom yet represent less than 1% of the population [Health Protection Agency. HIV in the United Kingdom: 2012 report; 2012], [Department of Health. DVD about FGM. 2012. Available from fgm@dh.gsi.gov.uk.]. This article explores the sociocultural challenges in engaging BSSA communities in HIV prevention programs in England and possible strategies to improve their involvement. Methods: Twelve focus group discussions and 24 semistructured interviews were conducted in a 2-year period with participants from the BSSA communities and sexual health services in the West Midlands, England. The research was supported by the Ubuntu scheme, a sexual health initiative working with African communities in Birmingham, England. Results: Ineffective engagement with African communities can hinder the effectiveness of HIV prevention programs. Skills and strategies sensitive to BSSA culture are important for successful implementation of prevention programs. HIV prevention programs face challenges including stigma, denial, and marginalized views within BSSA communities. Conclusion: Networking, coordination, and cultural sensitivity training for health professionals are key strategies for engaging BSSA communities in HIV prevention programs.

  7. Engaging Religious Institutions to Address Racial Disparities in HIV/AIDS: A Case of Academic-Community Partnership

    Science.gov (United States)

    Szaflarski, Magdalena; Vaughn, Lisa M.; Chambers, Camisha; Harris, Mamie; Ruffner, Andrew; Wess, Yolanda; Mosley, LaSharon; Smith, Chandra

    2017-01-01

    African Americans face the most severe burden of HIV among all racial and ethnic groups. Direct involvement of faith leaders and faith communities is increasingly suggested as a primary strategy to reduce HIV-related disparities, and Black churches are uniquely positioned to address HIV stigma, prevention, and care in African American communities. The authors describe an academic-community partnership to engage Black churches to address HIV in a predominantly African American, urban, southern Midwest location. The opportunities, process, and challenges in forming this academic-community partnership with Black churches can be used to guide future efforts toward engaging faith institutions, academia, and other community partners in the fight against HIV. PMID:28239643

  8. Addressing gender dynamics and engaging men in HIV programs: lessons learned from Horizons research.

    Science.gov (United States)

    Pulerwitz, Julie; Michaelis, Annie; Verma, Ravi; Weiss, Ellen

    2010-01-01

    In the field of human immunodeficiency virus (HIV) prevention, there has been increasing interest in the role that gender plays in HIV and violence risk, and in successfully engaging men in the response. This article highlights findings from more than 10 studies in Asia, Africa, and Latin America--conducted from 1997 through 2007 as part of the Horizons program--that have contributed to understanding the relationship between gender and men's behaviors, developing useful measurement tools for gender norms, and designing and evaluating the impact of gender-focused program strategies. Studies showed significant associations between support for inequitable norms and risk, such as more partner violence and less condom use. Programmatic lessons learned ranged from insights into appropriate media messages, to strategies to engage men in critically reflecting upon gender inequality, to the qualities of successful program facilitators. The portfolio of work reveals the potential and importance of directly addressing gender dynamics in HIV- and violence-prevention programs for both men and women.

  9. Social Networking Technology Use and Engagement in HIV Related Risk and Protective Behaviors among Homeless Youth

    Science.gov (United States)

    Barman-Adhikari, Anamika; Rice, Eric; Bender, Kimberly; Lengnick-Hall, Rebecca; Yoshioka-Maxwell, Amanda; Rhoades, Harmony

    2016-01-01

    Preliminary studies with homeless youth find surprisingly pervasive social media use and suggest youths’ online interactions may be associated with their HIV-related risk and protective behaviors. As homeless youth are transient and difficult to engage in place-based services, social media may represent a novel venue for intervention. A critical first step in intervention development is gaining greater understanding of how homeless youth use social media especially as it relates to whom they connect to and around what topics. Given the salience of Social Networking Sites in the lives of these otherwise difficult to reach adolescents, and their potential to disseminate prevention interventions, this study assessed associations between online social networking technology use and HIV risk behaviors among homeless youth in Los Angeles, California. Homeless youth ages 13 through 24 (N=1046) were recruited through three drop-in centers and surveyed about their social media use and self-reported HIV-related risk behaviors. Results suggest that social media use is widely prevalent among this population, and the content of these online interactions is associated with whether or not they engage in risk or protective behaviors. Implications for interventions and further research are discussed. PMID:27337044

  10. Suicidal Ideation Persists Among Individuals Engaged in HIV Care in the Era of Antiretroviral Therapy.

    Science.gov (United States)

    López, J D; Shacham, E; Brown, T

    2017-01-06

    Little research has focused on suicidality in the era of successful antiretroviral therapy among those engaged in HIV care. We performed a study of 648 clinic patients who completed a psychological and behavioral annual assessment in 2012. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9), suicidal ideation was measured by the last item of the scale. Anxiety symptoms were measured using the Generalized Anxiety Disorder-7 questionnaire (GAD-7). HIV biomedical markers were abstracted from medical records. Suicidal ideation was reported among 13% (n = 81) of the sample. Individuals endorsing suicidality were more likely to have unsuppressed viral loads, moderate to severe anxiety symptoms and consider themselves to be homeless (p < 0.01 for all). After adjusting for confounders, homeless individuals and those endorsing moderate to severe anxiety symptoms had higher odds of reporting suicidality. Results suggest basic needs must be met to complement HIV management efforts. Furthermore, better understanding of how psychological distress symptoms are expressed and how to manage them may better inform barriers to HIV management.

  11. At the coalface and the cutting edge: general practitioners' accounts of the rewards of engaging with HIV medicine.

    Science.gov (United States)

    Newman, Christy E; Persson, Asha; de Wit, John B F; Reynolds, Robert H; Canavan, Peter G; Kippax, Susan C; Kidd, Michael R

    2013-03-21

    HIV has become a chronic manageable infection in the developed world, and early and lifelong treatment has the potential to significantly reduce transmission rates in the community. A skilled and motivated HIV medical workforce will be required to achieve these health management and prevention outcomes, but concerns have been noted in a number of settings about the challenges of recruiting a new generation of clinicians to HIV medicine. As part of a larger qualitative study of the HIV general practice workforce in Australia, in-depth interviews were conducted with 31 general practitioners accredited to prescribe HIV medications in community settings. A thematic analysis was conducted of the de-identified transcripts, and this paper describes and interprets accounts of the rewards of pursuing and sustaining an engagement with HIV medicine in general practice settings. The rewards of initially becoming involved in providing care to people living with HIV were described as interest and inspiration, community calling and right place, right time. The rewards which then supported and sustained that engagement over time were described as challenge and change, making a difference and enhanced professional identity. Participants viewed the role of primary care doctor with special expertise in HIV as occupying an ideal interface between the 'coalface' and the 'cutting edge', and offering a unique opportunity for general practitioners to feel intimately connected to both community needs and scientific change. Approaches to recruiting and retaining the HIV medical workforce should build upon the intellectual and social rewards of this work, as well as the sense of professional belonging and connection which is imbued between both doctors and patients and across the global and national networks of HIV clinicians. Insights regarding the rewards of engaging with HIV medicine may also be useful in enhancing the prospect of general practice as a career, and strengthening retention

  12. Correlation of Internet Use for Health Care Engagement Purposes and HIV Clinical Outcomes Among HIV-Positive Individuals Using Online Social Media.

    Science.gov (United States)

    Saberi, Parya; Johnson, Mallory O

    2015-01-01

    The authors aimed to describe cell phone and Internet use and assess the correlation of Internet use for health care engagement purposes and HIV clinical outcomes among HIV-positive individuals. The authors conducted a national survey using online social media to examine cell phone and Internet use, self-reported HIV viral load (detectable vs. undetectable), and antiretroviral adherence rating (excellent vs. less than excellent). Participants (N = 1,494) were asked about their Internet use for health care engagement purposes (including e-mailing health care providers, refilling medications online, and making medical appointments online). Approximately 95% of participants accessed the Internet nearly daily or daily in the past month (mean hours on Internet use per day = 5.2) and 55.5% used the Internet for health care engagement purposes. Those who used the Internet for any health care engagement purposes had a 1.52-fold odds of reporting an undetectable viral load (p = .009) and a 1.49-fold odds of reporting excellent adherence (p = .001). Although Internet access and use were similar across racial/ethnic, educational, and socioeconomic groups, disparities existed with the use of the Internet for health care engagement purposes among racial/ethnic minorities, those with low to moderate financial stability, lower education, and history of incarceration. The authors' data reveal that among HIV-positive users of online social media, use of the Internet for health care engagement purposes is associated with better self-reported virologic and adherence outcomes.

  13. Understanding Care Linkage and Engagement Across 15 Adolescent Clinics: Provider Perspectives and Implications for Newly HIV-Infected Youth.

    Science.gov (United States)

    Philbin, Morgan M; Tanner, Amanda E; DuVal, Anna; Ellen, Jonathan M; Kapogiannis, Bill; Fortenberry, J Dennis

    2017-04-01

    The National HIV/AIDS Strategy emphasizes rapid care linkage and engagement for HIV-infected individuals, though many adolescents are never tested, delay entering care, and frequently drop out. We conducted 183 staff interviews at 15 adolescent medicine clinics (baseline, n = 64; Year 1, n = 60; Year 2, = 59). We used a constant comparative thematic method to examine how providers approached and discussed care linkage/engagement. Qualitative analyses revealed differences in providers' conceptualizations of linkage and engagement. Providers saw linkage as mechanistic and health system driven. It was defined by number of clinic visits and involved relatively little youth agency. In contrast, providers defined engagement by youths' responsibility and participation in their own care. Linkage and engagement are related but distinct aspects of care that require different resources and levels of staff involvement. Integrating an understanding of these differences into future interventions will allow clinic staff to help youth improve long-term health outcomes.

  14. Multi-level factors affecting entry into and engagement in the HIV continuum of care in Iringa, Tanzania.

    Science.gov (United States)

    Layer, Erica H; Kennedy, Caitlin E; Beckham, Sarah W; Mbwambo, Jessie K; Likindikoki, Samuel; Davis, Wendy W; Kerrigan, Deanna L; Brahmbhatt, Heena

    2014-01-01

    Progression through the HIV continuum of care, from HIV testing to lifelong retention in antiretroviral therapy (ART) care and treatment programs, is critical to the success of HIV treatment and prevention efforts. However, significant losses occur at each stage of the continuum and little is known about contextual factors contributing to disengagement at these stages. This study sought to explore multi-level barriers and facilitators influencing entry into and engagement in the continuum of care in Iringa, Tanzania. We used a mixed-methods study design including facility-based assessments and interviews with providers and clients of HIV testing and treatment services; interviews, focus group discussions and observations with community-based providers and clients of HIV care and support services; and longitudinal interviews with men and women living with HIV to understand their trajectories in care. Data were analyzed using narrative analysis to identify key themes across levels and stages in the continuum of care. Participants identified multiple compounding barriers to progression through the continuum of care at the individual, facility, community and structural levels. Key barriers included the reluctance to engage in HIV services while healthy, rigid clinic policies, disrespectful treatment from service providers, stock-outs of supplies, stigma and discrimination, alternate healing systems, distance to health facilities and poverty. Social support from family, friends or support groups, home-based care providers, income generating opportunities and community mobilization activities facilitated engagement throughout the HIV continuum. Findings highlight the complex, multi-dimensional dynamics that individuals experience throughout the continuum of care and underscore the importance of a holistic and multi-level perspective to understand this process. Addressing barriers at each level is important to promoting increased engagement throughout the continuum.

  15. The Global Engagement in Care Convening: Recommended Actions to Improve Health Outcomes for People Living With HIV.

    Science.gov (United States)

    Maulsby, C; Valdiserri, R O; Kim, J J; Mahon, N; Flynn, A; Eriksson, E; Jain, K M; Enobun, Blessing; Holtgrave, D R

    2016-10-01

    The National HIV AIDS Strategy (NHAS) calls for a more coordinated response to the HIV epidemic. The Global Engagement in Care Convening created a forum for domestic and international experts to identify best practices in HIV care. This manuscript summarizes the meeting discussions and recommendations from meeting notes and an audio recording of the meeting. Recommendations include: further standardization of performance goals and performance measures; additional research; a more robust system to support competing needs of clients receiving services; electronic information exchanges for HIV-related data; an expansion of the role of other health professionals to extend the capacity of physicians and other members of the care team; and revisions to current financing systems to increase reimbursement for and access to services that promote linkage to and retention in HIV care. The recommendations provide a unique example of "reverse technical assistance" and will inform U.S. program development, research, and policy.

  16. Patient-Provider Engagement and Chronic Pain in Drug-Using, Primarily African American Persons Living with HIV/AIDS.

    Science.gov (United States)

    Mitchell, Mary M; Nguyen, Trang Q; Maragh-Bass, Allysha C; Isenberg, Sarina R; Beach, Mary Catherine; Knowlton, Amy R

    2017-06-01

    Among disadvantaged persons living with HIV/AIDS (PLHIV), patient-provider engagement, which has been defined as patient-provider relationships that promote the use of health care services and are characterized by active listening and supportive decision making, has been associated with antiretroviral therapy (ART) maintenance and viral suppression. However, chronic pain, depression, and substance use, all of which are prevalent in this population, can reduce the quality of patient-provider engagement. We hypothesized a model in which chronic pain, depression, and substance use would be associated with poorer patient-provider engagement, which would be positively associated with adherence, with the latter associated positively with viral suppression. We analyzed data from the BEACON study, which included surveys from 383 PLHIV who were primarily African American, on ART, and had histories of drug use. Due to six missing cases on the chronic pain variable, we used data from 377 respondents in a structural equation model. Chronic pain and depressive symptoms were significantly associated with poorer patient-provider engagement, while substance use was associated with better engagement. Patient-provider engagement in turn was associated with better ART adherence, which was associated with higher viral suppression. Results suggest the role of chronic pain in poor patient-physician engagement in this population, which has potential implications for quality of HIV patient care and health outcomes. Findings suggest the need for attention to patient-provider engagement in PLHIV.

  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. A Role for Small Antibody Fragments to Bind and Neutralize HIV | Center for Cancer Research

    Science.gov (United States)

    The surface of the Human Immunodeficiency Virus (HIV) is studded with numerous copies of the glycoprotein Env. Each Env spike is composed of three copies of the proteins gp41, which sits in the viral membrane, and gp120, which rests on top of each gp41 molecule. Env is essential for HIV-mediated infection because the binding of gp120 to the T cell surface receptor CD4 initiates a conformational change in Env exposing the fusion peptide, which inserts into the T cell membrane and helps fuse the T cell and virus together. This makes Env an attractive target for designing therapeutic inhibitory antibodies. However, the complexities of the HIV surface proteins and the tight association of the virus and T cell during infection have hampered the identification of full-length antibodies with effective HIV neutralizing activity.

  19. Disengagement and Engagement Coping with HIV/AIDS Stigma and Psychological Well-Being of People with HIV/AIDS

    OpenAIRE

    Varni, Susan E.; Miller, Carol T.; McCuin, Tara; Solomon, Sondra E.

    2012-01-01

    The stigma associated with HIV/AIDS poses a psychological challenge to people living with HIV/AIDS. We hypothesized that that the consequences of stigma-related stressors on psychological well-being would depend on how people cope with the stress of HIV/AIDS stigma. Two hundred participants with HIV/AIDS completed a self-report measure of enacted stigma and felt stigma, a measure of how they coped with HIV/AIDS stigma, and measures of depression and anxiety, and self-esteem. In general, incre...

  20. Identification of homologous regions in human immunodeficiency virus I gp41 and human MHC class II beta 1 domain. I. Monoclonal antibodies against the gp41-derived peptide and patients' sera react with native HLA class II antigens, suggesting a role for autoimmunity in the pathogenesis of acquired immune deficiency syndrome.

    Science.gov (United States)

    Golding, H; Robey, F A; Gates, F T; Linder, W; Beining, P R; Hoffman, T; Golding, B

    1988-03-01

    Homologous regions of five amino acids each, were identified in the NH2-terminal domain of human class II beta chains and the COOH terminus of HIV I envelope protein. The homologous regions are highly conserved among different DR and DQ alleles and also among different isolates of HIV. Septamers containing these sequences were synthesized and used for the generation of murine mAbs. The mAbs selected for this study were raised against the HIV I-derived peptide and reacted strongly not only with the immunizing peptide, but also with the homologous class II-derived peptide. These mAbs also reacted with native MHC class II antigens expressed on human B cell lines and on murine fibroblast L cell lines transfected with the genes coding for the alpha and beta chains of human class II antigens. Furthermore, sera from 36% of AIDS patients tested contained antibodies that reacted with the class II-derived peptide, as well as with intact class II molecule-rich cell extracts. Such antibodies in HIV I-infected individuals may recognize self class II antigens, triggering autoimmune mechanisms that could contribute to the development of immunodeficiency in AIDS patients.

  1. Community engagement in sexual health and uptake of HIV testing and syphilis testing among MSM in China: a cross-sectional online survey.

    Science.gov (United States)

    Zhang, Tiange P; Liu, Chuncheng; Han, Larry; Tang, Weiming; Mao, Jessica; Wong, Terrence; Zhang, Ye; Tang, Songyuan; Yang, Bin; Wei, Chongyi; Tucker, Joseph D

    2017-04-03

    HIV and syphilis testing rates remain low among men who have sex with men (MSM) in low- and middle-income countries (LMICs). Community engagement has been increasingly used to promote HIV testing among key populations in high-income countries, often in settings with stronger civil society. This study aimed to assess socio-demographic, behavioural, and community engagement factors associated with HIV and syphilis testing among MSM in China. MSM ≥16 years old who had condomless sex in the past three months were recruited nationwide to complete a cross-sectional online survey in November 2015. Data were collected on socio-demographics, sexual behaviours, HIV testing, syphilis testing, and community engagement in sexual health. We defined community engagement in sexual health using six items assessing awareness and advocacy of sexual health programmes. The underlying factor structure of a 6-item community engagement scale was determined through exploratory factor analysis. Univariate and multivariable logistic regressions identified correlates of HIV and syphilis testing. 1189 MSM were recruited. 54% (647/1189) of men had ever tested for HIV and 30% (354/1189) had ever tested for syphilis. Factor analysis suggested three levels of community engagement (minimal, moderate, and substantial) and this model explained 79.5% of observed variance. A quarter (26%, 312/1189) reported none to minimal engagement, over one half (54%, 644/1189) reported moderate engagement, and a fifth (20%, 233/1189) reported substantial engagement. Multivariable logistic regression showed that MSM with greater community engagement in sexual health were more likely to have ever tested for HIV (substantial vs. no engagement: aOR 7.91, 95% CI 4.98-12.57) and for syphilis (substantial vs. no engagement: aOR 5.35, 95% CI 3.16-9.04). HIV and syphilis testing are suboptimal among MSM in China. Community engagement may be useful for promoting testing in China and should be considered in intervention

  2. Engaging African and Caribbean Immigrants in HIV Testing and Care in a Large US City: Lessons Learned from the African Diaspora Health Initiative.

    Science.gov (United States)

    Kwakwa, Helena A; Wahome, Rahab; Goines, Djalika S; Jabateh, Voffee; Green, Arraina; Bessias, Sophia; Flanigan, Timothy P

    2017-08-01

    The lifting in 2010 of the HIV entry ban eliminated an access point for HIV testing of the foreign-born. The African Diaspora Health Initiative (ADHI) was developed to examine alternative pathways to testing for African and Caribbean persons. The ADHI consists of Clinics Without Walls (CWW) held in community settings. HIV testing is offered to participants along with hypertension and diabetes screening. A survey is administered to participants. Descriptive data were analyzed using SAS 9.2. Between 2011 and 2015, 4152 African and Caribbean individuals participated in 352 CWW. Participants were mostly (67.7 %) African. HIV rates were lowest in Caribbean women (0.4 %) and highest in Caribbean men (8.4 %). Efforts to engage African and Caribbean communities in HIV testing are important given the elimination of the HIV entry ban and continued immigration to the US from areas of higher prevalence. The ADHI offers a successful model of engagement.

  3. Growing the Pipeline of Diverse HIV Investigators: The Impact of Mentored Research Experiences to Engage Underrepresented Minority Students.

    Science.gov (United States)

    Fuchs, Jonathan; Kouyate, Aminta; Kroboth, Liz; McFarland, Willi

    2016-09-01

    Structured, mentored research programs for high school and undergraduate students from underrepresented minority (URM) backgrounds are needed to increase the diversity of our nation's biomedical research workforce. In particular, a robust pipeline of investigators from the communities disproportionately affected by the HIV epidemic is needed not only for fairness and equity but for insights and innovations to address persistent racial and ethnic disparities in new infections. We created the Summer HIV/AIDS Research Program (SHARP) at the San Francisco Department of Public Health for URM undergraduates as a 12-week program of hands-on research experience, one-on-one mentoring by a senior HIV investigator, didactic seminars for content and research methods, and networking opportunities. The first four cohorts (2012-2015) of SHARP gained research skills, built confidence in their abilities and self-identified as scientists. In addition, the majority of program alumni is employed in research positions and has been admitted to or is pursuing graduate degree programs in fields related to HIV prevention. While we await empirical studies of specific mentoring strategies at early educational stages, programs that engage faculty who are sensitive to the unique challenges facing diverse students and who draw lessons from established mentoring frameworks can help build an inclusive generation of HIV researchers.

  4. Motivational Interviewing among HIV Health Care Providers: Challenges and opportunities to enhance engagement and retention in care in Buenos Aires, Argentina

    Science.gov (United States)

    Bofill, Lina; Weiss, Stephen M; Lucas, Mar; Bordato, Alejandra; Dorigo, Analia; Fernandez-Cabanillas, Graciela; Aristegui, Ines; Lopez, Maria; Waldrop-Valverde, Drenna; Jones, Deborah

    2016-01-01

    Providers’ response to Motivational Interviewing (MI) to improve engagement and retention in care among challenging patients with HIV in Argentina were evaluated. 12 HIV care physicians participated and video recordings pre- and post-MI training were obtained. One week post-training 11/12 participants were committed to using MI strategies during consult session. 9/12 participants demonstrated appropriate utilization of MI techniques and increased adherence focused discussion and care (t = 3.59, p = .006). MI appears to be a viable strategy to enhance engagement and retention in challenging HIV patients. PMID:26056148

  5. Towards a Science of Community Stakeholder Engagement in Biomedical HIV Prevention Trials: An Embedded Four-Country Case Study.

    Directory of Open Access Journals (Sweden)

    Peter A Newman

    Full Text Available Broad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations.From 2008-2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement.Across settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of "community"; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted.This multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as

  6. Towards a Science of Community Stakeholder Engagement in Biomedical HIV Prevention Trials: An Embedded Four-Country Case Study.

    Science.gov (United States)

    Newman, Peter A; Rubincam, Clara; Slack, Catherine; Essack, Zaynab; Chakrapani, Venkatesan; Chuang, Deng-Min; Tepjan, Suchon; Shunmugam, Murali; Roungprakhon, Surachet; Logie, Carmen; Koen, Jennifer; Lindegger, Graham

    2015-01-01

    Broad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations. From 2008-2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement. Across settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of "community"; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted. This multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as highlighting

  7. Isotype modulates epitope specificity, affinity, and antiviral activities of anti-HIV-1 human broadly neutralizing 2F5 antibody.

    Science.gov (United States)

    Tudor, Daniela; Yu, Huifeng; Maupetit, Julien; Drillet, Anne-Sophie; Bouceba, Tahar; Schwartz-Cornil, Isabelle; Lopalco, Lucia; Tuffery, Pierre; Bomsel, Morgane

    2012-07-31

    The constant heavy chain (CH1) domain affects antibody affinity and fine specificity, challenging the paradigm that only variable regions contribute to antigen binding. To investigate the role of the CH1 domain, we constructed IgA2 from the broadly neutralizing anti-HIV-1 2F5 IgG1, and compared 2F5 IgA2 and IgG binding affinity and functional activities. We found that 2F5 IgA2 bound to the gp41 membrane proximal external region with higher affinity than IgG1. Functionally, compared with IgG1, 2F5 IgA2 more efficiently blocked HIV-1 transcytosis across epithelial cells and CD4(+) cell infection by R5 HIV-1. The 2F5 IgG1 and IgA2 acted synergistically to fully block HIV-1 transfer from Langerhans to autologous CD4(+) T cells and to inhibit CD4(+) T-cell infection. Epitope mapping performed by screening a random peptide library and in silico docking modeling suggested that along with the 2F5 IgG canonical ELDKWA epitope on gp41, the IgG1 recognized an additional 3D-conformational epitope on the gp41 C-helix. In contrast, the IgA2 epitope included a unique conformational motif on the gp41 N-helix. Overall, the CH1 region of 2F5 contributes to shape its epitope specificity, antibody affinity, and functional activities. In the context of sexually transmitted infections such as HIV-1/AIDS, raising a mucosal IgA-based vaccine response should complement an IgG-based vaccine response in blocking HIV-1 transmission.

  8. Isotype modulates epitope specificity, affinity, and antiviral activities of anti–HIV-1 human broadly neutralizing 2F5 antibody

    Science.gov (United States)

    Tudor, Daniela; Yu, Huifeng; Maupetit, Julien; Drillet, Anne-Sophie; Bouceba, Tahar; Schwartz-Cornil, Isabelle; Lopalco, Lucia; Tuffery, Pierre; Bomsel, Morgane

    2012-01-01

    The constant heavy chain (CH1) domain affects antibody affinity and fine specificity, challenging the paradigm that only variable regions contribute to antigen binding. To investigate the role of the CH1 domain, we constructed IgA2 from the broadly neutralizing anti–HIV-1 2F5 IgG1, and compared 2F5 IgA2 and IgG binding affinity and functional activities. We found that 2F5 IgA2 bound to the gp41 membrane proximal external region with higher affinity than IgG1. Functionally, compared with IgG1, 2F5 IgA2 more efficiently blocked HIV-1 transcytosis across epithelial cells and CD4+ cell infection by R5 HIV-1. The 2F5 IgG1 and IgA2 acted synergistically to fully block HIV-1 transfer from Langerhans to autologous CD4+ T cells and to inhibit CD4+ T-cell infection. Epitope mapping performed by screening a random peptide library and in silico docking modeling suggested that along with the 2F5 IgG canonical ELDKWA epitope on gp41, the IgG1 recognized an additional 3D-conformational epitope on the gp41 C-helix. In contrast, the IgA2 epitope included a unique conformational motif on the gp41 N-helix. Overall, the CH1 region of 2F5 contributes to shape its epitope specificity, antibody affinity, and functional activities. In the context of sexually transmitted infections such as HIV-1/AIDS, raising a mucosal IgA-based vaccine response should complement an IgG-based vaccine response in blocking HIV-1 transmission. PMID:22723360

  9. Social Networking Technology Use and Engagement in HIV-Related Risk and Protective Behaviors Among Homeless Youth.

    Science.gov (United States)

    Barman-Adhikari, Anamika; Rice, Eric; Bender, Kimberly; Lengnick-Hall, Rebecca; Yoshioka-Maxwell, Amanda; Rhoades, Harmony

    2016-07-01

    Preliminary studies with homeless youth have found surprisingly pervasive social media use and suggest that youth's online interactions may be associated with their HIV-related risk and protective behaviors. As homeless youth are transient and difficult to engage in place-based services, social media may represent a novel venue for intervention. A critical 1st step in intervention development is gaining greater understanding of how homeless youth use social media, especially as it relates to who they connect to and around what topics. Given the salience of social networking sites in the lives of these otherwise difficult-to-reach adolescents, and their potential to disseminate prevention interventions, this study assessed associations between online social networking technology use and HIV risk behaviors among homeless youth in Los Angeles, California. Homeless youth ages 13 through 24 (N = 1,046) were recruited through 3 drop-in centers and surveyed about their social media use and self-reported HIV-related risk behaviors. Results suggest that social media use is widely prevalent among this population, and the content of these online interactions is associated with whether youth engage in risk or protective behaviors. Implications for interventions and further research are discussed.

  10. HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

    Directory of Open Access Journals (Sweden)

    Kelly E Seaton

    Full Text Available Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

  11. Recombinant envelope protein of HIV-1 subtype E as antigen in HIV-1 antibody detection enzyme immunoassay.

    Science.gov (United States)

    Sutthent, Ruengpung; Kanoksinsombat, Chinda; Horthongkham, Navin; Louisirirotchanakul, Suda; Auewarakul, Prasert; Kantakamalakul, Wannee

    2002-06-01

    In order to develop a reliable and inexpensive serodiagnostic method to be used for anti-HIV antibody detection in Thailand, recombinant envelope (TM or gp41 subunit) protein of HIV-1 subtype E was produced from prokaryotic cell (Escherichia coli) as the source of antigen in enzyme immunoassay (TE diagnostic EIA kit). HIV-1 gp41 subunit of subtype E was successfully expressed in E. coli in the form of polyhistidine-tagged proteins, comprising of rgp41A (601 bases N-terminal half of TM or 25kDa) and rgp41B (560 bases C-terminal half of TM or 24 kDa) by using an expression vector, pBAD/His C. The amount of protein, dilution of sera, and anti-human IgG labeled HRP used in the EIA test optimized by a checker board titration of the protein and seropositive or seronegative sera, were 5.0 microg/ml, 1:300, and 1:4,000, respectively. The blinded test evaluation of TE-diagnostic EIA in 500 seropositive and 500 seronegative sera which have been simultaneously tested by two available commercial kits and compared with our TE diagnostic EIA, gave 99.6% sensitivity and specificity. The other known genetic subtypes sera such as subtype A (n=5), B (n=9), C (n=4) and D (n=5) were also positive with this EIA. The estimated manufacturer cost per test of rgp41 based anti-HIV antibody detection EIA or TE-diagnostic EIA was about 15 baht. This recombinant envelope (gp41 or TM) protein from HIV-1, which can be produced in large quantities without any hazards from growing the virus and has lower cost to produce anti-HIV antibody serological diagnostic kit, should be considered as an HIV screening test in Thailand.

  12. Evaluating the effects of community-based organization engagement on HIV and AIDS-related risk behavior in Kenya.

    Science.gov (United States)

    Riehman, Kara S; Kakietek, Jakub; Manteuffel, Brigitte A; Rodriguez-García, Rosalía; Bonnel, Rene; N'Jie, N'Della; Godoy-Garraza, Lucas; Orago, Alloys; Murithi, Patrick; Fruh, Joseph

    2013-01-01

    International donors have increasingly shifted AIDS funding directly to community-based organizations (CBOs) with the assumption that responding to the epidemic is best achieved at the community level. The World Bank, ICF Macro, and the National Council for Population and Development in Kenya, conducted a study to evaluate the community response in Kenya. The study used a quasi-experimental design comparing seven study communities and seven comparison communities in Nyanza Province and Western Province. We examined the impact of CBO activity on individual and community-level outcomes, including HIV knowledge, awareness and perceptions, sexual risk behavior, and social transformation (gender ideology and social capital). The study consisted of two components: a household survey conducted in all 14 communities, and qualitative data collected in a subset of communities. Individuals in communities with higher CBO engagement were significantly more likely to have reported consistent condom use. Higher CBO engagement was associated with some measures of social capital, including participation in local and national elections, and participation in electoral campaigns. CBOs provide added value in addressing the HIV and AIDS epidemic in very targeted and specific ways that are closely tied to the services they provide (e.g., prevention education); thus, increasing CBO engagement can be an effective measure in scaling up prevention efforts in those areas.

  13. “Facing Our Fears”: Using facilitated film viewings to engage communities in HIV research involving MSM in Kenya

    Science.gov (United States)

    Kombo, Bernadette; Sariola, Salla; Gichuru, Evanson; Molyneux, Sassy; Sanders, Eduard J.; van der Elst, Elise

    2017-01-01

    Abstract Kenya is a generally homophobic country where homosexuality is criminalised and people who engage in same sex sexuality face stigma and discrimination. In 2013, we developed a 16 min documentary entitled “Facing Our Fears” that aimed at sharing information on how and why men who have sex with men (MSM) are involved in on-going KEMRI HIV prevention research, and associated community engagement. To consider the film’s usefulness as a communication tool, and its perceived security risks in case the film was publicly released, we conducted nine facilitated viewings with 122 individuals representing seven different stakeholder groups. The documentary was seen as a strong visual communication tool with potential to reduce stigma related to homosexuality, and facilitated film viewings were identified as platforms with potential to support open dialogue about HIV research involving MSM. Despite the potential, there were concerns over possible risks to LGBT communities and those working with them following public release. We opted—giving emphasis to the “do no harm” principle—to use the film only in facilitated settings where audience knowledge and attitudes can be carefully considered and discussed. The results highlight the importance of carefully assessing the range of possible impacts when using visuals in community engagement. PMID:28670602

  14. "Facing Our Fears": Using facilitated film viewings to engage communities in HIV research involving MSM in Kenya.

    Science.gov (United States)

    Kombo, Bernadette; Sariola, Salla; Gichuru, Evanson; Molyneux, Sassy; Sanders, Eduard J; van der Elst, Elise

    2017-01-01

    Kenya is a generally homophobic country where homosexuality is criminalised and people who engage in same sex sexuality face stigma and discrimination. In 2013, we developed a 16 min documentary entitled "Facing Our Fears" that aimed at sharing information on how and why men who have sex with men (MSM) are involved in on-going KEMRI HIV prevention research, and associated community engagement. To consider the film's usefulness as a communication tool, and its perceived security risks in case the film was publicly released, we conducted nine facilitated viewings with 122 individuals representing seven different stakeholder groups. The documentary was seen as a strong visual communication tool with potential to reduce stigma related to homosexuality, and facilitated film viewings were identified as platforms with potential to support open dialogue about HIV research involving MSM. Despite the potential, there were concerns over possible risks to LGBT communities and those working with them following public release. We opted-giving emphasis to the "do no harm" principle-to use the film only in facilitated settings where audience knowledge and attitudes can be carefully considered and discussed. The results highlight the importance of carefully assessing the range of possible impacts when using visuals in community engagement.

  15. Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy

    Directory of Open Access Journals (Sweden)

    Kliger Yossef

    2003-09-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS is a febrile respiratory illness. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus (SARS-CoV, whose genome was recently sequenced. Since it is a member of the Coronaviridae, its spike protein (S2 is believed to play a central role in viral entry by facilitating fusion between the viral and host cell membranes. The protein responsible for viral-induced membrane fusion of HIV-1 (gp41 differs in length, and has no sequence homology with S2. Results Sequence analysis reveals that the two viral proteins share the sequence motifs that construct their active conformation. These include (1 an N-terminal leucine/isoleucine zipper-like sequence, and (2 a C-terminal heptad repeat located upstream of (3 an aromatic residue-rich region juxtaposed to the (4 transmembrane segment. Conclusions This study points to a similar mode of action for the two viral proteins, suggesting that anti-viral strategy that targets the viral-induced membrane fusion step can be adopted from HIV-1 to SARS-CoV. Recently the FDA approved Enfuvirtide, a synthetic peptide corresponding to the C-terminal heptad repeat of HIV-1 gp41, as an anti-AIDS agent. Enfuvirtide and C34, another anti HIV-1 peptide, exert their inhibitory activity by binding to a leucine/isoleucine zipper-like sequence in gp41, thus inhibiting a conformational change of gp41 required for its activation. We suggest that peptides corresponding to the C-terminal heptad repeat of the S2 protein may serve as inhibitors for SARS-CoV entry.

  16. HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation.

    Science.gov (United States)

    Henrick, Bethany M; Yao, Xiao-Dan; Rosenthal, Kenneth Lee

    2015-01-01

    Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2) physically inhibited HIV-induced NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs) for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2). Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41, act as viral PAMPs signaling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development.

  17. Frequency of human immunodeficiency virus type-2 in hiv infected patients in Maputo City, Mozambique

    Directory of Open Access Journals (Sweden)

    Bhatt Nilesh

    2011-08-01

    Full Text Available Abstract The HIV/AIDS pandemic is primarily caused by HIV-1. Another virus type, HIV-2, is found mainly in West African countries. We hypothesized that population migration and mobility in Africa may have facilitated the introduction and spreading of HIV-2 in Mozambique. The presence of HIV-2 has important implications for diagnosis and choice of treatment of HIV infection. Hence, the aim of this study was to estimate the prevalence of HIV-2 infection and its genotype in Maputo, Mozambique. HIV-infected individuals (N = 1,200 were consecutively enrolled and screened for IgG antibodies against HIV-1 gp41 and HIV-2 gp36 using peptide-based enzyme immunoassays (pepEIA. Specimens showing reactivity on the HIV-2 pepEIA were further tested using the INNO-LIA immunoblot assay and HIV-2 PCR targeting RT and PR genes. Subtype analysis of HIV-2 was based on the protease gene. After screening with HIV-2 pepEIA 1,168 were non-reactive and 32 were reactive to HIV-2 gp36 peptide. Of this total, 30 specimens were simultaneously reactive to gp41 and gp36 pepEIA while two samples reacted solely to gp36 peptide. Only three specimens containing antibodies against gp36 and gp105 on the INNO-LIA immunoblot assay were found to be positive by PCR to HIV-2 subtype A. The proportion of HIV-2 in Maputo City was 0.25% (90%CI 0.01-0.49. The HIV epidemic in Southern Mozambique is driven by HIV-1, with HIV-2 also circulating at a marginal rate. Surveillance program need to improve HIV-2 diagnosis and consider periodical survey aiming to monitor HIV-2 prevalence in the country.

  18. Stable incidence of HIV diagnoses among Danish MSM despite increased engagement in unsafe sex

    DEFF Research Database (Denmark)

    Cowan, Susan Alice; Gerstoft, Jan; Haff, Jakob

    2012-01-01

    Since introduction of highly active antiretroviral therapy (HAART), the prevalence of Danish HIV-positive men who have sex with men (MSM) has increased substantially. In contrast, the incidence of MSM diagnosed with HIV has not increased, and this paradox has been the focus of intensive debate....

  19. Cost-Utility Analysis of Three U.S. HIV Linkage and Re-engagement in Care Programs from Positive Charge.

    Science.gov (United States)

    Jain, Kriti M; Zulliger, Rose; Maulsby, Cathy; Kim, Jeeyon Janet; Charles, Vignetta; Riordan, Maura; Holtgrave, David

    2016-05-01

    Linking and retaining people living with HIV in ongoing, HIV medical care is vital for ending the U.S. HIV epidemic. Yet, 41-44 % of HIV+ individuals are out of care. In response, AIDS United initiated Positive Charge, a series of five HIV linkage and re-engagement projects around the U.S. This paper investigates whether three Positive Charge programs were cost effective and calculates a return on investment for each program. It uses standard methods of cost utility analysis and WHO-CHOICE thresholds. All three projects were found to be cost effective, and two were highly cost effective. Cost utility ratios ranged from $4439 to $137,271. These results suggest that HIV linkage to care programs are a productive and efficient use of public health funds.

  20. Real-World Strategies to Engage and Retain Racial-Ethnic Minority Young Men Who Have Sex with Men in HIV Prevention Services.

    Science.gov (United States)

    Freese, Thomas E; Padwa, Howard; Oeser, Brandy T; Rutkowski, Beth A; Schulte, Marya T

    2017-06-01

    Racial/ethnic minority young men who have sex with men (YMSM)-particularly African Americans and Hispanics/Latinos-are at particularly high risk for HIV infection. Devising strategies to improve engagement and retention in HIV prevention services among minority YMSM is critical if the United States is going to achieve the National HIV/AIDS Strategy goal of reducing HIV health-related disparities. This article presents findings from a national summit on racial/ethnic YMSM services convened by the Substance Abuse and Mental Health Services Administration-funded Center of Excellence on Racial and Ethnic Minority Young Men Who Have Sex with Men and Other Lesbian, Gay, Bisexual, and Transgender Populations (YMSM + LGBT CoE) in September 2015. The summit included (1) subgroup discussions focused on issues related to treatment access, outreach/engagement/retention, continuing care/recovery support, and health literacy for minority YMSM; and (2) a ranking process, where the NIATx Nominal Group Technique was used to identify the strategies and approaches that summit participants believed to be most promising for engaging and retaining minority YMSM in HIV prevention services. Analyses of results from summit activities highlight four key cross-cutting strategies-utilizing peers, providing holistic care, making services fun, and utilizing technology-as critical for engaging minority YMSM in HIV prevention care. Examples of programs that utilize these strategies and implications of these findings for policy and practice are discussed.

  1. Exploring the membrane fusion mechanism through force-induced disassembly of HIV-1 six-helix bundle

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Kai [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Yong [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Lou, Jizhong, E-mail: jlou@ibp.ac.cn [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2016-05-13

    Enveloped virus, such as HIV-1, employs membrane fusion mechanism to invade into host cell. HIV-1 gp41 ectodomain uses six-helix bundle configuration to accomplish this process. Using molecular dynamic simulations, we confirmed the stability of this six-helix bundle by showing high occupancy of hydrogen bonds and hydrophobic interactions. Key residues and interactions important for the bundle integration were characterized by force-induced unfolding simulations of six-helix bundle, exhibiting the collapse order of these groups of interactions. Moreover, our results in some way concerted with a previous theory that the formation of coiled-coil choose a route which involved cooperative interactions between the N-terminal and C-terminal helix. -- Highlights: •Unfolding of HIV-1 gp41 six-helix bundle is studied by molecular dynamics simulations. •Specific interactions responsible for the stability of HIV-1 envelope post-fusion conformation were identified. •The gp41 six-helix bundle transition inducing membrane fusion might be a cooperative process of the three subunits.

  2. Integrated HIV care and service engagement among people living with HIV who use drugs in a setting with a community-wide treatment as prevention initiative: a qualitative study in Vancouver, Canada.

    Science.gov (United States)

    Collins, Alexandra B; Parashar, Surita; Hogg, Robert S; Fernando, Saranee; Worthington, Catherine; McDougall, Patrick; Turje, Rosalind Baltzer; McNeil, Ryan

    2017-03-03

    Social-structural inequities impede access to, and retention in, HIV care among structurally vulnerable people living with HIV (PLHIV) who use drugs. The resulting disparities in HIV-related outcomes among PLHIV who use drugs pose barriers to the optimization of HIV treatment as prevention (TasP) initiatives. We undertook this study to examine engagement with, and impacts of, an integrated HIV care services model tailored to the needs of PLHIV who use drugs in Vancouver, Canada - a setting with a community-wide TasP initiative. We conducted qualitative interviews with 30 PLHIV who use drugs recruited from the Dr. Peter Centre, an HIV care facility operating under an integrated services model and harm reduction approach. We employed novel analytical techniques to analyse participants' service trajectories within this facility to understand how this HIV service environment influences access to, and retention in, HIV care among structurally vulnerable PLHIV who use drugs. Our findings demonstrate that participants' structural vulnerability shaped their engagement with the HIV care facility that provided access to resources that facilitated retention in HIV care and antiretroviral treatment adherence. Additionally, the integrated service environment helped reduce burdens associated with living in extreme poverty by meeting participants' subsistence (e.g. food, shelter) needs. Moreover, access to multiple supports created a structured environment in which participants could develop routine service use patterns and have prolonged engagement with supportive care services. Our findings demonstrate that low-barrier service models can mitigate social and structural barriers to HIV care and complement TasP initiatives for PLHIV who use drugs. These findings highlight the critical role of integrated service models in promoting access to health and support services for structurally vulnerable PLHIV. Complementing structural interventions with integrated service models that are

  3. 'It looks like you just want them when things get rough': civil society perspectives on negative trial results and stakeholder engagement in HIV prevention trials.

    Science.gov (United States)

    Koen, Jennifer; Essack, Zaynab; Slack, Catherine; Lindegger, Graham; Newman, Peter A

    2013-12-01

    Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from South African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised. © 2012 John Wiley & Sons Ltd.

  4. Piloting a Savings-Led Microfinance Intervention with Women Engaging in Sex Work in Mongolia: Further Innovation for HIV Risk Reduction.

    Science.gov (United States)

    Tsai, Laura Cordisco; Witte, Susan S; Aira, Toivgoo; Altantsetseg, Batsukh; Riedel, Marion

    2011-12-30

    This paper describes a pilot study testing the feasibility of an innovative savings-led microfinance intervention in increasing the economic empowerment and reducing the sexual risk behavior of women engaging in sex work in Mongolia. Women's economic vulnerability may increase their risk for HIV by compromising their ability to negotiate safer sex with partners and heightening the likelihood they will exchange sex for survival. Microfinance has been considered a potentially powerful structural HIV prevention strategy with women conducting sex work, as diversification of income sources may increase women's capacity to negotiate safer transactional sex. With 50% of all reported female HIV cases in Mongolia detected among women engaging in sex work, direct prevention intervention with women conducting sex work represents an opportunity to prevent a potentially rapid increase in HIV infection in urban Mongolia. The piloted intervention consisted of a matched savings program in which matched savings could be used for business development or vocational education, combined with financial literacy and business development training for women engaging in sex work. Results of the pilot demonstrate participants' increased confidence in their ability to manage finances, greater hope for pursuing vocational goals, moderate knowledge gains regarding financial literacy, and an initial transition from sex work to alternative income generation for five out of nine participants. The pilot findings highlight the potential for such an intervention and the need for a clinical trial testing the efficacy of savings-led microfinance programs in reducing HIV risk for women engaging in sex work in Mongolia.

  5. Realizing the Promise of the Global Plan: Engaging Communities and Promoting the Health and Human Rights of Women Living With HIV.

    Science.gov (United States)

    Matheson, Rebecca; Brion, Sophie; Sharma, Aditi; Dilmitis, Sophie; Schmitz, Kathrin; Kean, Stuart; Filous, Katie; Murenga, Maurine; Scheepers, Esca; Ukoli, Patricia; Mworeko, Lillian; Yuvaraj, Anandi

    2017-05-01

    The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive highlighted the need to put the health and well-being of women and mothers at the center of efforts to prevent vertical transmission. This article will examine a selection of community engagement practices in 3 key areas: (1) as an accountability tool, (2) in service delivery, and (3) as a facilitator of human rights. The lived experiences of women living with HIV as recipients of and participants in services for the prevention of vertical transmission provide both the framework for an exploration of best community engagement practices and suggestions for the way forward.

  6. Vital need to engage the community in HIV control in South Africa

    Directory of Open Access Journals (Sweden)

    Stefan Hanson

    2015-08-01

    Full Text Available According to the latest 2014 UNAIDS report, which was based on the 2012 South African National HIV Prevalence, Incidence & Behavior Survey, there were between 6.3 and 6.4 million HIV infected people in South Africa. Although the number of new infections appears to have declined in the past 5 years, 370,000 new infections were still estimated to occur in 2013. Young, black women were most at risk with a very high incidence of 4.5%. Of the infected, only 2.2 million were on antiretroviral therapy (ART, meaning that the majority living with HIV was not virally suppressed and thus at risk of infecting somebody else. Eight out of 10 South Africans still believed they were at low risk of HIV infection. Condom use was declining and multiple sexual partnerships were increasing. These findings raise questions about whether current control efforts are properly addressing the drivers of the epidemic. Recent behavior change campaigns target intergenerational sex and blame the high transmission rates among girls on ‘sugar daddies’ thus diverting attention away from common risk behaviors in the general population. Reduction of new infections is crucial. Much of the current global HIV debate focuses on treatment as prevention (TasP – an approach hampered by resource problems and the fact that most people are infected by someone who is unaware of his/her HIV status. This raises doubts TasP alone is a sufficient and sustainable solution to prevention. It is not enough to mainly treat those already infected; there is also a need to allocate more resources to address the root causes – ART plus norm and behavior change. We thus propose increased attention to common sexual and social norms and behaviors. New and harmful community norms are one of the major drivers of the ongoing spread of HIV among young women and men in black communities. Addressing sexual risk behaviors and the gender and sexual norms that influence them to scale requires ensuring

  7. HIV and Drug Resistance: Hitting a Moving Target | Center for Cancer Research

    Science.gov (United States)

    Prior research revealed how HIV-1 makes its destructive entry into the target cell by fusing together the cholesterol-rich lipid bilayer of the viral envelope—made with key glycoproteins gp120 and gp41—and the host cell’s plasma membrane. Cell-viral interactions begin with the binding of gp120 to the CD4 receptor molecule on the target cell, followed by gp120 binding to coreceptors. These coreceptors likely reside in structures called lipid rafts—areas in the cell plasma membrane that are rich in cholesterol, saturated fatty acids, and certain proteins that facilitate the entry of viruses into host cells. Finally, sequences in gp41 trigger the fusion of the viral and cellular lipid bilayers. The lipid rafts are then involved in the production of new viral particles.

  8. Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines.

    Science.gov (United States)

    Decroly, E; Wouters, S; Di Bello, C; Lazure, C; Ruysschaert, J M; Seidah, N G

    1996-11-29

    The human immunodeficiency virus HIV envelope glycoprotein gp160 is synthesized as an inactive precursor, which is processed into its fusiogenic form gp120/gp41 by host cell proteinases during its intracellular trafficking. Kexin/subtilisin-related endoproteases have been proposed to be enzyme candidates for this maturation process. In the present study, 1) we examined the ability of partially purified precursor convertases and their isoforms to cleave gp160 in vitro. The data demonstrate that all the convertases tested specifically cleave the HIV envelope glycoprotein into gp120 and gp41. 2) We demonstrated that a 19-amino acid model peptide spanning the gp120/gp41 junction is cleaved by all convertases at the same gp160 site as that recognized in HIV-infected cells. 3) In an effort to evaluate specific convertase inhibitors, we showed that the alpha1-antitrypsin variant, alpha1-PDX, inhibits equally well the ability of the tested convertases to cleave gp160 in vitro. 4) Three lymphocyte cell lines were screened by reverse transcription polymerase chain reaction in an effort to identify which are the convertases expressed in the most common HIV target, the CD4(+) lymphocytes. The data demonstrate that furin, PC5/6, and the newly cloned PC7 are the main transcribed convertases, suggesting that these proteinases are the major gp160-converting enzymes in T4 lymphocytes.

  9. Social Media Engagement and HIV Testing Among Men Who Have Sex With Men in China: A Nationwide Cross-Sectional Survey

    Science.gov (United States)

    Liu, Chuncheng; Durvasula, Maya; Tang, Weiming; Pan, Stephen; Saffer, Adam J; Wei, Chongyi; Tucker, Joseph D

    2017-01-01

    Background Many interventions find that social media engagement with health promotion materials can translate into behavioral changes. However, only a few studies have examined the ways in which specific actions on various social media platforms are correlated with health behaviors. Objective The objective of this study was to examine the association between social media use and HIV testing behaviors among Chinese men who have sex with men (MSM). Methods In July 2016, a Web-based survey was conducted to recruit MSM in 8 Chinese cities through Blued (Blue City Holdings Ltd.), the world’s largest gay mobile phone app. Data on sociodemographic variables, social media use platforms and behaviors, sexual behaviors, and HIV testing histories were collected. HIV testing–related social media use was defined as having ever engaged with HIV testing content on social media, which was further divided into observing (ie, receiving), endorsing (eg, liking and sharing), and contributing (eg, posting or commenting on HIV testing materials). Confirmatory factor analysis (CFA) was conducted to determine the best division of HIV testing–related social media use. Univariate and multivariable logistic regressions were used to examine the association between HIV testing–related social media use and HIV testing behaviors. Results A total of 2105 individuals participated in the survey. Among them, 46.75% (984) were under the age of 24 years, 35.43% (746) had high school education or less, and 47.74% (587) had condomless sex in the last 3 months. More than half of the respondents (58.14%, 1224/2105) reported HIV testing–related social media use. Additionally, HIV testing–related social media use, especially on multifunctional platforms such as WeChat, was found to be associated with recent HIV testing (adjusted odds ratio [aOR] 2.32, 95% CI 1.66-3.24). Contributing on social media was correlated with recent HIV testing (aOR 2.10, 95% CI 1.40-3.16), but neither observing (aOR 0

  10. Social Media Engagement and HIV Testing Among Men Who Have Sex With Men in China: A Nationwide Cross-Sectional Survey.

    Science.gov (United States)

    Cao, Bolin; Liu, Chuncheng; Durvasula, Maya; Tang, Weiming; Pan, Stephen; Saffer, Adam J; Wei, Chongyi; Tucker, Joseph D

    2017-07-19

    Many interventions find that social media engagement with health promotion materials can translate into behavioral changes. However, only a few studies have examined the ways in which specific actions on various social media platforms are correlated with health behaviors. The objective of this study was to examine the association between social media use and HIV testing behaviors among Chinese men who have sex with men (MSM). In July 2016, a Web-based survey was conducted to recruit MSM in 8 Chinese cities through Blued (Blue City Holdings Ltd.), the world's largest gay mobile phone app. Data on sociodemographic variables, social media use platforms and behaviors, sexual behaviors, and HIV testing histories were collected. HIV testing-related social media use was defined as having ever engaged with HIV testing content on social media, which was further divided into observing (ie, receiving), endorsing (eg, liking and sharing), and contributing (eg, posting or commenting on HIV testing materials). Confirmatory factor analysis (CFA) was conducted to determine the best division of HIV testing-related social media use. Univariate and multivariable logistic regressions were used to examine the association between HIV testing-related social media use and HIV testing behaviors. A total of 2105 individuals participated in the survey. Among them, 46.75% (984) were under the age of 24 years, 35.43% (746) had high school education or less, and 47.74% (587) had condomless sex in the last 3 months. More than half of the respondents (58.14%, 1224/2105) reported HIV testing-related social media use. Additionally, HIV testing-related social media use, especially on multifunctional platforms such as WeChat, was found to be associated with recent HIV testing (adjusted odds ratio [aOR] 2.32, 95% CI 1.66-3.24). Contributing on social media was correlated with recent HIV testing (aOR 2.10, 95% CI 1.40-3.16), but neither observing (aOR 0.66, 95% CI 0.38-1.15) nor endorsing (aOR 1.29, 95

  11. Pharmacy Student Attitudes and Willingness to Engage in Care with People Living with HIV/AIDS.

    Science.gov (United States)

    Rickles, Nathaniel M; Furtek, Kari J; Malladi, Ruthvik; Ng, Eric; Zhou, Maria

    2016-04-25

    Objective. To describe the extent to which pharmacy students hold negative attitudes toward people living with HIV/AIDS (PLWHA) and to determine whether background variables, student knowledge, and professional attitudes may affect willingness to care for PLWHA. Methods. An online survey tool was developed and administered to 150 pharmacy students in their third professional year. Descriptive and stepwise multivariate regressions were performed. Results. While descriptive results showed a majority of respondents had favorable professional attitudes towards caring for PLWHA, most pharmacy students expressed discomfort with specific attitudes about being in close physical contact and receiving selected services from PLWHA. Multivariate results revealed that: (1) being a minority predicted greater knowledge; (2) having received prior HIV instruction and greater HIV knowledge predicted more positive professional attitudes caring for PLWHA; (3) being more socially liberal, having more positive professional attitudes caring for PLWHA, and having greater empathy towards PLWHA predicted student willingness to provide services. Conclusion. Future educational interventions specifically targeted toward socially conservative whites may impact greater student willingness to care for PLWHA. Additional research should also explore the generalizability of the present findings and modeling to pharmacy students in other regions of the country.

  12. “Research participants want to feel they are better off than they were before research was introduced to them”: engaging cameroonian rural plantation populations in HIV research

    Directory of Open Access Journals (Sweden)

    Kiawi Emmanuel

    2012-06-01

    Full Text Available Abstract Background During a period of evolving international consensus on how to engage communities in research, facilitators and barriers to participation in HIV prevention research were explored in a rural plantation community in the coastal region of Cameroon. Methods A formative rapid assessment using structured observations, focus group discussions (FGD, and key informant interviews (KIIs was conducted with a purposive non-probabilistic sample of plantation workers and their household members. Eligibility criteria included living or working >1 year within the plantation community and age >18 years. Both rapid and in-depth techniques were used to complete thematic analysis. Results Sixty-five persons participated in the study (6 FGDs and 12 KIIs. Participants viewed malaria and gastrointestinal conditions as more common health concerns than HIV. They identified three factors as contributing to HIV risk: concurrent sexual relationships, sex work, and infrequent condom use. Interviewees perceived that the community would participate in HIV research if it is designed to: (1 improve community welfare, (2 provide comprehensive health services and treatment for illnesses, (3 protect the personal information of participants, especially those who test positive for HIV, (4 provide participant incentives, (5 incorporate community input, and (6 minimize disruptions to “everyday life”. Barriers to participation included: (1 fear of HIV testing, (2 mistrust of researchers given possible disrespect or intolerance of plantation community life and lack of concern for communication, (3 time commitment demands, (3 medical care and treatment that would be difficult or costly to access, and (4 life disruptions along with potential requirements for changes in behaviour (i.e., engage in or abstain from alcohol use and sex activities. Conclusions Consistent with UNAIDS guidelines for good participatory practice in HIV prevention research, study

  13. HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach.

    Directory of Open Access Journals (Sweden)

    Qiana L Matthews

    2010-07-01

    Full Text Available Adenoviral (Ad vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5 immunity. In order to circumvent the need for antigen expression via transgene incorporation, the "antigen capsid-incorporation" strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER, derived from HIV glycoprotein gp41 (gp41. Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response.

  14. Glycosylation in HIV-1 envelope glycoprotein and its biological implications

    KAUST Repository

    Ho, Yung Shwen

    2013-08-01

    Glycosylation of HIV-1 envelope proteins (Env gp120/gp41) plays a vital role in viral evasion from the host immune response, which occurs through the masking of key neutralization epitopes and the presentation of the Env glycosylation as \\'self\\' to the host immune system. Env glycosylation is generally conserved, yet its continual evolution plays an important role in modulating viral infectivity and Env immunogenicity. Thus, it is believed that Env glycosylation, which is a vital part of the HIV-1 architecture, also controls intra- and inter-clade genetic variations. Discerning intra- and inter-clade glycosylation variations could therefore yield important information for understanding the molecular and biological differences between HIV clades and may assist in effectively designing Env-based immunogens and in clearly understanding HIV vaccines. This review provides an in-depth perspective of various aspects of Env glycosylation in the context of HIV-1 pathogenesis. © 2013 Future Medicine Ltd.

  15. Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160.

    Science.gov (United States)

    Decroly, E; Benjannet, S; Savaria, D; Seidah, N G

    1997-03-17

    The intracellular proteolytic processing of HIV envelope glycoprotein gp160 into gp120/gp41 is an essential step for virus infectivity. Several convertases, belonging to the pro-protein convertase family, have been proposed as candidate gp160 processing enzymes. Here we demonstrate using RT-PCR that resting human T4 lymphocytes weakly express PC7, furin, and PC5 mRNA whereas lymphocytes activated under conditions favoring HIV replication express 5-10-fold higher levels of furin and PC7. In this report, we examined the capability of the newly cloned convertase PC7 to cleave gp160 into gp120/gp41 and compared it to furin. This was carried out in a cell-based assay whereby both gp160 and the cognate convertase were co-expressed in the constitutively secreting BSC40 cells and in the regulated AtT20 cells, as well as using two in vitro assays which examined the cleavage of gp160 or of a synthetic peptide spanning the cleavage site. The data demonstrate that PC7 can cleave specifically and in a cell-type specific manner gp160 into gp120gp41, suggesting that both furin and PC7 are so far the major PC-like candidate gp160 convertase in T4 lymphocytes.

  16. Chimeric Cyanovirin-MPER Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1

    OpenAIRE

    Contarino, Mark; Bastian, Arangassery R.; Kalyana Sundaram, Ramalingam Venkat; McFadden, Karyn; Duffy, Caitlin; Gangupomu, Vamshi; Baker, Michelle; Abrams, Cameron; Chaiken, Irwin

    2013-01-01

    Human immunodeficiency virus (HIV) is the primary etiologic agent responsible for the AIDS pandemic. In this work, we used a chimeric recombinant protein strategy to test the possibility of irreversibly destroying the HIV-1 virion using an agent that simultaneously binds the Env protein and viral membrane. We constructed a fusion of the lectin cyanovirin-N (CVN) and the gp41 membrane-proximal external region (MPER) peptide with a variable-length (Gly4Ser)x linker (where x is 4 or 8) between t...

  17. Bifunctional recombinant fusion proteins for rapid detection of antibodies to both HIV-1 and HIV-2 in whole blood

    Directory of Open Access Journals (Sweden)

    Chaudhary Vijay K

    2006-09-01

    Full Text Available Abstract Background Availability of accurate diagnostic tests has been helpful in curtailing the spread of HIV infection. Among these, simple, point of care, inexpensive tests which require only a drop of blood from finger-prick and give reliable results within minutes are a must for expansion of testing services and for reaching mobile and marginalised populations. Such tests will not only be a boon for the infrastructure-starved developing and underdeveloped countries but will also be extremely useful in developed countries where post-testing compliance is a major problem. Our laboratory has been involved in developing reagents for heamagglutination-based rapid detection of antibodies to HIV in whole blood using recombinant molecules specific for either HIV-1 or HIV-2. Since it is not required of a screening test to differentially detect HIV and HIV-2, it would useful to create a single molecule capable of simultaneous detection of both HIV-1 and HIV-2 in a drop of blood. Results The present paper describes designing, high-level expression and large-scale purification of new molecules comprising recombinant anti-RBC Fab fused to immunodominant regions of envelope sequences from both gp41 of HIV-1 and gp36 of HIV-2. These immunodominant regions of HIV envelope contain cysteine residues, which make disulfide bond and can interfere with the assembly of light chain and heavy chain fragment to make Fab molecule in vitro. To circumvent this problem, a series of fusion proteins having different combinations of native and mutant envelope sequences were constructed, purified and evaluated for their efficacy in detecting antibodies to HIV-1 and HIV-2. A chimeric molecule comprising native envelope sequence of gp41 of HIV-1 and modified envelope sequence of gp36 of HIV-2 gave good production yield and also detected both HIV-1 and HIV-2 samples with high sensitivity and specificity. Conclusion The new bifunctional antibody fusion protein identified in

  18. Formative Work and Community Engagement Approaches for Implementing an HIV Intervention in Botswana Schools.

    Science.gov (United States)

    Miller, Kim S; Cham, Haddi J; Taylor, Eboni M; Berrier, Faith L; Duffy, Meghan; Vig, Jessica; Chipazi, Lily; Chakalisa, Chawada; Sidibe, Sekou; Swart, Kenau; Tau, Nontobeko Sylvia; Clark, Leslie F

    2016-08-01

    Providing adolescents with evidence-based sexual risk reduction interventions is critical to addressing the HIV/AIDS epidemic among adolescents in sub-Saharan Africa. Project AIM (Adult Identity Mentoring) is an innovative, evidence-based, youth development intervention that is being evaluated for the first time in Botswana through a 3-year (2015-2017), 50-school cluster randomized controlled trial, including testing for herpes simplex virus type 2 as a sexual activity biomarker. Conducting a trial of this magnitude requires the support and collaboration of government and community stakeholders. All school staff, including teachers, must be well informed about the study; dedicated staff placed at each school can help to improve school and community familiarity with the study, improve the information flow, and relieve some of the burden study activities places on schools.

  19. Critical race theory as a tool for understanding poor engagement along the HIV care continuum among African American/Black and Hispanic persons living with HIV in the United States: a qualitative exploration.

    Science.gov (United States)

    Freeman, Robert; Gwadz, Marya Viorst; Silverman, Elizabeth; Kutnick, Alexandra; Leonard, Noelle R; Ritchie, Amanda S; Reed, Jennifer; Martinez, Belkis Y

    2017-03-24

    African American/Black and Hispanic persons living with HIV (AABH-PLWH) in the U.S. evidence insufficient engagement in HIV care and low uptake of HIV antiretroviral therapy, leading to suboptimal clinical outcomes. The present qualitative study used critical race theory, and incorporated intersectionality theory, to understand AABH-PLWH's perspectives on the mechanisms by which structural racism; that is, the macro-level systems that reinforce inequities among racial/ethnic groups, influence health decisions and behaviors. Participants were adult AABH-PLWH in New York City who were not taking antiretroviral therapy nor well engaged in HIV care (N = 37). Participants were purposively sampled for maximum variation from a larger study, and engaged in semi-structured in-depth interviews that were audio-recorded and professionally transcribed verbatim. Data were analyzed using a systematic content analysis approach. We found AABH-PLWH experienced HIV care and medication decisions through a historical and cultural lens incorporating knowledge of past and present structural racism. This contextual knowledge included awareness of past maltreatment of people of color in medical research. Further, these understandings were linked to the history of HIV antiretroviral therapy itself, including awareness of the first HIV antiretroviral regimen; namely, AZT (zidovudine) mono-therapy, which was initially prescribed in unacceptably high doses, causing serious side effects, but with only modest efficacy. In this historical/cultural context, aspects of structural racism negatively influenced health care decisions and behavior in four main ways: 1) via the extent to which healthcare settings were experienced as overly institutionalized and, therefore, dehumanizing; 2) distrust of medical institutions and healthcare providers, which led AABH-PLWH to feel pressured to take HIV antiretroviral therapy when it was offered; 3) perceptions that patients are excluded from the health

  20. Contribution of intrinsic reactivity of the HIV-1 envelope glycoproteins to CD4-independent infection and global inhibitor sensitivity.

    Directory of Open Access Journals (Sweden)

    Hillel Haim

    2011-06-01

    Full Text Available Human immunodeficiency virus (HIV-1 enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the "intrinsic reactivity" of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant ("Tier 2-like" viruses, globally sensitive ("Tier 1" viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of

  1. Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity

    Science.gov (United States)

    Haim, Hillel; Strack, Bettina; Kassa, Aemro; Madani, Navid; Wang, Liping; Courter, Joel R.; Princiotto, Amy; McGee, Kathleen; Pacheco, Beatriz; Seaman, Michael S.; Smith, Amos B.; Sodroski, Joseph

    2011-01-01

    Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the “intrinsic reactivity” of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant (“Tier 2-like”) viruses, globally sensitive (“Tier 1”) viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of

  2. Understanding HIV care delays in the US South and the role of the social-level in HIV care engagement/retention: a qualitative study

    National Research Council Canada - National Science Library

    Sprague, Courtenay; Simon, Sara E

    2014-01-01

    In a significant geographical shift in the distribution of HIV infection, the US South--comprising 17 states--now has the greatest number of adults and adolescents with HIV (PLHIV) in the nation. More than 60...

  3. Engagement with Health Care Providers Affects Self- Efficacy, Self-Esteem, Medication Adherence and Quality of Life in People Living with HIV

    Science.gov (United States)

    Chen, Wei-Ti; Wantland, Dean; Reid, Paula; Corless, Inge B; Eller, Lucille S.; Iipinge, Scholastika; Holzemer, William L; Nokes, Kathleen; Sefcik, Elizbeth; Rivero-Mendez, Marta; Voss, Joachim; Nicholas, Patrice; Phillips, J. Craig; Brion, John M.; Rose, Caro Dawson; Portillo, Carmen J; Kirksey, Kenn; Sullivan, Kathleen M; Johnson, Mallory O; Tyer-Viola, Lynda; Webel, Allison R

    2014-01-01

    The engagement of patients with their health care providers (HCP) improves patients’ quality of life (QOL), adherence to antiretroviral therapy, and life satisfaction. Engagement with HCP includes access to HCP as needed, information sharing, involvement of client in decision making and self-care activities, respect and support of the HCP for the client’s choices, and management of client concerns. This study compares country-level differences in patients’ engagement with HCP and assesses statistical associations relative to adherence rates, self-efficacy, self-esteem, QOL, and symptom self-reporting by people living with HIV (PLHIV). A convenience sample of 2,182 PLHIV was enrolled in the United States, Canada, Puerto Rico, Namibia, and China. Cross-sectional data were collected between September 2009 and January 2011. Inclusion criteria were being at least 18 years of age, diagnosed with HIV, able to provide informed consent, and able to communicate in the local language with site researchers. In the HCP scale, a low score indicated greater provider engagement. Country comparisons showed that PLHIV in Namibia had the most HCP engagement (OR 2.80, p < 0.001) and that PLHIV in China had the least engagement (OR −7.03, p < 0.0001) compared to the PLHIV in the Western countries. Individuals having better HCP engagement showed better self-efficacy for adherence (t = −5.22, p < 0.0001), missed fewer medication doses (t = 1.92, p ≤ 0.05), had lower self-esteem ratings (t = 2.67, p < 0.01), fewer self-reported symptoms (t = 3.25, p < 0.0001), and better overall QOL physical condition (t = −3.39, p < 0.001). This study suggests that promoting engagement with the HCP is necessary to facilitate skills that help PLHIV manage their HIV. To improve ART adherence, HCPs should work on strategies to enhance self-efficacy and self-esteem, therefore, exhibiting fewer HIV-related symptoms and missing less medication doses to achieve better QOL. PMID:24575329

  4. Efficacy of a savings-led microfinance intervention to reduce sexual risk for HIV among women engaged in sex work: a randomized clinical trial.

    Science.gov (United States)

    Witte, Susan S; Aira, Toivgoo; Tsai, Laura Cordisco; Riedel, Marion; Offringa, Reid; Chang, Mingway; El-Bassel, Nabila; Ssewamala, Fred

    2015-03-01

    We tested whether a structural intervention combining savings-led microfinance and HIV prevention components would achieve enhanced reductions in sexual risk among women engaging in street-based sex work in Ulaanbaatar, Mongolia, compared with an HIV prevention intervention alone. Between November 2011 and August 2012, we randomized 107 eligible women who completed baseline assessments to either a 4-session HIV sexual risk reduction intervention (HIVSRR) alone (n=50) or a 34-session HIVSRR plus a savings-led microfinance intervention (n=57). At 3- and 6-month follow-up assessments, participants reported unprotected acts of vaginal intercourse with paying partners and number of paying partners with whom they engaged in sexual intercourse in the previous 90 days. Using Poisson and zero-inflated Poisson model regressions, we examined the effects of assignment to treatment versus control condition on outcomes. At 6-month follow-up, the HIVSRR plus microfinance participants reported significantly fewer paying sexual partners and were more likely to report zero unprotected vaginal sex acts with paying sexual partners. Findings advance the HIV prevention repertoire for women, demonstrating that risk reduction may be achieved through a structural intervention that relies on asset building, including savings, and alternatives to income from sex work.

  5. TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+ T cells across the virological synapse

    Directory of Open Access Journals (Sweden)

    Blanchet Fabien P

    2013-01-01

    Full Text Available Abstract Background Dendritic cells and their subsets, located at mucosal surfaces, are among the first immune cells to encounter disseminating pathogens. The cellular restriction factor BST-2/tetherin (also known as CD317 or HM1.24 potently restricts HIV-1 release by retaining viral particles at the cell surface in many cell types, including primary cells such as macrophages. However, BST-2/tetherin does not efficiently restrict HIV-1 infection in immature dendritic cells. Results We now report that BST-2/tetherin expression in myeloid (myDC and monocyte-derived dendritic cells (DC can be significantly up-regulated by IFN-α treatment and TLR-4 engagement with LPS. In contrast to HeLa or 293T cells, infectious HIV-1 release in immature DC and IFN-α–matured DC was only modestly affected in the absence of Vpu compared to wild-type viruses. Strikingly, immunofluorescence analysis revealed that BST-2/tetherin was excluded from HIV containing tetraspanin-enriched microdomains (TEMs in both immature DC and IFN-α–matured DC. In contrast, in LPS-mediated mature DC, BST-2/tetherin exerted a significant restriction in transfer of HIV-1 infection to CD4+ T cells. Additionally, LPS, but not IFN-α stimulation of immature DC, leads to a dramatic redistribution of cellular restriction factors to the TEM as well as at the virological synapse between DC and CD4+ T cells. Conclusions In conclusion, we demonstrate that TLR-4 engagement in immature DC significantly up-regulates the intrinsic antiviral activity of BST-2/tetherin, during cis-infection of CD4+ T cells across the DC/T cell virological synapse. Manipulating the function and potency of cellular restriction factors such as BST-2/tetherin to HIV-1 infection, has implications in the design of antiviral therapeutic strategies.

  6. What’s God got to do with it? Engaging African American faith-based institutions in HIV prevention

    OpenAIRE

    Nunn, Amy; Cornwall, Alexandra; Thomas, Gladys; Waller, Pastor Alyn; Friend, Rafiyq; Broadnax, Pastor Jay; Flanigan, Timothy

    2013-01-01

    African Americans are disproportionately infected and affected by HIV/AIDS. Although faith-based institutions play critical leadership roles in the African American community, the faith-based response to HIV/AIDS has historically been lacking. We explore recent successful strategies of a citywide HIV/AIDS awareness and testing campaign developed in partnership with 40 African American faith-based institutions in Philadelphia, Pennsylvania, a city with some of the United State’s highest HIV in...

  7. A nonparametric procedure for defining a new humoral immunologic profile in a pilot study on HIV infected patients.

    Directory of Open Access Journals (Sweden)

    Chiara Brombin

    Full Text Available This work aims at identifying a set of humoral immunologic parameters that improve prediction of the activation process in HIV patients. Starting from the well-known impact of humoral immunity in HIV infection, there is still a lack of knowledge in defining the role of the modulation of functional activity and titers of serum antibodies from early stage of infection to the development of AIDS. We propose an integrated approach that combines humoral and clinical parameters in defining the host immunity, implementing algorithms associated with virus control. A number of humoral parameters were simultaneously evaluated in a whole range of serum samples from HIV-positive patients. This issue has been afforded accounting for estimation problems typically related to "feasibility" studies where small sample size in each group and large number of parameters are jointly estimated. We used nonparametric statistical procedures to identify biomarkers in our study which included 42 subjects stratified on five different stages of HIV infection, i.e., Elite Controllers (EC, Long Term Non Progressors (LTNP, HAART, AIDS and Acute Infection (AI. The main goal of the paper is to illustrate a novel profiling method for helping to design a further confirmatory study. A set of seventeen different HIV-specific blood humoral factors were analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope of the HR1 region and to CCR5; neutralization activity against five different virus strains and ADCC were also evaluated. Patients were selected on the basis of CD4 cell counts, HIV/RNA and clinical status. The Classification and Regression Trees (CART approach has been used to uncover specific patterns of humoral parameters in different stages of HIV disease. Virus neutralization of primary virus strains and antibodies to gp41 were required to classify patients, suggesting

  8. A nonparametric procedure for defining a new humoral immunologic profile in a pilot study on HIV infected patients.

    Science.gov (United States)

    Brombin, Chiara; Diomede, Lorenzo; Tudor, Daniela; Drillet, Anne Sophie; Pastori, Claudia; Poli, Elena; Riva, Agostino; Uberti-Foppa, Caterina; Galli, Massimo; Di Serio, Clelia; Bomsel, Morgane; Lopalco, Lucia

    2013-01-01

    This work aims at identifying a set of humoral immunologic parameters that improve prediction of the activation process in HIV patients. Starting from the well-known impact of humoral immunity in HIV infection, there is still a lack of knowledge in defining the role of the modulation of functional activity and titers of serum antibodies from early stage of infection to the development of AIDS. We propose an integrated approach that combines humoral and clinical parameters in defining the host immunity, implementing algorithms associated with virus control. A number of humoral parameters were simultaneously evaluated in a whole range of serum samples from HIV-positive patients. This issue has been afforded accounting for estimation problems typically related to "feasibility" studies where small sample size in each group and large number of parameters are jointly estimated. We used nonparametric statistical procedures to identify biomarkers in our study which included 42 subjects stratified on five different stages of HIV infection, i.e., Elite Controllers (EC), Long Term Non Progressors (LTNP), HAART, AIDS and Acute Infection (AI). The main goal of the paper is to illustrate a novel profiling method for helping to design a further confirmatory study. A set of seventeen different HIV-specific blood humoral factors were analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope of the HR1 region and to CCR5; neutralization activity against five different virus strains and ADCC were also evaluated. Patients were selected on the basis of CD4 cell counts, HIV/RNA and clinical status. The Classification and Regression Trees (CART) approach has been used to uncover specific patterns of humoral parameters in different stages of HIV disease. Virus neutralization of primary virus strains and antibodies to gp41 were required to classify patients, suggesting that clinical

  9. Innovative strategies using communications technologies to engage gay men and other men who have sex with men into early HIV testing and treatment in Thailand.

    Science.gov (United States)

    Anand, Tarandeep; Nitpolprasert, Chattiya; Ananworanich, Jintanat; Pakam, Charnwit; Nonenoy, Siriporn; Jantarapakde, Jureeporn; Sohn, Annette H; Phanuphak, Praphan; Phanuphak, Nittaya

    2015-04-01

    One-in-three men who have sex with men (MSM) surveyed between 2007 and 2010 in Bangkok were HIV infected; 54% of new infections in Thailand are expected to be among MSM. Although MSM are the top internet-accessing population in Thailand, it has not been optimally used to scale up early HIV testing and counselling (HTC) and linkage to treatment. Thailand needs innovative technology-based strategies to help address the exploding epidemic of HIV among gay men and other MSM. Adam's Love, an innovative web-based communications strategy, was launched in 2011 by the Thai Red Cross AIDS Research Centre. It includes a dedicated website, integrated social media and web message boards for online counselling, recruitment and appointment making, a club membership programme offering non-financial incentives for HTC, targeted marketing and promotions, and collaboration with MSM-friendly clinics and private hospitals to improve accessibility of HTC services. Between September 2011 and January 2015, the website engaged 1.69 million viewers, and gained more than 8 million page views. An estimated 11,120 gay men and other MSM received online counselling; 8,288 MSM were referred to HTC services; 1,223 to STI testing services; and 1,112 MSM living with HIV were advised regarding HIV treatment. In total, 1,181 MSM recruited online were enrolled in the club membership programme, and 15.5% were diagnosed with HIV. The Adam's Love programme has successfully demonstrated the potential for utilising 'online-to-offline' recruitment models in Thailand, and has attracted national and regional recognition as a trusted resource on HIV and referral to testing and care.

  10. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies

    Science.gov (United States)

    Yang, Guang; Holl, T. Matt; Liu, Yang; Li, Yi; Lu, Xiaozhi; Nicely, Nathan I.; Kepler, Thomas B.; Alam, S. Munir; Liao, Hua-Xin; Cain, Derek W.; Spicer, Leonard; VandeBerg, John L.; Haynes, Barton F.

    2013-01-01

    Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 gp41 in man may be proscribed by immune tolerance because mice expressing the VH and VL regions of 2F5 have a block in B cell development that is characteristic of central tolerance. This developmental blockade implies the presence of tolerizing autoantigens that are mimicked by the membrane-proximal external region of HIV-1 gp41. We identify human kynureninase (KYNU) and splicing factor 3b subunit 3 (SF3B3) as the primary conserved, vertebrate self-antigens recognized by the 2F5 and 4E10 antibodies, respectively. 2F5 binds the H4 domain of KYNU which contains the complete 2F5 linear epitope (ELDKWA). 4E10 recognizes an epitope of SF3B3 that is strongly dependent on hydrophobic interactions. Opossums carry a rare KYNU H4 domain that abolishes 2F5 binding, but they retain the SF3B3 4E10 epitope. Immunization of opossums with HIV-1 gp140 induced extraordinary titers of serum antibody to the 2F5 ELDKWA epitope but little or nothing to the 4E10 determinant. Identification of structural motifs shared by vertebrates and HIV-1 provides direct evidence that immunological tolerance can impair humoral responses to HIV-1. PMID:23359068

  11. Evaluation of the Tsima community mobilization intervention to improve engagement in HIV testing and care in South Africa: study protocol for a cluster randomized trial.

    Science.gov (United States)

    Lippman, Sheri A; Pettifor, Audrey; Rebombo, Dumisani; Julien, Aimée; Wagner, Ryan G; Kang Dufour, Mi-Suk; Kabudula, Chodziwadziwa Whiteson; Neilands, Torsten B; Twine, Rhian; Gottert, Ann; Gómez-Olivé, F Xavier; Tollman, Stephen M; Sanne, Ian; Peacock, Dean; Kahn, Kathleen

    2017-01-17

    HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care-including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care. Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18-49-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level

  12. A Community-Engaged Approach to Developing an mHealth HIV/STI and Drug Abuse Preventive Intervention for Primary Care: A Qualitative Study.

    Science.gov (United States)

    Cordova, David; Bauermeister, Jose A; Fessler, Kathryn; Delva, Jorge; Nelson, Annabelle; Nurenberg, Rachel; Mendoza Lua, Frania; Alers-Rojas, Francheska; Salas-Wright, Christopher P

    2015-12-18

    Despite ongoing prevention efforts, HIV and other sexually transmitted infections (HIV/STIs) and drug use remain public health concerns. Urban adolescents, many of whom are underserved and racial minorities, are disproportionately affected. Recent changes in policy, including the Affordable Care Act, and advances in technology provide HIV/STI and drug abuse prevention scientists with unique opportunities to deliver mobile health (mHealth) preventive interventions in primary care. The purpose of this community-engaged study was to develop an mHealth version of the Storytelling for Empowerment preventive intervention for primary care (hereinafter referred to as "S4E"). A total of 29 adolescents were recruited from a youth-centered primary care clinic in Southeast, Michigan, to participate in qualitative interviews. Participants were predominantly African American (n=19, 65.5%) and female (n=21, 72.4%) with a mean age of 16.23 (SD 2.09). The principles of community-based participatory research (CBPR), in conjunction with agile software development and the recommended core prevention principles of the National Institute on Drug Abuse (NIDA) were employed during S4E development. CBPR principles are aimed at improving the effectiveness of research by addressing locally relevant health problems, working with community strengths, and translating basic science into applied research. Complementing this approach, the NIDA prevention principles are derived from decades of drug abuse prevention research aimed at increasing the effectiveness and uptake of programs, through the development of culturally specific interventions and ensuring the structure, content, and delivery of the intervention fit the needs of the community. Data were analyzed using thematic analysis. A total of 5 themes emerged from the data: (1) acceptability of the mHealth app to adolescents in primary care, (2) inclusion of a risk assessment to improve clinician-adolescent HIV/STI and drug use communication

  13. HIV subtype D is associated with dementia, compared with subtype A, in immunosuppressed individuals at risk of cognitive impairment in Kampala, Uganda.

    Science.gov (United States)

    Sacktor, Ned; Nakasujja, Noeline; Skolasky, Richard L; Rezapour, Mona; Robertson, Kevin; Musisi, Seggane; Katabira, Elly; Ronald, Allan; Clifford, David B; Laeyendecker, Oliver; Quinn, Thomas C

    2009-09-01

    In the United States, clade B is the predominant human immunodeficiency virus (HIV) subtype, whereas in sub-Saharan Africa, clades A, C, and D are the predominant subtypes. HIV subtype may have an impact on HIV disease progression. The effect of HIV subtype on the risk of dementia has, to our knowledge, not been examined. The objective of this study was to examine the relationship between HIV subtype and the severity of HIV-associated cognitive impairment among individuals initiating antiretroviral therapy in Uganda. Sixty antiretroviral-naive HIV-infected individuals with advanced immunosuppression who were at risk of HIV-associated cognitive impairment underwent neurological, neuropsychological, and functional assessments, and gag and gp41 regions were subtyped. Subtype assignments were generated by sequence analysis using a portion of the gag and gp41 regions. Thirty-three HIV-infected individuals were infected with subtype A, 2 with subtype C, 9 with subtype D, and 16 with A/D recombinants. Eight (89%) of 9 HIV-infected individuals with subtype D had dementia, compared with 7 (24%) of 33 HIV-infected individuals with subtype A (P = .004). These results suggest that, in untreated HIV-infected individuals with advanced immunosuppression who are at risk of developing HIV-associated cognitive impairment, HIV dementia may be more common among patients infected with subtype D virus than among those infected with subtype A virus. These findings provide the first evidence, to our knowledge, to demonstrate that HIV subtypes may have a pathogenetic factor with respect to their capacity to cause cognitive impairment. Additional studies are needed to confirm this observation and to define the mechanism by which subtype D leads to an increased risk of neuropathogenesis.

  14. HIV, breast cancer and vaccines: what do high-profile cases reveal about stakeholder engagement in research?

    Science.gov (United States)

    Morain, Stephanie R; Concannon, Thomas W; Wittenberg, Eve

    2017-01-01

    Substantially engaging stakeholders in research involves making extensive changes to the full life cycle of research, from the initial stage of selecting research priorities to the final stages of dissemination and implementation. Recent scholarship has explored logistical and methodological challenges, including the time, training and resources required for engagement. However, inadequate attention has been given to the intended ends or goals of engagement - what do we want engagement to achieve? An examination of historical case studies can yield important insights regarding engagement and its intended ends. Using historical perspective methods, we explore how clarity about the ends of engagement can inform the design of engagement efforts and lead to better outcomes. We present several lessons for improving stakeholder-engaged research.

  15. Enhancing efficacy and mucosa-tropic distribution of an oral HIV-PsV DNA vaccine in animal models.

    Science.gov (United States)

    Fu, Jie; Bian, Guangxing; Zhao, Bijun; Dong, Zengxiang; Sun, Xiao; Chen, Fang; Ou, Lun; Song, Haifeng

    2009-12-01

    A strategy combined the oral delivery route and bovine papillomavirus (BPV) pseudovirus (PsV)-based human immunodeficiency virus (HIV) DNA vaccine, which has been proven to enhance the mucosal immunization compared with the systemic immunization and in general does not induce effective mucosal immune responses. In this study, the immune responses against the BPV expressing HIV gp41 epitopes (ELDKWA, NWFDIT) after oral administration in Cynomolgus monkeys (Macaca fascicularis) were assessed, and the biodistribution of plasmid DNA encapsulated in the papillomavirus-like particles (VLPs) were evaluated in murine models. Results showed that oral immunization with the HIV-PsV DNA vaccine in monkey generated p24 and gp41 epitopes-specific serum IgG. Importantly, these induced antibodies had been shown to neutralize HIV-1 primary strain. In addition, the advantage of VLPs as vehicles delivering genes had been first revealed in biodistribution results. Therefore, orally administered HIV-PsV DNA vaccine was well-tolerated, enhanced the mucosa targeting property of the plasmid DNA, and reduced the nontargeting distribution, which indicate that it would reduce stress associated with systemic vaccination.

  16. HIV

    African Journals Online (AJOL)

    Introduction. The·human immunodeficiency virus (HIV) can be transmiHed from one person to onother through the use of non-sterile nee- dles, syringes, and other skin-piercing and invasive instruments. Proper .sterilization of all such instruments is therefore important to prevent its transmission. HIV is very sensitive to ...

  17. hiv

    African Journals Online (AJOL)

    2016-03-31

    Mar 31, 2016 ... Indexed By: African Journal Online (AJOL); Texila American University; Genamics; Scholarsteer; EIJASR; CAS-American Chemical. Society; and IRMS Informatics India (J-Gate). ABSTRACT. This study evaluated the effect of HIV infection on CD4 T-lymphocyte depletion in people living with HIV/AIDS.

  18. HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda.

    Science.gov (United States)

    Sacktor, Ned; Nakasujja, Noeline; Redd, Andrew D; Manucci, Jordyn; Laeyendecker, Oliver; Wendel, Sarah K; Porcella, Stephen F; Martens, Craig; Bruno, Daniel; Skolasky, Richard L; Okonkwo, Ozioma C; Robertson, Kevin; Musisi, Seggane; Katabira, Elly; Quinn, Thomas C

    2014-06-01

    HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/μL and Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count = 233 cells/μL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results.

  19. HIV-1 subtype C envelope characteristics associated with divergent rates of chronic disease progression

    Directory of Open Access Journals (Sweden)

    Goulder Philip JR

    2010-11-01

    Full Text Available Abstract Background HIV-1 envelope diversity remains a significant challenge for the development of an efficacious vaccine. The evolutionary forces that shape the diversity of envelope are incompletely understood. HIV-1 subtype C envelope in particular shows significant differences and unique characteristics compared to its subtype B counterpart. Here we applied the single genome sequencing strategy of plasma derived virus from a cohort of therapy naïve chronically infected individuals in order to study diversity, divergence patterns and envelope characteristics across the entire HIV-1 subtype C gp160 in 4 slow progressors and 4 progressors over an average of 19.5 months. Results Sequence analysis indicated that intra-patient nucleotide diversity within the entire envelope was higher in slow progressors, but did not reach statistical significance (p = 0.07. However, intra-patient nucleotide diversity was significantly higher in slow progressors compared to progressors in the C2 (p = 0.0006, V3 (p = 0.01 and C3 (p = 0.005 regions. Increased amino acid length and fewer potential N-linked glycosylation sites (PNGs were observed in the V1-V4 in slow progressors compared to progressors (p = 0.009 and p = 0.02 respectively. Similarly, gp41 in the progressors was significantly longer and had fewer PNGs compared to slow progressors (p = 0.02 and p = 0.02 respectively. Positive selection hotspots mapped mainly to V1, C3, V4, C4 and gp41 in slow progressors, whereas hotspots mapped mainly to gp41 in progressors. Signature consensus sequence differences between the groups occurred mainly in gp41. Conclusions These data suggest that separate regions of envelope are under differential selective forces, and that envelope evolution differs based on disease course. Differences between slow progressors and progressors may reflect differences in immunological pressure and immune evasion mechanisms. These data also indicate that the pattern of envelope evolution

  20. Is Involvement in Sex Work Associated with Engagement in HIV-Related Medical Care in Latin American Men Who Have Sex with Men? Results of a Large, Multinational Internet Survey.

    Science.gov (United States)

    Biello, Katie B; Oldenburg, Catherine E; Rosenberger, Joshua; Mayer, Kenneth H; Novak, David; Mimiaga, Matthew J

    2016-06-01

    Men who have sex with men (MSM) who engage in transactional sex are at increased HIV risk, and face complex barriers to care seeking. Among 2,035 men recruited through an MSM social/sexual networking website in Latin America and who reported being HIV-infected, 186 (9.1%) reported being paid for sex with another man in the past year. Engagement in transactional sex was associated with decreased odds of receiving medical care for HIV (AOR=0.57, 95% CI=0.37-0.85). No significant differences were seen in being on antiretroviral therapy (ART) or ART adherence once in care. Interventions in this population should focus on reducing barriers to engagement in care.

  1. The Short Isoform of BRD4 Promotes HIV-1 Latency by Engaging Repressive SWI/SNF Chromatin-Remodeling Complexes.

    Science.gov (United States)

    Conrad, Ryan J; Fozouni, Parinaz; Thomas, Sean; Sy, Hendrik; Zhang, Qiang; Zhou, Ming-Ming; Ott, Melanie

    2017-09-21

    BET proteins commonly activate cellular gene expression, yet inhibiting their recruitment paradoxically reactivates latent HIV-1 transcription. Here we identify the short isoform of BET family member BRD4 (BRD4S) as a corepressor of HIV-1 transcription. We found that BRD4S was enriched in chromatin fractions of latently infected T cells, and it was more rapidly displaced from chromatin upon BET inhibition than the long isoform. BET inhibition induced marked nucleosome remodeling at the latent HIV-1 promoter, which was dependent on the activity of BRG1-associated factors (BAF), an SWI/SNF chromatin-remodeling complex with known repressive functions in HIV-1 transcription. BRD4S directly bound BRG1, a catalytic subunit of BAF, via its bromodomain and extraterminal (ET) domain, and this isoform was necessary for BRG1 recruitment to latent HIV-1 chromatin. Using chromatin immunoprecipitation sequencing (ChIP-seq) combined with assay for transposase-accessible chromatin coupled to high-throughput sequencing (ATAC-seq) data, we found that the latent HIV-1 promoter phenotypically resembles endogenous long terminal repeat (LTR) sequences, pointing to a select role of BRD4S-BRG1 complexes in genomic silencing of invasive retroelements. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A compensatory mutation provides resistance to disparate HIV fusion inhibitor peptides and enhances membrane fusion.

    Directory of Open Access Journals (Sweden)

    Matthew P Wood

    Full Text Available Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations.

  3. Community perspectives on parental influence on engagement in multiple concurrent sexual partnerships among youth in Tanzania: implications for HIV prevention programming.

    Science.gov (United States)

    Fehringer, Jessica A; Babalola, Stella; Kennedy, Caitlin E; Kajula, Lusajo J; Mbwambo, Jessie K; Kerrigan, Deanna

    2013-01-01

    Although concurrent sexual partnerships (CPs) have been hypothesized to be an important risk factor for HIV in sub-Saharan Africa, the social and cultural factors that encourage CPs are not well understood. This study explored the community's perspectives on the role that parents can play in influencing their children's decision to engage in CPs. We conducted 16 in-depth interviews, 32 focus group discussions, and 16 key informant interviews with 280 adult participants in Tanzania. Data were coded; findings and conclusions were developed based on themes that emerged from coding. Three parental influences on CPs emerged: parent-child communication about sex, both silent and explicit encouragement of CPs, and parental behavior modeling. Parents are typically either too busy or too "embarrassed" to talk with their children about sex and CPs. The information parents do give is often confusing, fear-based, inadequate, and/or only focused on daughters. Parents themselves also encourage CPs through complicity of silence when their daughters come home with extra cash or consumer goods. In some cases, parents overtly encourage their children, particularly daughters, to practice CPs due to the promise of money from wealthy partners. Finally, when parents engage in CPs, the children themselves learn to behave similarly. These results suggest that parents can influence their children's decision to engage in CPs. HIV prevention interventions should address this by promoting parent-child communication about sexuality; associated disease risks and gender-equitable relationships; promoting positive parental role modeling; and educating parents on the implications of encouragement of CPs in their children.

  4. Qualitative insights into implementation, processes, and outcomes of a randomized trial on peer support and HIV care engagement in Rakai, Uganda.

    Science.gov (United States)

    Monroe, April; Nakigozi, Gertrude; Ddaaki, William; Bazaale, Jeremiah Mulamba; Gray, Ronald H; Wawer, Maria J; Reynolds, Steven J; Kennedy, Caitlin E; Chang, Larry W

    2017-01-10

    People living with human immunodeficiency virus (HIV) who have not yet initiated antiretroviral therapy (ART) can benefit from being engaged in care and utilizing preventive interventions. Community-based peer support may be an effective approach to promote these important HIV services. After conducting a randomized trial of the impact of peer support on pre-ART outcomes, we conducted a qualitative evaluation to better understand trial implementation, processes, and results. Overall, 75 participants, including trial participants (clients), peer supporters, and clinic staff, participated in 41 in-depth interviews and 6 focus group discussions. A situated Information Motivation, and Behavioral skills model of behavior change was used to develop semi-structured interview and focus group guides. Transcripts were coded and thematically synthesized. We found that participant narratives were generally consistent with the theoretical model, indicating that peer support improved information, motivation, and behavioral skills, leading to increased engagement in pre-ART care. Clients described how peer supporters reinforced health messages and helped them better understand complicated health information. Peer supporters also helped clients navigate the health system, develop support networks, and identify strategies for remembering medication and clinic appointments. Some peer supporters adopted roles beyond visiting patients, serving as a bridge between the client and his or her family, community, and health system. Qualitative results demonstrated plausible processes by which peer support improved client engagement in care, cotrimoxazole use, and safe water vessel use. Challenges identified included insufficient messaging surrounding ART initiation, lack of care continuity after ART initiation, rare breaches in confidentiality, and structural challenges. The evaluation found largely positive perceptions of the peer intervention across stakeholders and provided valuable

  5. Multimeric scaffolds displaying the HIV-1 envelope MPER induce MPER-specific antibodies and cross-neutralizing antibodies when co-immunized with gp160 DNA.

    Directory of Open Access Journals (Sweden)

    Shelly J Krebs

    Full Text Available Developing a vaccine that overcomes the diversity of HIV-1 is likely to require a strategy that directs antibody (Ab responses toward conserved regions of the viral Envelope (Env. However, the generation of neutralizing Abs (NAbs targeting these regions through vaccination has proven to be difficult. One conserved region of particular interest is the membrane proximal external region (MPER of Env located within the gp41 ectodomain. In order to direct the immune response to this region, the MPER and gp41 ectodomain were expressed separately as N-terminal fusions to the E2 protein of Geobacillus stearothermophilus. The E2 protein acts as a scaffold by self-assembling into 60-mer particles, displaying up to 60 copies of the fused target on the surface. Rabbits were immunized with E2 particles displaying MPER and/or the gp41 ectodomain in conjunction with DNA encoding full-length gp160. Only vaccines including E2 particles displaying MPER elicited MPER-specific Ab responses. NAbs were elicited after two immunizations that largely targeted the V3 loop. To overcome V3 immunodominance in the DNA component, E2 particles displaying MPER were used in conjunction with gp160 DNA lacking hypervariable regions V2, V3, or combined V1V2V3. All rabbits had HIV binding Ab responses and NAbs following the second vaccination. Using HIV-2/HIV-1 MPER chimeric viruses as targets, NAbs were detected in 12/16 rabbits after three immunizations. Low levels of NAbs specific for Tier 1 and 2 viruses were observed in all groups. This study provides evidence that co-immunizing E2 particles displaying MPER and gp160 DNA can focus Ab responses toward conserved regions of Env.

  6. HLA-C increases HIV-1 infectivity and is associated with gp120

    Directory of Open Access Journals (Sweden)

    Beretta Alberto

    2008-08-01

    Full Text Available Abstract Background A recently identified genetic polymorphism located in the 5' region of the HLA-C gene is associated with individual variations in HIV-1 viral load and with differences in HLA-C expression levels. HLA-C has the potential to restrict HIV-1 by presenting epitopes to cytotoxic T cells but it is also a potent inhibitor of NK cells. In addition, HLA-C molecules incorporated within the HIV-1 envelope have been shown to bind to the envelope glycoprotein gp120 and enhance viral infectivity. We investigated this last property in cell fusion assays where the expression of HLA-C was silenced by small interfering RNA sequences. Syncytia formation was analyzed by co-cultivating cell lines expressing HIV-1 gp120/gp41 from different laboratory and primary isolates with target cells expressing different HIV-1 co-receptors. Virus infectivity was analyzed using pseudoviruses. Molecular complexes generated during cell fusion (fusion complexes were purified and analyzed for their HLA-C content. Results HLA-C positive cells co-expressing HIV-1 gp120/gp41 fused more rapidly and produced larger syncytia than HLA-C negative cells. Transient transfection of gp120/gp41 from different primary isolates in HLA-C positive cells resulted in a significant cell fusion increase. Fusion efficiency was reduced in HLA-C silenced cells compared to non-silenced cells when co-cultivated with different target cell lines expressing HIV-1 co-receptors. Similarly, pseudoviruses produced from HLA-C silenced cells were significantly less infectious. HLA-C was co-purified with gp120 from cells before and after fusion and was associated with the fusion complex. Conclusion Virionic HLA-C molecules associate to Env and increase the infectivity of both R5 and X4 viruses. Genetic polymorphisms associated to variations in HLA-C expression levels may therefore influence the individual viral set point not only by means of a regulation of the virus-specific immune response but also

  7. Implementation and Operational Research: Pulling the Network Together: Quasiexperimental Trial of a Patient-Defined Support Network Intervention for Promoting Engagement in HIV Care and Medication Adherence on Mfangano Island, Kenya.

    Science.gov (United States)

    Hickey, Matthew D; Salmen, Charles R; Omollo, Dan; Mattah, Brian; Fiorella, Kathryn J; Geng, Elvin H; Bacchetti, Peter; Blat, Cinthia; Ouma, Gor B; Zoughbie, Daniel; Tessler, Robert A; Salmen, Marcus R; Campbell, Harold; Gandhi, Monica; Shade, Starley; Njoroge, Betty; Bukusi, Elizabeth A; Cohen, Craig R

    2015-08-01

    Despite progress in the global scale-up of antiretroviral therapy, sustained engagement in HIV care remains challenging. Social capital is an important factor for sustained engagement, but interventions designed to harness this powerful social force are uncommon. We conducted a quasiexperimental study evaluating the impact of the Microclinic Social Network intervention on engagement in HIV care and medication adherence on Mfangano Island, Kenya. The intervention was introduced into 1 of 4 similar communities served by this clinic; comparisons were made between communities using an intention-to-treat analysis. Microclinics, composed of patient-defined support networks, participated in 10 biweekly discussion sessions covering topics ranging from HIV biology to group support and group HIV status disclosure. Nevirapine concentrations in hair were measured before and after study. One hundred thirteen (74%) intervention community participants joined a microclinic group, 86% of whom participated in group HIV status disclosure. Over 22-month follow-up, intervention community participants experienced one-half the rate of ≥ 90-day clinic absence as those in control communities (adjusted hazard ratio: 0.48; 95% confidence interval: 0.25 to 0.92). Nevirapine hair levels declined in both study arms; in adjusted linear regression analysis, the decline was 6.7 ng/mg less severe in the intervention arm than control arm (95% confidence interval: -2.7 to 16.1). The microclinic intervention is a promising and feasible community-based strategy to improve long-term engagement in HIV care and possibly medication adherence. Reducing treatment interruptions using a social network approach has important implications for individual patient virologic suppression, morbidity, and mortality and for broader community empowerment and engagement in healthcare.

  8. Cervical human papillomavirus infection among young women engaged in sex work in Phnom Penh, Cambodia: prevalence, genotypes, risk factors and association with HIV infection

    Directory of Open Access Journals (Sweden)

    Couture Marie-Claude

    2012-07-01

    Full Text Available Abstract Background Although cervical cancer is the leading cancer in Cambodia, most women receive no routine screening for cervical cancer and few treatment options exist. Moreover, nothing is known regarding the prevalence of cervical HPV or the genotypes present among women in the country. Young sexually active women, especially those with multiple sex partners are at highest risk of HPV infection. We examine the prevalence and genotypes of cervical HPV, as well as the associated risk factors among young women engaged in sex work in Phnom Penh, Cambodia. Methods We conducted a cross-sectional study among 220 young women (15–29 years engaged in sex work in different venues including brothels or entertainment establishments, and on a freelance basis in streets, parks and private apartments. Cervical specimens were collected using standard cytobrush technique. HPV DNA was tested for by polymerase chain reaction (PCR and genotyping using type-specific probes for 29 individual HPV types, as well as for a mixture of 10 less common HPV types. All participants were also screened for HIV status using blood samples. Multivariate logistic regression analyses were conducted to assess risk factors for any or multiple HPV infection. Results The prevalence of cervical HPV 41.1%. HPV 51 and 70 were the most common (5.0%, followed by 16 (4.6%, 71 (4.1% and 81 (3.7%. Thirty-six women (16.4% were infected with multiple genotypes and 23.3% were infected with at least one oncogenic HPV type. In multivariate analyses, having HIV infection and a higher number of sexual partners were associated with cervical HPV infection. Risk factors for infection with multiple genotypes included working as freelance female sex workers (FSW or in brothels, recent binge use of drugs, high number of sexual partners, and HIV infection. Conclusions This is the first Cambodian study on cervical HPV prevalence and genotypes. We found that HPV infection was common among young FSW

  9. Insights in Public Health: In What Ways are Hawaii's HIV Prevention Services Engaging Gay Male Couples and Using Technology?

    Science.gov (United States)

    Sophus, Amber I; Fujitani, Loren; Vallabhbhai, Samantha; Antonio, Jo Anna; Yang, Pua Lani; Elliott, Elyssa; Mitchell, Jason W

    2018-02-01

    Partner-oriented services and Health Information and Communication technology (HICT) in the forms of mHealth (eg, smartphone applications), eHealth (eg, interactive websites), telemedicine, and social media play an important and growing role in HIV prevention. Accordingly, the present study sought to describe: (1) the primary and secondary HIV prevention services available in Hawai'i, (2) the prevention services that are available for gay male couples and partners, and (3) the prevention services that use HICT. Information about prevention services and use of HICT were obtained from websites and phone calls made to 19 organizations in the state, including the Hawai'i Department of Health. Overall, partner-oriented services were limited and only 1 couples-based service was currently being offered. Technology, namely social media, was used by 14 organizations, primarily to increase HIV awareness and advertise events. These findings may inform how best to adapt and better leverage the use of innovative technological tools to help expand access to HIV testing and counseling, sexual health education, and case management services for gay male couples and other MSM populations in the state.

  10. HIV testing experiences and their implications for patient engagement with HIV care and treatment on the eve of 'test and treat'

    DEFF Research Database (Denmark)

    Wringe, Alison; Moshabela, Mosa; Nyamukapa, Constance

    2017-01-01

    and engage in care, some delivered static, morally charged messages regarding sexual behaviours and expectations of clinic use which discouraged future care seeking. Repeat testing was commonly reported, reflecting patients’ doubts over the accuracy of prior results and beliefs that antiretroviral therapy...

  11. Engagement of non-government organisations and community care workers in collaborative TB/HIV activities including prevention of mother to child transmission in South Africa: opportunities and challenges.

    Science.gov (United States)

    Uwimana, Jeannine; Zarowsky, Christina; Hausler, Harry; Jackson, Debra

    2012-08-02

    The implementation of collaborative TB/HIV activities may help to mitigate the impact of the dual epidemic on patients and communities. Such implementation requires integrated interventions across facilities and levels of government, and with communities. Engaging Community Care Workers (CCWs) in the delivery of integrated TB/HIV services may enhance universal coverage and treatment outcomes, and address human resource needs in sub-Saharan Africa. Using pre-intervention research in Sisonke district, KwaZulu-Natal, South Africa as a case study, we report on three study objectives: (1) to determine the extent of the engagement of NGOs and CCWs in the implementation of collaborative TB/HIV including PMTCT; (2) to identify constraints related to provision of TB/HIV/PMTCT integrated care at community level; and (3) to explore ways of enhancing the engagement of CCWs to provide integrated TB/HIV/PMTCT services. Our mixed method study included facility and NGO audits, a household survey (n = 3867), 33 key informant interviews with provincial, district, facility, and NGO managers, and six CCW and patient focus group discussions. Most contracted NGOs were providing TB or HIV support and care with little support for PMTCT. Only 11% of facilities' TB and HIV patients needing care and support at the community level were receiving support from CCWs. Only 2% of pregnant women reported being counseled by CCWs on infant feeding options and HIV testing. Most facilities (83%) did not have any structural linkage with NGOs. Major constraints identified were system-related: structural, organizational and managerial constraints; inadequate CCW training and supervision; limited scope of CCW practice; inadequate funding; and inconsistency in supplies and equipment. Individual and community factors, such as lack of disclosure, stigma related to HIV, and cultural beliefs were also identified as constraints. NGO/CCW engagement in the implementation of collaborative TB/HIV/PMTCT activities is

  12. Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France

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    Salmon-Ceron Dominique

    2012-03-01

    Full Text Available Abstract Background Treatment for the hepatitis C virus (HCV may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population. Methods We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600 at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively. Results Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7% had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]. Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians. Conclusions Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.

  13. Chronic Pain, Patient-Physician Engagement, and Family Communication Associated With Drug-Using HIV Patients' Discussing Advanced Care Planning With Their Physicians.

    Science.gov (United States)

    Hansen, Eric D; Mitchell, Mary M; Smith, Tom; Hutton, Nancy; Keruly, Jeanne; Knowlton, Amy R

    2017-10-01

    In the era of effective antiretroviral therapy, persons living with HIV/AIDS (PLWHA) are living longer, transforming HIV into a serious chronic illness, warranting patient-provider discussion about advanced care planning (ACP). Evidence is needed to inform physicians on how to approach ACP for these patients. Chronic pain is common in PLWHA, particularly in those who have substance use disorders; although it is known that this population is at risk for poorer patient-physician engagement, the effects on ACP are unknown. To further characterize factors associated with successful ACP in PLWHA, we examined associations between patient-physician relationship, chronic pain, family communication and problem-solving skills, and rates of patients discussing ACP with their physicians. Data were from the Affirm Care study (N = 325), which examined social and environmental factors associated with health outcomes among PLWHA and their informal caregivers. In multivariate analysis, higher odds of patient reports of discussing ACP with their physicians were associated with their higher rating of their relationship with their physician (adjusted odds ratio [AOR] 1.73; P patients and their physicians should promote patient-centered patient-provider relationships and PLWHAs' family communication and family problem-solving skills. The findings also suggest that PLWHA with chronic pain and prior family discord over end-of-life medical decisions may be primed for ACP. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  14. Evaluation of a male engagement intervention to transform gender norms and improve family planning and HIV service uptake in Kabale, Uganda.

    Science.gov (United States)

    Ghanotakis, Elena; Hoke, Theresa; Wilcher, Rose; Field, Samuel; Mercer, Sarah; Bobrow, Emily A; Namubiru, Mary; Katirayi, Leila; Mandera, Immaculate

    2017-10-01

    Men's limited understanding of family planning (FP) and harmful cultural gender norms pose obstacles to women's FP use. Thirty-two model men called 'Emanzis' were recruited from the community in Kabale, Uganda to lead men from their peer group through a 10-session curriculum designed to transform gender norms and motivate men to engage in FP and HIV services. Cross-sectional surveys were conducted before (n = 1251) and after (n = 1122) implementation. The Gender Equitable Men (GEM) Scale was used to assess the effect on gender attitudes. The intervention achieved negligible changes in responses to GEM items. Improvements in some gender-influenced health-seeking behaviours and practices in men were noted, specifically in visiting health facilities, HIV testing, and condom use. For future application, the intervention should be adapted to require higher peer educator qualifications, longer intervention duration, and more frequent supervision. Practical guidance is needed on where to direct investments in gender-transformative approaches for maximum impact.

  15. Growing the pipeline of diverse HIV investigators: The impact of mentored research experiences to engage underrepresented minority students

    OpenAIRE

    Fuchs, Jonathan; Kouyate, Aminta; Kroboth, Liz; McFarland, Willi

    2016-01-01

    Structured, mentored research programs for high school and undergraduate students from underrepresented minority (URM) backgrounds are needed to increase the diversity of our nation’s biomedical research workforce. In particular, a robust pipeline of investigators from the communities disproportionately affected by the HIV epidemic is needed not only for fairness and equity but for insights and innovations to address persistent racial and ethnic disparities in new infections. We created the S...

  16. Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults.

    Directory of Open Access Journals (Sweden)

    Susan P Buchbinder

    Full Text Available A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg followed by different numbers and intervals of modified vaccinia Ankara Boosts (M. Both vaccines produce virus-like particles presenting membrane-bound Env.Four US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively. Peak immunogenicity was measured 2 weeks post-last vaccination.All regimens were well tolerated and safe. Full dose DgDgM_M and DgDgMM_M regimens generated Env-specific IgG to HIV-1 Env in >90%, IgG3 in >80%, and IgA in <20% of participants. Responses to gp140 and gp41 targets were more common and of higher magnitude than to gp120 and V1V2. The gp41 antibody included reactivity to the conserved immunodominant region with specificities known to mediate virus capture and phagocytosis and did not cross-react with a panel of intestinal flora antigens. The 3rd dose of MVA increased the avidity of elicited antibody (7.5% to 39%, the ADCC response to Bal gp120 (14% to 64%, and the one-year durability of the IgG3 responses to gp41 by 4-fold (13% vs. 3.5% retention of peak response. The co-expressed GM-CSF did not enhance responses over those in trials testing this vaccine without GM-CSF.This DNA/MVA prime-boost regimen induced durable, functional humoral responses that included ADCC, high antibody avidity, and Env IgG1 and IgG3 binding responses to the immunodominant region of gp41. The third, spaced MVA boost improved the overall quality of the antibody response. These products without co-expressed GM-CSF but combined with protein boosts will be considered for efficacy evaluation.ClinicalTrials.gov NCT01571960.

  17. The immediate eff ect of the Same-Sex Marriage Prohibition Act on stigma, discrimination, and engagement on HIV prevention and treatment services in men who have sex with men in Nigeria: analysis of prospective data from the TRUST cohort.

    Science.gov (United States)

    Schwartz, Sheree R; Nowak, Rebecca G; Orazulike, Ifeanyi; Keshinro, Babajide; Ake, Julie; Kennedy, Sara; Njoku, Ogbonnaya; Blattner, William A; Charurat, Manhattan E; Baral, Stefan D

    2015-07-01

    In January, 2014, the Same-Sex Marriage Prohibition Act was signed into law in Nigeria, further criminalising same-sex sexual relationships. We aimed to assess the immediate effect of this prohibition act on stigma, discrimination, and engagement in HIV prevention and treatment services in men who have sex with men (MSM) in Nigeria. The TRUST cohort study uses respondent-driven sampling to assess the feasibility and effectiveness of engagement of MSM in HIV prevention and treatment services at a clinical site located with a community-based organisation trusted by the MSM community. TRUST is a prospective implementation research cohort of MSM (≥16 years) in Abuja, Nigeria. We compared HIV clinical outcomes and stigma, including fear and avoidance of health care, across baseline and quarterly visits before and after implementation of the the Same-Sex Marriage Prohibition Act. Outcomes assessed were measures of stigma and discrimination, loss to follow-up, antiretroviral therapy status, and viral load. We compared outcomes before and after the legislation with χ2 statistics, and estimated incident stigma-related events and loss to follow-up with Poisson regression. Between March 19, 2013, and Aug 7, 2014, 707 MSM participated in baseline study procedures, contributing to 756 before legislation (prelaw) and 420 after legislation (postlaw) visits. Reported history of fear of seeking health care was significantly higher in postlaw visits than in prelaw visits (n=161 [38%] vs n=187 [25%]; psame-sex practices. The negative effects of HIV treatment and care in MSM reinforce the unintended consequences of such legislation on global goals of HIV eradication. Strategies to reach MSM less likely to engage in HIV testing and care in highly stigmatised environments are needed to reduce time to HIV diagnosis and treatment. National Institutes of Health.

  18. Access to healthcare, HIV/STI testing, and preferred pre-exposure prophylaxis providers among men who have sex with men and men who engage in street-based sex work in the US.

    Directory of Open Access Journals (Sweden)

    Kristen Underhill

    Full Text Available Pre-exposure prophylaxis (PrEP is a promising strategy for HIV prevention among men who have sex with men (MSM and men who engage in sex work. But access will require routine HIV testing and contacts with healthcare providers. This study investigated men's healthcare and HIV testing experiences to inform PrEP implementation.We conducted 8 focus groups (n = 38 in 2012 and 56 in-depth qualitative interviews in 2013-14 with male sex workers (MSWs (n = 31 and other MSM (n = 25 in Providence, RI. MSWs primarily met clients in street-based sex work venues. Facilitators asked participants about access to healthcare and HIV/STI testing, healthcare needs, and preferred PrEP providers.MSWs primarily accessed care in emergency rooms (ERs, substance use clinics, correctional institutions, and walk-in clinics. Rates of HIV testing were high, but MSWs reported low access to other STI testing, low insurance coverage, and unmet healthcare needs including primary care, substance use treatment, and mental health services. MSM not engaging in sex work were more likely to report access to primary and specialist care. Rates of HIV testing among these MSM were slightly lower, but they reported more STI testing, more insurance coverage, and fewer unmet needs. Preferred PrEP providers for both groups included primary care physicians, infectious disease specialists, and psychiatrists. MSWs were also willing to access PrEP in substance use treatment and ER settings.PrEP outreach efforts for MSWs and other MSM should engage diverse providers in many settings, including mental health and substance use treatment, ERs, needle exchanges, correctional institutions, and HIV testing centers. Access to PrEP will require financial assistance, but can build on existing healthcare contacts for both populations.

  19. "Facing Our Fears": Using facilitated film viewings to engage communities in HIV research involving MSM in Kenya

    NARCIS (Netherlands)

    Kombo, Bernadette; Sariola, Salla; Gichuru, Evanson; Molyneux, Sassy; Sanders, Eduard J.; van der Elst, Elise

    2017-01-01

    Kenya is a generally homophobic country where homosexuality is criminalised and people who engage in same sex sexuality face stigma and discrimination. In 2013, we developed a 16 min documentary entitled "Facing Our Fears" that aimed at sharing information on how and why men who have sex with men

  20. Humoral Immunogenicity of an HIV-1 Envelope Residue 649-684 Membrane-proximal Region Peptide Fused to the Plague Antigen F1-V

    OpenAIRE

    Matoba, Nobuyuki; Shah, Namrata Rahul; Tsafrir S. Mor

    2011-01-01

    The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR649-684 (F1-V-MPR649-684). We employed systemic im...

  1. Complementation of diverse HIV-1 Env defects through cooperative subunit interactions: a general property of the functional trimer

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    Salzwedel Karl

    2009-08-01

    Full Text Available Abstract Background The HIV-1 Env glycoprotein mediates virus entry by catalyzing direct fusion between the virion membrane and the target cell plasma membrane. Env is composed of two subunits: gp120, which binds to CD4 and the coreceptor, and gp41, which is triggered upon coreceptor binding to promote the membrane fusion reaction. Env on the surface of infected cells is a trimer consisting of three gp120/gp41 homo-dimeric protomers. An emerging question concerns cooperative interactions between the protomers in the trimer, and possible implications for Env function. Results We extended studies on cooperative subunit interactions within the HIV-1 Env trimer, using analysis of functional complementation between coexpressed inactive variants harboring different functional deficiencies. In assays of Env-mediated cell fusion, complementation was observed between variants with a wide range of defects in both the gp120 and gp41 subunits. The former included gp120 subunits mutated in the CD4 binding site or incapable of coreceptor interaction due either to mismatched specificity or V3 loop mutation. Defective gp41 variants included point mutations at different residues within the fusion peptide or heptad repeat regions, as well as constructs with modifications or deletions of the membrane proximal tryptophan-rich region or the transmembrane domain. Complementation required the defective variants to be coexpressed in the same cell. The observed complementation activities were highly dependent on the assay system. The most robust activities were obtained with a vaccinia virus-based expression and reporter gene activation assay for cell fusion. In an alternative system involving Env expression from integrated provirus, complementation was detected in cell fusion assays, but not in virus particle entry assays. Conclusion Our results indicate that Env function does not require every subunit in the trimer to be competent for all essential activities. Through

  2. Gender violence, poverty and HIV infection risk among persons engaged in the sex industry: cross-national analysis of the political economy of sex markets in 30 European and Central Asian countries.

    Science.gov (United States)

    Reeves, A; Steele, S; Stuckler, D; McKee, M; Amato-Gauci, A; Semenza, J C

    2017-11-01

    Persons engaged in the sex industry are at greater risk of HIV and other sexually transmitted infections than the general population. One major factor is exposure to higher levels of risky sexual activity. Expanding condom use is a critical prevention strategy, but this requires negotiation with those buying sex, which takes place in the context of cultural and economic constraints. Impoverished individuals who fear violence are more likely to forego condoms. Here we tested the hypotheses that poverty and fear of violence are two structural drivers of HIV infection risk in the sex industry. Using data from the European Centre for Disease Prevention and Control and the World Bank for 30 countries, we evaluated poverty, measured using the average income per day per person in the bottom 40% of the income distribution, and gender violence, measured using homicide rates in women and the proportion of women exposed to violence in the last 12 months and/or since age 16 years. We found that HIV prevalence among those in the sex industry was higher in countries where there were greater female homicide rates (β = 0.86; P = 0.018) and there was some evidence that self-reported exposure to violence was also associated with higher HIV prevalence (β = 1.37; P = 0.043). Conversely, HIV prevalence was lower in countries where average incomes among the poorest were greater (β = -1.05; P = 0.046). Our results are consistent with the theory that reducing poverty and exposure to violence may help reduce HIV infection risk among persons engaged in the sex industry. © 2017 British HIV Association.

  3. Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

    Science.gov (United States)

    Denner, Joachim

    2013-01-01

    The induction of neutralizing antibodies is a promising way to prevent retrovirus infections. Neutralizing antibodies are mainly directed against the envelope proteins, which consist of two molecules, the surface envelope (SU) protein and the transmembrane envelope (TM) protein. Antibodies broadly neutralizing the human immunodeficiencvy virus-1 (HIV-1) and binding to the TM protein gp41 of the virus have been isolated from infected individuals. Their epitopes are located in the membrane proximal external region (MPER). Since there are difficulties to induce such neutralizing antibodies as basis for an effective AIDS vaccine, we performed a comparative analysis immunising with the TM proteins of different viruses from the family Retroviridae. Both subfamilies, the Orthoretrovirinae and the Spumaretrovirinae were included. In this study, the TM proteins of three gammaretroviruses including (1) the porcine endogenous retrovirus (PERV), (2) the Koala retrovirus (KoRV), (3) the feline leukemia virus (FeLV), of two lentiviruses, HIV-1, HIV-2, and of two spumaviruses, the feline foamy virus (FFV) and the primate foamy virus (PFV) were used for immunisation. Whereas in all immunisation studies binding antibodies were induced, neutralizing antibodies were only found in the case of the gammaretroviruses. The induced antibodies were directed against the MPER and the fusion peptide proximal region (FPPR) of their TM proteins; however only the antibodies against the MPER were neutralizing. Most importantly, the epitopes in the MPER were localized in the same position as the epitopes of the antibodies broadly neutralizing HIV-1 in the TM protein gp41 of HIV-1, indicating that the MPER is an effective target for the neutralization of retroviruses. PMID:23249763

  4. The role of blood cell membrane lipids on the mode of action of HIV-1 fusion inhibitor sifuvirtide

    Energy Technology Data Exchange (ETDEWEB)

    Matos, Pedro M.; Freitas, Teresa; Castanho, Miguel A.R.B. [Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal); Santos, Nuno C., E-mail: nsantos@fm.ul.pt [Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal)

    2010-12-17

    Research highlights: {yields} Sifuvirtide interacts with erythrocyte and lymphocyte membrane in a concentration dependent manner by decreasing its dipole potential. {yields} Dipole potential variations in lipid vesicles show sifuvirtide's lipid selectivity towards saturated phosphatidylcholines. {yields} This peptide-membrane interaction may direct the drug towards raft-like membrane domains where the receptors used by HIV are located, facilitating its inhibitory action. -- Abstract: Sifuvirtide is a gp41 based peptide that inhibits HIV-1 fusion with the host cells and is currently under clinical trials. Previous studies showed that sifuvirtide partitions preferably to saturated phosphatidylcholine lipid membranes, instead of fluid-phase lipid vesicles. We extended the study to the interaction of the peptide with circulating blood cells, by using the dipole potential sensitive probe di-8-ANEPPS. Sifuvirtide decreased the dipole potential of erythrocyte and lymphocyte membranes in a concentration dependent manner, demonstrating its interaction. Also, the lipid selectivity of the peptide towards more rigid phosphatidylcholines was confirmed based on the dipole potential variations. Overall, the interaction of the peptide with the cell membranes is a contribution of different lipid preferences that presumably directs the peptide towards raft-like domains where the receptors are located, facilitating the reach of the peptide to its molecular target, the gp41 in its pre-fusion conformation.

  5. Enhanced mucosal and systemic immune response with intranasal immunization of mice with HIV peptides entrapped in PLG microparticles in combination with Ulex Europaeus-I lectin as M cell target.

    Science.gov (United States)

    Manocha, Monika; Pal, Pramod Chandra; Chitralekha, K T; Thomas, Beena Elizabeth; Tripathi, Vinita; Gupta, Siddhartha Dutta; Paranjape, Ramesh; Kulkarni, Smita; Rao, D Nageswara

    2005-12-01

    The predominant route of HIV infection is through the sexual transmission via M cells. Most of the peptide and protein vaccines show poor transport across the epithelial barrier and are commonly administered by parenteral route. In the present study four HIV peptides from envelope (gp 41-LZ (leucine zipper), gp 41-FD (fusion domain) and gp120-C2) and regulatory (Nef) region in poly lactic-co-glycolide (PLG) micro-particle delivery were evaluated in mice of outbred and with different genetic background to compare immune response versus MHC restriction. Out of the combinational and single routes of immunization attempted, the single route maintained the IgG, IgA and sIgA in sera and washes for longer duration as compared to combinational routes in which the response was declined. The study demonstrated that single intranasal immunization offered significantly higher immune response (pPP>or=SP. The cytokine measurement profile of IL-2, IFN-gamma and IL-6 and low levels of IL-4 in the cultural supernatants of SP, PP and LP showed mixed CD4(+) Th1 and Th2 immune response. The p24 assay showed high percent inhibition of HIV-IIIB virus with sera and washes obtained from intranasal route. Thus, overall the study highlighted the combination of UEA-1 lectin with HIV peptides in micro-particles through intranasal immunization generated systemic as well as mucosal immune response.

  6. Serotyping and genotyping of HIV-1 infection in residents of Khayelitsha, Cape Town, South Africa.

    Science.gov (United States)

    Jacobs, G B; de Beer, C; Fincham, J E; Adams, V; Dhansay, M A; van Rensburg, E Janse; Engelbrecht, S

    2006-12-01

    It is estimated that between 5.5 and 6.1 million people are infected with HIV/acquired immunodeficiency syndrome (AIDS) in South Africa, with subtype C responsible for the majority of these infections. The Khayelitsha suburb of Cape Town has one of the highest HIV prevalence rates in South Africa. Overcrowding combined with unemployment and crime in parts of the area perpetuates high-risk sexual behavior, which increases exposure to infection by HIV. Against this background, the objective of this study was to characterize HIV-1 in residents confirmed to be seropositive. Serotyping was performed through a competitive enzyme-linked immunosorbent assay (cPEIA). Genotyping methods included RNA isolation followed by RT-PCR and sequencing of the gag p24, env gp41 immunodominant region (IDR), and env gp120 V3 genome regions of HIV-1. With the exception of a possible C/D recombinant strain, all HIV-1 strains were characterized as HIV-1 group M subtype C. One individual was shown to harbor multiple strains of HIV-1 subtype C. In Southern Africa, the focus has been to develop a subtype C candidate vaccine, as this is the major subtype found in this geographical area. Therefore, the spread of HIV-1 and its recombinant strains needs to be monitored closely. (c) 2006 Wiley-Liss, Inc.

  7. GB Virus Type C Envelope Protein E2 Elicits Antibodies That React with a Cellular Antigen on HIV-1 Particles and Neutralize Diverse HIV-1 Isolates

    Science.gov (United States)

    Mohr, Emma L.; Xiang, Jinhua; McLinden, James H.; Kaufman, Thomas M.; Chang, Qing; Montefiori, David C.; Klinzman, Donna; Stapleton, Jack T.

    2012-01-01

    Broadly neutralizing Abs to HIV-1 are well described; however, identification of Ags that elicit these Abs has proven difficult. Persistent infection with GB virus type C (GBV-C) is associated with prolonged survival in HIV-1–infected individuals, and among those without HIV-1 viremia, the presence of Ab to GBV-C glycoprotein E2 is also associated with survival. GBV-C E2 protein inhibits HIV-1 entry, and an antigenic peptide within E2 interferes with gp41-induced membrane perturbations in vitro, suggesting the possibility of structural mimicry between GBV-C E2 protein and HIV-1 particles. Naturally occurring human and experimentally induced GBV-C E2 Abs were examined for their ability to neutralize infectious HIV-1 particles and HIV-1–enveloped pseudovirus particles. All GBV-C E2 Abs neutralized diverse isolates of HIV-1 with the exception of rabbit anti-peptide Abs raised against a synthetic GBV-C E2 peptide. Rabbit anti–GBV-C E2 Abs neutralized HIV-1–pseudotyped retrovirus particles but not HIV-1–pseudotyped vesicular stomatitis virus particles, and E2 Abs immune-precipitated HIV-1 gag particles containing the vesicular stomatitis virus type G envelope, HIV-1 envelope, GBV-C envelope, or no viral envelope. The Abs did not neutralize or immune-precipitate mumps or yellow fever viruses. Rabbit GBV-C E2 Abs inhibited HIV attachment to cells but did not inhibit entry following attachment. Taken together, these data indicate that the GBV-C E2 protein has a structural motif that elicits Abs that cross-react with a cellular Ag present on retrovirus particles, independent of HIV-1 envelope glycoproteins. The data provide evidence that a heterologous viral protein can induce HIV-1–neutralizing Abs. PMID:20826757

  8. Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies.

    Science.gov (United States)

    Bouvin-Pley, M; Morgand, M; Meyer, L; Goujard, C; Moreau, A; Mouquet, H; Nussenzweig, M; Pace, C; Ho, D; Bjorkman, P J; Baty, D; Chames, P; Pancera, M; Kwong, P D; Poignard, P; Barin, F; Braibant, M

    2014-12-01

    Extending our previous analyses to the most recently described monoclonal broadly neutralizing antibodies (bNAbs), we confirmed a drift of HIV-1 clade B variants over 2 decades toward higher resistance to bNAbs targeting almost all the identified gp120-neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 membrane-proximal external region remained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable of neutralizing efficiently most of the circulating variants. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  9. The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Peter D. Burbelo

    2012-01-01

    Full Text Available Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP, Kaposi's sarcoma (KS, or non-Hodgkin lymphoma (NHL. Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84% showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94% in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.

  10. Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate.

    Directory of Open Access Journals (Sweden)

    Elizabeth Stansell

    Full Text Available As HIV-1-encoded envelope protein traverses the secretory pathway, it may be modified with N- and O-linked carbohydrate. When the gp120s of HIV-1 NL4-3, HIV-1 YU2, HIV-1 Bal, HIV-1 JRFL, and HIV-1 JRCSF were expressed as secreted proteins, the threonine at consensus position 499 was found to be O-glycosylated. For SIVmac239, the corresponding threonine was also glycosylated when gp120 was recombinantly expressed. Similarly-positioned, highly-conserved threonines in the influenza A virus H1N1 HA1 and H5N1 HA1 envelope proteins were also found to carry O-glycans when expressed as secreted proteins. In all cases, the threonines were modified predominantly with disialylated core 1 glycans, together with related core 1 and core 2 structures. Secreted HIV-1 gp140 was modified to a lesser extent with mainly monosialylated core 1 O-glycans, suggesting that the ectodomain of the gp41 transmembrane component may limit the accessibility of Thr499 to glycosyltransferases. In striking contrast to these findings, gp120 on purified virions of HIV-1 Bal and SIV CP-MAC lacked any detectable O-glycosylation of the C-terminal threonine. Our results indicate the absence of O-linked carbohydrates on Thr499 as it exists on the surface of virions and suggest caution in the interpretation of analyses of post-translational modifications that utilize recombinant forms of envelope protein.

  11. Recombinant viruses initiated the early HIV-1 epidemic in Burkina Faso.

    Directory of Open Access Journals (Sweden)

    Peter N Fonjungo

    Full Text Available We analyzed genetic diversity and phylogenetic relationships among 124 HIV-1 and 19 HIV-2 strains in sera collected in 1986 from patients of the state hospital in Ouagadougou, Burkina Faso. Phylogenetic analysis of the HIV-1 env gp41 region of 65 sequences characterized 37 (56.9% as CRF06_cpx strains, 25 (38.5% as CRF02_AG, 2 (3.1% as CRF09_cpx, and 1 (1.5% as subtype A. Similarly, phylogenetic analysis of the protease (PR gene region of 73 sequences identified 52 (71.2% as CRF06_cpx, 15 (20.5% as CRF02_AG, 5 (6.8% as subtype A, and 1 (1.4% was a unique strain that clustered along the B/D lineage but basal to the node connecting the two lineages. HIV-2 PR or integrase (INT groups A (n = 17 [89.5%] and B (n = 2 [10.5%] were found in both monotypic (n = 11 and heterotypic HIV-1/HIV-2 (n = 8 infections, with few HIV-2 group B infections. Based on limited available sampling, evidence suggests two recombinant viruses, CRF06_cpx and CRF02_AG, appear to have driven the beginning of the mid-1980s HIV-1 epidemic in Burkina Faso.

  12. Engaging Stakeholder Engagement

    OpenAIRE

    Wilhite, Ryan; Pyrz, Jennifer

    2017-01-01

    The Indianapolis Metropolitan Planning Organization is setting the bar for effective public and stakeholder engagement with its current update of the Long Range Transportation Plan. MPO staff are soliciting feedback at each step of the planning process— from development of goals, objectives, and performance measures to scenario planning. In this session we share strategies and lessons learned for effective engagement throughout the planning process.

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... influence of drugs and alcohol engaged in risky sexual behavior that resulted in HIV infection. Watch the "After ... poor decision making, which can result in risky sexual behaviors and HIV infection. Although the characters are fictional, ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... 1 Some hopeful news is that, in recent years, HIV is no longer a death sentence, as ... contracting HIV. In general, middle and late teen years are when young people engage in risk-taking ...

  15. Drogas anti-VIH: passado, presente e perspectivas futuras Drugs anti-HIV: past, present and future perspectives

    Directory of Open Access Journals (Sweden)

    Marcus Vinícius Nora de Souza

    2003-05-01

    Full Text Available Currently available anti-HIV drugs can be classified into three categories: nucleoside analogue reverse transcriptase inhibitors (NRTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs and protease inhibitors (PIs. In addition to the reverse transcriptase (RT and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (1 viral adsorption, through binding to the viral envelope glycoprotein gp120; (2 viral entry, through blockage of the viral coreceptors CXCR4 and CCR5; (3 virus-cell fusion, through binding to the viral envelope glycoprotein gp 41; (4 viral assembly and disassembly through NCp7 zinc finger-targeted agents; (5 proviral DNA integration, through integrase inhibitors and (6 viral mRNA transcription, through inhibitors of the transcription (transactivation process. Also, various new NRTIs, NNRTIs and PIs have been developed, possessing different improved characteristics.

  16. Solid-state nuclear magnetic resonance measurements of HIV fusion peptide 13CO to lipid 31P proximities support similar partially inserted membrane locations of the α helical and β sheet peptide structures.

    Science.gov (United States)

    Gabrys, Charles M; Qiang, Wei; Sun, Yan; Xie, Li; Schmick, Scott D; Weliky, David P

    2013-10-03

    Fusion of the human immunodeficiency virus (HIV) membrane and the host cell membrane is an initial step of infection of the host cell. Fusion is catalyzed by gp41, which is an integral membrane protein of HIV. The fusion peptide (FP) is the ∼25 N-terminal residues of gp41 and is a domain of gp41 that plays a key role in fusion catalysis likely through interaction with the host cell membrane. Much of our understanding of the FP domain has been accomplished with studies of "HFP", i.e., a ∼25-residue peptide composed of the FP sequence but lacking the rest of gp41. HFP catalyzes fusion between membrane vesicles and serves as a model system to understand fusion catalysis. HFP binds to membranes and the membrane location of HFP is likely a significant determinant of fusion catalysis perhaps because the consequent membrane perturbation reduces the fusion activation energy. In the present study, many HFPs were synthesized and differed in the residue position that was (13)CO backbone labeled. Samples were then prepared that each contained a singly (13)CO labeled HFP incorporated into membranes that lacked cholesterol. HFP had distinct molecular populations with either α helical or oligomeric β sheet structure. Proximity between the HFP (13)CO nuclei and (31)P nuclei in the membrane headgroups was probed by solid-state NMR (SSNMR) rotational-echo double-resonance (REDOR) measurements. For many samples, there were distinct (13)CO shifts for the α helical and β sheet structures so that the proximities to (31)P nuclei could be determined for each structure. Data from several differently labeled HFPs were then incorporated into a membrane location model for the particular structure. In addition to the (13)CO labeled residue position, the HFPs also differed in sequence and/or chemical structure. "HFPmn" was a linear peptide that contained the 23 N-terminal residues of gp41. "HFPmn_V2E" contained the V2E mutation that for HIV leads to greatly reduced extent of fusion and

  17. Solid-State Nuclear Magnetic Resonance Measurements of HIV Fusion Peptide 13CO to Lipid 31P Proximities Support Similar Partially Inserted Membrane Locations of the α Helical and β Sheet Peptide Structures

    Science.gov (United States)

    Gabrys, Charles M.; Qiang, Wei; Sun, Yan; Xie, Li; Schmick, Scott D.; Weliky, David P.

    2013-10-01

    Fusion of the human immunodeficiency virus (HIV) membrane and the host cell membrane is an initial step of infection of the host cell. Fusion is catalyzed by gp41, which is an integral membrane protein of HIV. The fusion peptide (FP) is the -25 N-terminal residues of gp41 and is a domain of gp41 that plays a key role in fusion catalysis likely through interaction with the host cell membrane. Much of our understanding of the FP domain has been accomplished with studies of -HFP-, i.e., a -25-residue peptide composed of the FP sequence but lacking the rest of gp41. HFP catalyzes fusion between membrane vesicles and serves as a model system to understand fusion catalysis. HFP binds to membranes and the membrane location of HFP is likely a significant determinant of fusion catalysis perhaps because the consequent membrane perturbation reduces the fusion activation energy. In the present study, many HFPs were synthesized and differed in the residue position that was 13CO backbone labeled. Samples were then prepared that each contained a singly 13CO labeled HFP incorporated into membranes that lacked cholesterol. HFP had distinct molecular populations with either α helical or oligomeric - sheet structure. Proximity between the HFP 13CO nuclei and 31P nuclei in the membrane headgroups was probed by solid-state NMR (SSNMR) rotational-echo double-resonance (REDOR) measurements. For many samples, there were distinct 13CO shifts for the α helical and - sheet structures so that the proximities to 31P nuclei could be determined for each structure. Data from several differently labeled HFPs were then incorporated into a membrane location model for the particular structure. In addition to the 13CO labeled residue position, the HFPs also differed in sequence and/or chemical structure. -HFPmn- was a linear peptide that contained the 23 N-terminal residues of gp41. -HFPmn_V2E- contained the V2E mutation that for HIV leads to greatly reduced extent of fusion and infection. The

  18. Lessons learnt from promising practices in community engagement for the elimination of new HIV infections in children by 2015 and keeping their mothers alive: summary of a desk review.

    Science.gov (United States)

    Ackerman Gulaid, Laurie; Kiragu, Karusa

    2012-07-11

    Through the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping their Mothers Alive, leaders have called for broader action to strengthen the involvement of communities. The Global Plan aspires to reduce new HIV infections among children by 90 percent, and to reduce AIDS-related maternal mortality by half. This article summarizes the results of a review commissioned by UNAIDS to help inform stakeholders on promising practices in community engagement to accelerate progress towards these ambitious goals. This research involved extensive literature review and key informant interviews. Community engagement was defined to include participation, mobilization and empowerment while excluding activities that involve communities solely as service recipients. A promising practice was defined as one for which there is documented evidence of its effectiveness in achieving intended results and some indication of replicability, scale up and/or sustainability. Promising practices that increased the supply of preventing mother-to-child transmission (PMTCT) services included extending community cadres, strengthening linkages with community- and faith-based organizations and civic participation in programme monitoring. Practices to improve demand for PMTCT included community-led social and behaviour change communication, peer support and participative approaches to generate local solutions. Practices to create an enabling environment included community activism and government leadership for greater involvement of communities. Committed leadership at all levels, facility, community, district and national, is crucial to success. Genuine community engagement requires a rights-based, capacity-building approach and sustained financial and technical investment. Participative formative research is a first step in building community capacity and helps to ensure programme relevance. Building on existing structures, rather than working in parallel to

  19. HIV-1 diversity in an antiretroviral treatment naïve cohort from Bushbuckridge, Mpumalanga Province, South Africa.

    Science.gov (United States)

    Msimanga, Patrick Wela; Vardas, Efthyia; Engelbrecht, Susan

    2015-02-13

    South Africa has a generalized and explosive HIV/AIDS epidemic with the largest number of people infected with HIV-1 in the world. Molecular investigations of HIV-1 diversity can help enhance interventions to contain and combat the HIV/AIDS epidemic. However, many studies of HIV-1 diversity in South Africa tend to be limited to the major metropolitan centers and their surrounding provinces. Hardly any studies of HIV diversity have been undertaken in Mpumalanga Province, and this study sought to investigate the HIV-1 diversity in this province, as well as establish the occurrence and extent of transmitted antiretroviral drug resistance mutations. HIV-1 gag p24, pol p10 and p66/p51, pol p31 and env gp41 gene fragments from 43 participants were amplified and sequenced. Quality control on the sequences was carried out using the LANL QC online tool. HIV-1 subtype was preliminary assigned using the REGA 3.0 and jpHMM online tools. Subtype for the pol gene fragment was further designated using the SCUEAL online tool. Phylogenetic analysis was inferred using the Maximum Likelihood methods in MEGA version 6. HIV-1 antiretroviral drug resistance mutations were determined using the Stanford database. Phylogenetic analysis using Maximum Likelihood methods indicated that all sequences in the study clustered with HIV-1 subtype C. The exception was one putative subtype BC unique recombinant form. Antiretroviral drug resistance mutations K103N and E138A were also detected, indicating possible transmission of anti-retroviral drug resistance mutations. The phylogenetic analysis of the HIV sequences revealed that, by 2009, patients in the Bushbuckridge, Mpumalanga were predominantly infected with HIV-1 subtype C. However, the generalized, explosive nature of the HIV/AIDS epidemic in South Africa, in the context of extensive mobility by South Africans who inhabit rural areas, renders the continued molecular monitoring and surveillance of the epidemic imperative.

  20. A Lipopeptide HIV-1/2 Fusion Inhibitor with Highly Potent In Vitro, Ex Vivo, and In Vivo Antiviral Activity.

    Science.gov (United States)

    Chong, Huihui; Xue, Jing; Xiong, Shengwen; Cong, Zhe; Ding, Xiaohui; Zhu, Yuanmei; Liu, Zixuan; Chen, Ting; Feng, Yifan; He, Lei; Guo, Yan; Wei, Qiang; Zhou, Yusen; Qin, Chuan; He, Yuxian

    2017-06-01

    Peptides derived from the C-terminal heptad repeat (CHR) region of the human immunodeficiency virus type 1 (HIV-1) fusogenic protein gp41 are potent viral entry inhibitors, and currently, enfuvirtide (T-20) is the only one approved for clinical use; however, emerging drug resistance largely limits its efficacy. In this study, we generated a novel lipopeptide inhibitor, named LP-19, by integrating multiple design strategies, including an N-terminal M-T hook structure, an HIV-2 sequence, intrahelical salt bridges, and a membrane-anchoring lipid tail. LP-19 showed stable binding affinity and highly potent, broad, and long-lasting antiviral activity. In in vitro studies, LP-19 efficiently inhibited HIV-1-, HIV-2-, and simian immunodeficiency virus (SIV)-mediated cell fusion, viral entry, and infection, and it was highly active against diverse subtypes of primary HIV-1 isolates and inhibitor-resistant mutants. Ex vivo studies demonstrated that LP-19 exhibited dramatically increased anti-HIV activity and an extended half-life in rhesus macaques. In short-term monotherapy, LP-19 reduced viral loads to undetectable levels in acutely and chronically simian-human immunodeficiency virus (SHIV)-infected monkeys. Therefore, this study offers an ideal HIV-1/2 fusion inhibitor for clinical development and emphasizes the importance of the viral fusion step as a drug target.IMPORTANCE The peptide drug T-20 is the only viral fusion inhibitor in the clinic, which is used for combination therapy of HIV-1 infection; however, it requires a high dosage and easily induces drug resistance, calling for a new drug with significantly improved pharmaceutical profiles. Here, we have developed a short-lipopeptide-based fusion inhibitor, termed LP-19, which mainly targets the conserved gp41 pocket site and shows highly potent inhibitory activity against HIV-1, HIV-2, and even SIV isolates. LP-19 exhibits dramatically increased antiviral activity and an extended half-life in rhesus macaques, and

  1. CD4-gp120 interaction interface - a gateway for HIV-1 infection in human: molecular network, modeling and docking studies.

    Science.gov (United States)

    Pandey, Deeksha; Podder, Avijit; Pandit, Mansi; Latha, Narayanan

    2017-09-01

    The major causative agent for Acquired Immune Deficiency Syndrome (AIDS) is Human Immunodeficiency Virus-1 (HIV-1). HIV-1 is a predominant subtype of HIV which counts on human cellular mechanism virtually in every aspect of its life cycle. Binding of viral envelope glycoprotein-gp120 with human cell surface CD4 receptor triggers the early infection stage of HIV-1. This study focuses on the interaction interface between these two proteins that play a crucial role for viral infectivity. The CD4-gp120 interaction interface has been studied through a comprehensive protein-protein interaction network (PPIN) analysis and highlighted as a useful step towards identifying potential therapeutic drug targets against HIV-1 infection. We prioritized gp41, Nef and Tat proteins of HIV-1 as valuable drug targets at early stage of viral infection. Lack of crystal structure has made it difficult to understand the biological implication of these proteins during disease progression. Here, computational protein modeling techniques and molecular dynamics simulations were performed to generate three-dimensional models of these targets. Besides, molecular docking was initiated to determine the desirability of these target proteins for already available HIV-1 specific drugs which indicates the usefulness of these protein structures to identify an effective drug combination therapy against AIDS.

  2. Engagement of Gay Men and Other Men Who Have Sex with Men (MSM) in the Response to HIV: A Critical Step in Achieving an AIDS-Free Generation.

    Science.gov (United States)

    Stahlman, Shauna; Beyrer, Chris; Sullivan, Patrick S; Mayer, Kenneth H; Baral, Stefan D

    2016-12-01

    Men who have sex with men (MSM) continue to be at elevated risk for HIV acquisition and transmission secondary to biological and behavioral characteristics, social and sexual network characteristics, community environmental factors, and structural factors. HIV incidence rates remain high among MSM in both low- and high-income settings, and in both concentrated and more generalized HIV epidemic settings. While data quality tends to be poorer, the best estimates collectively suggest that MSM have up to 20 times the odds of living with HIV as compared to other reproductive aged adults across low- and middle-income countries. Recent prevention strategies to lower biological HIV transmission and acquisition risks, including the early use of antiretrovirals to decrease infectiousness for those living with HIV, and pre-exposure prophylaxis for those at significant risk of HIV acquisition, have demonstrated the potential to change the trajectory of the HIV epidemics among MSM. However, the coverage and effectiveness of these approaches is limited by structural factors including the punitive legal frameworks and institutional discrimination that contribute to limited uptake, challenges to adherence, and suboptimal health-seeking behaviors among MSM. More intensive efforts will be required to reach MSM who do not currently have access to relevant and effective prevention and treatment services or elect not to access these services given enacted and/or perceived stigma. Respect for human rights, including efforts to aggressively confront and combat the forms of stigma that are preventing us from achieving an AIDS-Free generation, are needed for all people including gay men and other MSM.

  3. The characteristics of screening and confirmatory test results for HIV in Xi'an, China.

    Science.gov (United States)

    Wang, Linchuan; Zhou, Kai-Hua; Zhao, He-Ping; Wang, Ji-Han; Zheng, Hai-Chao; Yu, Yan; Chen, Wei

    2017-01-01

    Individuals with recent or acute HIV infection are more infectious than those with established infection. Our objective was to analyze the characteristics of detection among HIV infections in Xi'an. A 4th-generation kit (Architect HIV Ag/Ab Combo) and three 3rd-generationEIA kits (WanTai, XinChuang and Livzon) were used for HIV screening. Overall, 665 individuals were identified as positive and were tested by western blotting (WB). The characteristics of the screening and confirmatory tests were analyzed, including the band patterns, the early detection performance and the false-positive rates. In total, 561 of the 665 patients were confirmed as having HIV-1 infection, and no HIV-2 specific band was observed. Among these 561 WB-positive cases, reactivity to greater than or equal to 9 antigens was the most commonly observed pattern (83.18%), and the absence of reactivity to p17, p31 and gp41 was detected in 6.44%, 5.9% and 2.86% of the cases, respectively. Two cases were positive by the 4th-generation assay but negative by the 3rd-generation assay for HIV screening and had seroconversion. The false-positive rate of the Architect HIV Ag/Ab Combo (22.01%) was significantly higher than those of WanTai (9.88%), XinChuang (10.87%) and Livzon (8.93%), pHIV infection in Xi'an is mainly caused by HIV-1, and individuals are rarely identified at the early phase. Although the false-positive rate of the 4th-generation assay was higher than that of the 3rd-generation assay, it is still recommended for use as the initial HIV screening test for high-risk individuals. In Xi'an, a 3rd-generation assay for screening could be considered.

  4. The characteristics of screening and confirmatory test results for HIV in Xi'an, China.

    Directory of Open Access Journals (Sweden)

    Linchuan Wang

    Full Text Available Individuals with recent or acute HIV infection are more infectious than those with established infection. Our objective was to analyze the characteristics of detection among HIV infections in Xi'an.A 4th-generation kit (Architect HIV Ag/Ab Combo and three 3rd-generationEIA kits (WanTai, XinChuang and Livzon were used for HIV screening. Overall, 665 individuals were identified as positive and were tested by western blotting (WB. The characteristics of the screening and confirmatory tests were analyzed, including the band patterns, the early detection performance and the false-positive rates.In total, 561 of the 665 patients were confirmed as having HIV-1 infection, and no HIV-2 specific band was observed. Among these 561 WB-positive cases, reactivity to greater than or equal to 9 antigens was the most commonly observed pattern (83.18%, and the absence of reactivity to p17, p31 and gp41 was detected in 6.44%, 5.9% and 2.86% of the cases, respectively. Two cases were positive by the 4th-generation assay but negative by the 3rd-generation assay for HIV screening and had seroconversion. The false-positive rate of the Architect HIV Ag/Ab Combo (22.01% was significantly higher than those of WanTai (9.88%, XinChuang (10.87% and Livzon (8.93%, p<0.05.HIV infection in Xi'an is mainly caused by HIV-1, and individuals are rarely identified at the early phase. Although the false-positive rate of the 4th-generation assay was higher than that of the 3rd-generation assay, it is still recommended for use as the initial HIV screening test for high-risk individuals. In Xi'an, a 3rd-generation assay for screening could be considered.

  5. Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.

    Directory of Open Access Journals (Sweden)

    James Friedman

    Full Text Available Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody responses may play a role in protection of the majority of HIV-exposed, breastfeeding infants. Therefore, characterization of HIV-specific antibodies produced by B cells in milk could guide the development of vaccines that elicit protective mucosal antibody responses.We isolated B cells from colostrum of an HIV-infected lactating woman with a detectable neutralization response in milk and recombinantly produced and characterized the resulting HIV-1 Envelope (Env-specific monoclonal antibodies (mAbs.The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i gp120-specific mAb with moderate breadth of neutralization.These novel HIV-neutralizing mAbs isolated from a mucosal compartment provide insight into the ability of mucosal B cell populations to produce functional anti-HIV antibodies that may contribute to protection against virus acquisition at mucosal surfaces.

  6. Sexual HIV risk among substance-using female commercial sex ...

    African Journals Online (AJOL)

    Sexual HIV risk among substance-using female commercial sex workers in ... risk for HIV (defined as engaging in unprotected sex with sexual partners in the past ... previously been diagnosed with HIV or a sexually transmitted disease (STD) ...

  7. Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses.

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    Full Text Available The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV.Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPER-displaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested.Optimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection.

  8. Development of potent and long-acting HIV-1 fusion inhibitors.

    Science.gov (United States)

    Chong, Huihui; Wu, Xiyuan; Su, Yang; He, Yuxian

    2016-05-15

    T20 (enfuvirtide) is the first approved HIV entry inhibitor and currently the only viral fusion inhibitor, but its low efficacy and genetic barrier to resistance significantly limit its application, calling for a next-generation drug. On the basis of the M-T hook structure, we recently developed a short-peptide named HP23, which mainly targets the deep pocket site of gp41 and possesses highly potent antiviral activity. To improve the pharmaceutical properties of a peptide-based inhibitor, we modified HP23 by different classes of lipids including fatty acid, cholesterol, and sphingolipids. To avoid the potential problem of oxidation, the methionine residue in the M-T hook sequence of HP23 was replaced with leucine. Peptides were synthesized and their anti-HIV activity and biophysical properties were determined. A group of lipopeptides were generated with greatly improved anti-HIV activity. Promisingly, a fatty acid-conjugated lipopeptide named LP-11 showed potent and broad inhibitory activity against diverse primary HIV-1 isolates and clinically drug-resistant mutants, and it had dramatically increased ex-vivo antiviral activity and extended half-life. Also, LP-11 displayed highly enhanced α-helicity and thermal stability, and it was physically stable under high temperature and humidity. LP-11 has high potentials for clinical development and it can serve as an ideal tool for exploring the mechanisms of HIV-1 fusion and inhibition.

  9. Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory; Fischer, William [Los Alamos National Laboratory; Wallstrom, Timothy [Los Alamos National Laboratory

    2009-01-01

    An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. Synthetic mosaic HIV -I antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T -cell-based HIV -1 vaccines.

  10. Chimeric Rhinoviruses Displaying MPER Epitopes Elicit Anti-HIV Neutralizing Responses

    Science.gov (United States)

    Yi, Guohua; Lapelosa, Mauro; Bradley, Rachel; Mariano, Thomas M.; Dietz, Denise Elsasser; Hughes, Scott; Wrin, Terri; Petropoulos, Chris; Gallicchio, Emilio; Levy, Ronald M.; Arnold, Eddy; Arnold, Gail Ferstandig

    2013-01-01

    Background The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER) of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV. Methodology/Principle Findings Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV) displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPER-displaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested. Conclusions Optimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection. PMID:24039745

  11. The effect of engaging unpaid informal providers on case detection and treatment initiation rates for TB and HIV in rural Malawi (Triage Plus): A cluster randomised health system intervention trial.

    Science.gov (United States)

    Bello, George; Faragher, Brian; Sanudi, Lifah; Namakhoma, Ireen; Banda, Hastings; Malmborg, Rasmus; Thomson, Rachael; Squire, S Bertel

    2017-01-01

    The poor face barriers in accessing services for tuberculosis (TB) and Human Immuno-deficiency Virus (HIV) disease. A cluster randomised trial was conducted to investigate the effectiveness of engaging unpaid informal providers (IPs) to promote access in a rural district. The intervention consisted of training unpaid IPs in TB and HIV disease recognition, sputum specimen collection, appropriate referrals, and raising community awareness. In total, six clusters were defined in the study areas. Through a pair-matched cluster randomization process, three clusters (average cluster population = 200,714) were allocated to receive the intervention in the Early arm. Eleven months later the intervention was rolled out to the remaining three clusters (average cluster population = 209,564)-the Delayed arm. Treatment initiation rates for TB and Anti-Retroviral Therapy (ART) were the primary outcome measures. Secondary outcome measures included testing rates for TB and HIV. We report the results of the comparisons between the Early and Delayed arms over the 23 month trial period. Data were obtained from patient registers. Poisson regression models with robust standard errors were used to express the effectiveness of the intervention as incidence rate ratios (IRR). The Early and Delayed clusters were well matched in terms of baseline monthly mean counts and incidence rate ratios for TB and ART treatment initiation. However there were fewer testing and treatment initiation facilities in the Early clusters (TB treatment n = 2, TB testing n = 7, ART initiation n = 3, HIV testing n = 20) than in the Delayed clusters (TB treatment n = 4, TB testing n = 9, ART initiation n = 6, HIV testing n = 18). Overall there were more HIV testing and treatment centres than TB testing and treatment centres. The IRR was 1.18 (95% CI: 0.903-1.533; p = 0.112) for TB treatment initiation and 1.347 (CI:1.00-1.694; p = 0.049) for ART initiation in the first 12 months and the IRR were 0.552 (95% CI:0

  12. Student Engagement

    DEFF Research Database (Denmark)

    Conduit, Jodie; Karpen, Ingo; Farrelly, Francis

    2017-01-01

    Universities are seeking to actively and strategically manage student engagement through providing opportunities for students to interact and engage with the institution on a range of levels and in different ways. However, this increasingly complex and multi-layered nature of student engagement...... focal objects (or levels) embedded within the university structure; the lecturer, course and the institution itself. Hence, this paper contributes to the literature by providing a multi-layered consideration of student engagement and demonstrating the nested nature of engagement across the broad service...... system (the university), the narrow service system (the course), and the individual dyadic level of engagement (the student-lecturer interaction). These findings could be further considered and empirically tested in other engagement contexts (e.g. employee engagement, customer engagement)....

  13. A community-engaged randomized controlled trial of an integrative intervention with HIV-positive, methamphetamine-using men who have sex with men.

    Science.gov (United States)

    Carrico, Adam W; Jain, Jennifer; Discepola, Michael V; Olem, David; Andrews, Rick; Woods, William J; Neilands, Torsten B; Shoptaw, Steven; Gómez, Walter; Dilworth, Samantha E; Moskowitz, Judith T

    2016-07-30

    Contingency management (CM) is an evidence-based intervention providing tangible rewards as positive reinforcement for abstinence from stimulants such as methamphetamine. Integrative approaches targeting affect regulation could boost the effectiveness of CM in community-based settings and optimize HIV/AIDS prevention efforts. This randomized controlled trial with HIV-positive, methamphetamine-using men who have sex with men (MSM) is examining the efficacy of a 5-session, individually delivered positive affect regulation intervention - Affect Regulation Treatment to Enhance Methamphetamine Intervention Success (ARTEMIS). ARTEMIS is designed to sensitize individuals to non-drug-related sources of reward as well as assist with managing depression and other symptoms of stimulant withdrawal during CM. HIV-positive, methamphetamine-using MSM who are enrolled in a community-based, 12-week CM program are randomized to receive ARTEMIS or an attention-matched control condition. Follow-up assessments are conducted at 3, 6, 12, and 15 months after enrollment in CM. Four peripheral venous blood samples are collected over the 15-month follow-up with specimen banking for planned biomarker sub-studies. The primary outcome is mean HIV viral load. Secondary outcomes include: sustained HIV viral suppression, T-helper cell count, psychological adjustment, stimulant use, and potentially amplified transmission risk behavior. Implementation of this randomized controlled trial highlights the importance of delineating boundaries between research activities and community-based service provision. It also provides insights into best practices for integrating the distinct agendas of academic and community partners in clinical research. This trial is currently enrolling and data collection is anticipated to be completed in September of 2018. This trial was registered on clinicaltrials.gov ( NCT01926184 ) on August 16, 2013.

  14. A community-engaged randomized controlled trial of an integrative intervention with HIV-positive, methamphetamine-using men who have sex with men

    Directory of Open Access Journals (Sweden)

    Adam W. Carrico

    2016-07-01

    Full Text Available Abstract Background Contingency management (CM is an evidence-based intervention providing tangible rewards as positive reinforcement for abstinence from stimulants such as methamphetamine. Integrative approaches targeting affect regulation could boost the effectiveness of CM in community-based settings and optimize HIV/AIDS prevention efforts. Methods/Design This randomized controlled trial with HIV-positive, methamphetamine-using men who have sex with men (MSM is examining the efficacy of a 5-session, individually delivered positive affect regulation intervention – Affect Regulation Treatment to Enhance Methamphetamine Intervention Success (ARTEMIS. ARTEMIS is designed to sensitize individuals to non-drug-related sources of reward as well as assist with managing depression and other symptoms of stimulant withdrawal during CM. HIV-positive, methamphetamine-using MSM who are enrolled in a community-based, 12-week CM program are randomized to receive ARTEMIS or an attention-matched control condition. Follow-up assessments are conducted at 3, 6, 12, and 15 months after enrollment in CM. Four peripheral venous blood samples are collected over the 15-month follow-up with specimen banking for planned biomarker sub-studies. The primary outcome is mean HIV viral load. Secondary outcomes include: sustained HIV viral suppression, T-helper cell count, psychological adjustment, stimulant use, and potentially amplified transmission risk behavior. Discussion Implementation of this randomized controlled trial highlights the importance of delineating boundaries between research activities and community-based service provision. It also provides insights into best practices for integrating the distinct agendas of academic and community partners in clinical research. This trial is currently enrolling and data collection is anticipated to be completed in September of 2018. Trial registration This trial was registered on clinicaltrials.gov ( NCT01926184 on

  15. HIV-1 envelope sequence-based diversity measures for identifying recent infections.

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    Alexis Kafando

    Full Text Available Identifying recent HIV-1 infections is crucial for monitoring HIV-1 incidence and optimizing public health prevention efforts. To identify recent HIV-1 infections, we evaluated and compared the performance of 4 sequence-based diversity measures including percent diversity, percent complexity, Shannon entropy and number of haplotypes targeting 13 genetic segments within the env gene of HIV-1. A total of 597 diagnostic samples obtained in 2013 and 2015 from recently and chronically HIV-1 infected individuals were selected. From the selected samples, 249 (134 from recent versus 115 from chronic infections env coding regions, including V1-C5 of gp120 and the gp41 ectodomain of HIV-1, were successfully amplified and sequenced by next generation sequencing (NGS using the Illumina MiSeq platform. The ability of the four sequence-based diversity measures to correctly identify recent HIV infections was evaluated using the frequency distribution curves, median and interquartile range and area under the curve (AUC of the receiver operating characteristic (ROC. Comparing the median and interquartile range and evaluating the frequency distribution curves associated with the 4 sequence-based diversity measures, we observed that the percent diversity, number of haplotypes and Shannon entropy demonstrated significant potential to discriminate recent from chronic infections (p<0.0001. Using the AUC of ROC analysis, only the Shannon entropy measure within three HIV-1 env segments could accurately identify recent infections at a satisfactory level. The env segments were gp120 C2_1 (AUC = 0.806, gp120 C2_3 (AUC = 0.805 and gp120 V3 (AUC = 0.812. Our results clearly indicate that the Shannon entropy measure represents a useful tool for predicting HIV-1 infection recency.

  16. Occurrence of an HIV-1 gp160 endoproteolytic activity in low-density vesicles and evidence for a distinct density distribution from endogenously expressed furin and PC7/LPC convertases.

    Science.gov (United States)

    Wouters, S; Decroly, E; Vandenbranden, M; Shober, D; Fuchs, R; Morel, V; Leruth, M; Seidah, N G; Courtoy, P J; Ruysschaert, J M

    1999-07-30

    Human immunodeficiency virus (HIV) glycoprotein (gp) 160 processing by host cell proteinases is an essential step for viral fusion and infectivity. We have identified a rat liver subcellular fraction which specifically processes gp160 into gp120 and gp41. Using equilibration of microsomes in sucrose gradients, the gp160 cleavage activity was associated with particles equilibrating at low densities, well-separated from the endoplasmic reticulum, cis-Golgi network, Golgi stacks, lysosomes and plasma membrane. Its density distribution was compatible with light secretory vesicles derived from the trans-Golgi network (TGN) or to endosomes, but association with endosomes was not supported by free flow electrophoresis. Although furin and pro-protein convertase (PC) 7/LPC have been proposed as the major gp160 processing convertases, the rat liver microsomal gp160 processing activity was essentially resolved from furin and only partially overlapped PC7/LPC. These data suggest that proteinase(s) other than furin and PC7/LPC, presumably located in TGN-derived vesicles, may participate in the gp160 processing into gp120 and gp41.

  17. Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity

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    Claiborne Daniel T

    2011-05-01

    Full Text Available Abstract Background The gp41 component of the Human Immunodeficiency Virus (HIV envelope glycoprotein (Env contains a long cytoplasmic domain (CD with multiple highly conserved tyrosine (Y and dileucine (LL motifs. Studies suggest that the motifs distal to major endocytosis motif (Y712HRL, located at residues 712-715 of Env, may contribute to Env functionality in the viral life cycle. In order to examine the biological contribution of these motifs in the biosynthesis, transport, and function of Env, we constructed two panels of mutants in which the conserved Y- and LL-motifs were sequentially substituted by alternative residues, either in the presence or absence of Y712. Additional mutants targeting individual motifs were then constructed. Results All mutant Envs, when expressed in the absence of other viral proteins, maintained at least WT levels of Env surface staining by multiple antibodies. The Y712 mutation (Y712C contributed to at least a 4-fold increase in surface expression for all mutants containing this change. Sequential mutagenesis of the Y- and LL-motifs resulted in a generally progressive decrease in Env fusogenicity. However, additive mutation of dileucine and tyrosine motifs beyond the tyrosine at residue 768 resulted in the most dramatic effects on Env incorporation into virions, viral infectivity, and virus fusion with target cells. Conclusions From the studies reported here, we show that mutations of the Y- and LL-motifs, which effectively eliminate the amphipathic nature of the lytic peptide 2 (LLP2 domain or disrupt YW and LL motifs in a region spanning residues 795-803 (YWWNLLQYW, just C-terminal of LLP2, can dramatically interfere with biological functions of HIV-1 Env and abrogate virus replication. Because these mutant proteins are expressed at the cell surface, we conclude that tyrosine and di-leucine residues within the cytoplasmic domain of gp41 play critical roles in HIV-1 replication that are distinct from that of

  18. Prediction of exposed domains of envelope glycoprotein in Indian HIV-1 isolates and experimental confirmation of their immunogenicity in humans

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    Mohabatkar H.

    2004-01-01

    Full Text Available We describe the impact of subtype differences on the seroreactivity of linear antigenic epitopes in envelope glycoprotein of HIV-1 isolates from different geographical locations. By computer analysis, we predicted potential antigenic sites of envelope glycoprotein (gp120 and gp4l of this virus. For this purpose, after fetching sequences of proteins of interest from data banks, values of hydrophilicity, flexibility, accessibility, inverted hydrophobicity, and secondary structure were considered. We identified several potential antigenic epitopes in a B subtype strain of envelope glycoprotein of HIV-1 (IIIB. Solid- phase peptide synthesis methods of Merrifield and Fmoc chemistry were used for synthesizing peptides. These synthetic peptides corresponded mainly to the C2, V3 and CD4 binding sites of gp120 and some parts of the ectodomain of gp41. The reactivity of these peptides was tested by ELISA against different HIV-1-positive sera from different locations in India. For two of these predicted epitopes, the corresponding Indian consensus sequences (LAIERYLKQQLLGWG and DIIGDIRQAHCNISEDKWNET (subtype C were also synthesized and their reactivity was tested by ELISA. These peptides also distinguished HIV-1-positive sera of Indians with C subtype infections from sera from HIV-negative subjects.

  19. Immediate Blood Draw for CD4+ Cell Count Is Associated with Linkage to Care in Durban, South Africa: Findings from Pathways to Engagement in HIV Care.

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    Susie Hoffman

    Full Text Available Timely linkage to care by newly-diagnosed HIV+ individuals remains a significant challenge to achieving UNAIDS 90-90-90 goals. Current World Health Organization (WHO guidelines recommend initiating anti-retroviral treatment (ART regardless of CD4+ count, with priority given to those with CD4+ <350 cells/μl. We evaluated the impact of not having a day-of-diagnosis CD4+ count blood draw, as recommended by South African guidelines, on time to linkage, using data from a prospective cohort study.Individuals (N = 2773 were interviewed prior to HIV counseling and testing at three public sector primary care clinics in the greater Durban area; 785 were newly-diagnosed and eligible for the cohort study; 459 (58.5% joined and were followed for eight months with three structured assessments. Linkage to care, defined as returning to clinic for CD4+ count results, and day-of-diagnosis blood draw were self-reported.Overall, 72.5% did not have a day-of-diagnosis CD4+ count blood draw, and 19.2% of these never returned. Compared with a day-of-diagnosis blood draw, the adjusted hazard ratio of linkage (AHRlinkage associated with not having day-of-diagnosis blood draw was 0.66 (95%CI: 0.51, 0.85. By 4 months, 54.8% of those without day-of-diagnosis blood draw vs. 75.2% with one were linked to care (chi-squared p = 0.004. Of those who deferred blood draw, 48.3% cited clinic-related and 51.7% cited personal reasons. AHRlinkage was 0.60 (95%CI: 0.44, 0.82 for clinic-related and 0.53 (95%CI: 0.38, 0.75 for personal reasons relative to having day-of-diagnosis blood draw.Newly-diagnosed HIV+ individuals who did not undergo CD4+ count blood draw on the day they were diagnosed-regardless of the reason for deferring-had delayed linkage to care relative to those with same-day blood draw. To enhance prompt linkage to care even when test and treat protocols are implemented, all diagnostic testing required before ART initiation should be performed on the same day as HIV

  20. Synthetic peptides of hepatitis G virus (GBV-C/HGV) in the selection of putative peptide inhibitors of the HIV-1 fusion peptide.

    Science.gov (United States)

    Herrera, Elena; Gomara, Maria J; Mazzini, Stefania; Ragg, Enzio; Haro, Isabel

    2009-05-21

    The GB virus C or hepatitis G virus (GBV-C/HGV) is a single-stranded positive sense RNA virus that belongs to the Flaviviridae family. Recent years have seen the publication of numerous works in which coinfection with GBV-C/HGV and HIV has been associated with slower progression of the illness and a higher survival rate of patients once AIDS has developed. The mechanism by which the GBV-C/HGV virus has a "protective effect" in patients with HIV has still not been defined. Study of the interaction of the GBV-C/HGV and HIV viruses could lead to the development of new therapeutic agents for the treatment of AIDS. Given that the mechanism responsible for the beneficial effect exercised by the GBV-C/HGV virus in the course of HIV infection has not been defined, the present work is intended as a study of the structure and interactions between the fusion peptide of HIV-1, gp41(1-23), and synthetic peptide sequences of the E2 envelope protein of GBV-C/HGV using biophysical techniques. Our results highlight that the E2(269-286) sequence interacts with the target fusion peptide of HIV-1 and modifies its conformation.

  1. Transplanting supersites of HIV-1 vulnerability.

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    Tongqing Zhou

    Full Text Available One strategy for isolating or eliciting antibodies against a specific target region on the envelope glycoprotein trimer (Env of the human immunodeficiency virus type 1 (HIV-1 involves the creation of site transplants, which present the target region on a heterologous protein scaffold with preserved antibody-binding properties. If the target region is a supersite of HIV-1 vulnerability, recognized by a collection of broadly neutralizing antibodies, this strategy affords the creation of "supersite transplants", capable of binding (and potentially eliciting antibodies similar to the template collection of effective antibodies. Here we transplant three supersites of HIV-1 vulnerability, each targeted by effective neutralizing antibodies from multiple donors. To implement our strategy, we chose a single representative antibody against each of the target supersites: antibody 10E8, which recognizes the membrane-proximal external region (MPER on the HIV-1 gp41 glycoprotein; antibody PG9, which recognizes variable regions one and two (V1V2 on the HIV-1 gp120 glycoprotein; and antibody PGT128 which recognizes a glycopeptide supersite in variable region 3 (glycan V3 on gp120. We used a structural alignment algorithm to identify suitable acceptor proteins, and then designed, expressed, and tested antigenically over 100-supersite transplants in a 96-well microtiter-plate format. The majority of the supersite transplants failed to maintain the antigenic properties of their respective template supersite. However, seven of the glycan V3-supersite transplants exhibited nanomolar affinity to effective neutralizing antibodies from at least three donors and recapitulated the mannose9-N-linked glycan requirement of the template supersite. The binding of these transplants could be further enhanced by placement into self-assembling nanoparticles. Essential elements of the glycan V3 supersite, embodied by as few as 3 N-linked glycans and ∼ 25 Env residues, can be

  2. Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition.

    Science.gov (United States)

    Ding, Xiaohui; Zhang, Xiujuan; Chong, Huihui; Zhu, Yuanmei; Wei, Huamian; Wu, Xiyuan; He, Jinsheng; Wang, Xinquan; He, Yuxian

    2017-09-15

    The peptide drug enfuvirtide (T20) is the only viral fusion inhibitor used in combination therapy for HIV-1 infection, but it has relatively low antiviral activity and easily induces drug resistance. Emerging studies demonstrate that lipopeptide-based fusion inhibitors, such as LP-11 and LP-19, which mainly target the gp41 pocket site, have greatly improved antiviral potency and in vivo stability. In this study, we focused on developing a T20-based lipopeptide inhibitor that lacks pocket-binding sequence and targets a different site. First, the C-terminal tryptophan-rich motif (TRM) of T20 was verified to be essential for its target binding and inhibition; then, a novel lipopeptide, termed LP-40, was created by replacing the TRM with a fatty acid group. LP-40 showed markedly enhanced binding affinity for the target site and dramatically increased inhibitory activity on HIV-1 membrane fusion, entry, and infection. Unlike LP-11 and LP-19, which required a flexible linker between the peptide sequence and the lipid moiety, addition of a linker to LP-40 sharply reduced its potency, implying different binding modes with the extended N-terminal helices of gp41. Also, interestingly, LP-40 showed more potent activity than LP-11 in inhibiting HIV-1 Env-mediated cell-cell fusion while it was less active than LP-11 in inhibiting pseudovirus entry, and the two inhibitors displayed synergistic antiviral effects. The crystal structure of LP-40 in complex with a target peptide revealed their key binding residues and motifs. Combined, our studies have not only provided a potent HIV-1 fusion inhibitor, but also revealed new insights into the mechanisms of viral inhibition. IMPORTANCE T20 is the only membrane fusion inhibitor available for treatment of viral infection; however, T20 requires high doses and has a low genetic barrier for resistance, and its inhibitory mechanism and structural basis remain unclear. Here, we report the design of LP-40, a T20-based lipopeptide inhibitor

  3. Micelle-induced curvature in a water-insoluble HIV-1 Env peptide revealed by NMR dipolar coupling measurement in stretched polyacrylamide gel.

    Science.gov (United States)

    Chou, James J; Kaufman, Joshua D; Stahl, Stephen J; Wingfield, Paul T; Bax, Ad

    2002-03-20

    The structure of a water-insoluble fragment encompassing residues 282-304 of the HIV envelope protein gp41 is studied when solubilized by dihexanoyl phosphatidylcholine (DHPC) and by small bicelles, consisting of a 4:1 molar ratio of DHPC and dimyristoyl phosphatidylcholine (DMPC). Weak alignment with the magnetic field was accomplished in a stretched polyacrylamide gel, permitting measurement of one-bond (1)H-(15)N, (13)Ca-(13)C', and (13)C'-(15)N dipolar couplings, which formed the basis for determining the peptide structure. In both detergent systems, the peptide adopts an alpha-helical conformation from residue 4 through 18. In the presence of the DHPC micelles the helix is strongly curved towards the hydrophobic surface, whereas in the presence of bicelles a much weaker curvature in the opposite direction is observed.

  4. Preinfection human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes failed to prevent HIV type 1 infection from strains genetically unrelated to viruses in long-term exposed partners.

    Science.gov (United States)

    Liu, Yi; Woodward, Amanda; Zhu, Haiying; Andrus, Thomas; McNevin, John; Lee, Jean; Mullins, James I; Corey, Lawrence; McElrath, M Juliana; Zhu, Tuofu

    2009-10-01

    Understanding the mechanisms underlying potential altered susceptibility to human immunodeficiency virus type 1 (HIV-1) infection in highly exposed seronegative (ES) individuals and the later clinical consequences of breakthrough infection can provide insight into strategies to control HIV-1 with an effective vaccine. From our Seattle ES cohort, we identified one individual (LSC63) who seroconverted after over 2 years of repeated unprotected sexual contact with his HIV-1-infected partner (P63) and other sexual partners of unknown HIV-1 serostatus. The HIV-1 variants infecting LSC63 were genetically unrelated to those sequenced from P63. This may not be surprising, since viral load measurements in P63 were repeatedly below 50 copies/ml, making him an unlikely transmitter. However, broad HIV-1-specific cytotoxic T-lymphocyte (CTL) responses were detected in LSC63 before seroconversion. Compared to those detected after seroconversion, these responses were of lower magnitude and half of them targeted different regions of the viral proteome. Strong HLA-B27-restricted CTLs, which have been associated with disease control, were detected in LSC63 after but not before seroconversion. Furthermore, for the majority of the protein-coding regions of the HIV-1 variants in LSC63 (except gp41, nef, and the 3' half of pol), the genetic distances between the infecting viruses and the viruses to which he was exposed through P63 (termed the exposed virus) were comparable to the distances between random subtype B HIV-1 sequences and the exposed viruses. These results suggest that broad preinfection immune responses were not able to prevent the acquisition of HIV-1 infection in LSC63, even though the infecting viruses were not particularly distant from the viruses that may have elicited these responses.

  5. Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160.

    Science.gov (United States)

    Polpitiya Arachchige, Sachith; Henke, Wyatt; Pramanik, Ankita; Kalamvoki, Maria; Stephens, Edward B

    2018-01-15

    Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways.IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4+ T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell. Copyright © 2018 American Society for Microbiology.

  6. [Comparative study of the placenta from HIV+ mothers. Ultrastructural analysis].

    Science.gov (United States)

    Villegas-Castrejon, H; Paredes-Vivas, Y; Flores-Rivera, E; Gorbea-Robles, M C; Arredondo-Garcia, J L

    1996-04-01

    Perinatal vertical transmission has increased in all the world; it is considered that at the present time there are about one million of children with HIV. Variation goes from 12 to 40%, at different countries. During the last years antiretroviral drugs as AZT, ddI and others have been used to diminish the virus passage via transplacentary. Eighteen placentaes from HIV seropositive women, three corresponded to first trimester, and 15 to the third trimester of gestation; in four cases they were treated with AZT in weeks fourteen (two patients), 26 and 35 of gestation; and one patient received AZT and ddI at week 28. Control group was with ten normal placentaes. Ultraestructural analysis and immuno-peroxidase and immuno-oro with antibody anti gp 41, were done. Ultraestructurally there were different localizations of HIV virus, at sincitiotrophoblast, decidual cells and umbilical vessels (six cases). In 13 cases there was hyperplasia and hypertrophy of macrophages containing a great amount of lysosomes. In one case, where a girl was seropositive many viriones HIV, were identified in macrophages. With immuno-oro viral proteins were seen in cytoplasm an plasmatic membrane, in endothelium of fetal capillars and trophoblast. With immunoperoxidase, four cases were positive. Placentaes with antiretroviral treatment since week 14, trophoblast was more dense by philaments increment. Placentaes with treatment during the third trimester, showed normal morphology with slight increase of philaments. In the cases treated with AZT and ddI, there were not macrophages hyperplasia and hypertrophy, nor viral particles. It is concluded that in seropositive mothers without treatment, the virus may be present in any part of chorionic villi, and in patients with treatment, virus is not identified, but a viral proteins synthesis.

  7. Detailed topology mapping reveals substantial exposure of the "cytoplasmic" C-terminal tail (CTT sequences in HIV-1 Env proteins at the cell surface.

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    Jonathan D Steckbeck

    Full Text Available Substantial controversy surrounds the membrane topology of the HIV-1 gp41 C-terminal tail (CTT. While few studies have been designed to directly address the topology of the CTT, results from envelope (Env protein trafficking studies suggest that the CTT sequence is cytoplasmically localized, as interactions with intracellular binding partners are required for proper Env targeting. However, previous studies from our lab demonstrate the exposure of a short CTT sequence, the Kennedy epitope, at the plasma membrane of intact Env-expressing cells, the exposure of which is not observed on viral particles. To address the topology of the entire CTT sequence, we serially replaced CTT sequences with a VSV-G epitope tag sequence and examined reactivity of cell- and virion-surface Env to an anti-VSV-G monoclonal antibody. Our results demonstrate that the majority of the CTT sequence is accessible to antibody binding on the surface of Env expressing cells, and that the CTT-exposed Env constitutes 20-50% of the cell-surface Env. Cell surface CTT exposure was also apparent in virus-infected cells. Passive transfer of Env through cell culture media to Env negative (non-transfected cells was not responsible for the apparent cell surface CTT exposure. In contrast to the cell surface results, CTT-exposed Env was not detected on infectious pseudoviral particles containing VSV-G-substituted Env. Finally, a monoclonal antibody directed to the Kennedy epitope neutralized virus in a temperature-dependent manner in a post-attachment neutralization assay. Collectively, these results suggest that the membrane topology of the HIV gp41 CTT is more complex than the widely accepted intracytoplasmic model.

  8. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies.

    Science.gov (United States)

    Sanders, Rogier W; Derking, Ronald; Cupo, Albert; Julien, Jean-Philippe; Yasmeen, Anila; de Val, Natalia; Kim, Helen J; Blattner, Claudia; de la Peña, Alba Torrents; Korzun, Jacob; Golabek, Michael; de Los Reyes, Kevin; Ketas, Thomas J; van Gils, Marit J; King, C Richter; Wilson, Ian A; Ward, Andrew B; Klasse, P J; Moore, John P

    2013-09-01

    A desirable but as yet unachieved property of a human immunodeficiency virus type 1 (HIV-1) vaccine candidate is the ability to induce broadly neutralizing antibodies (bNAbs). One approach to the problem is to create trimeric mimics of the native envelope glycoprotein (Env) spike that expose as many bNAb epitopes as possible, while occluding those for non-neutralizing antibodies (non-NAbs). Here, we describe the design and properties of soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A transmitted/founder strain, BG505. These trimers are highly stable, more so even than the corresponding gp120 monomer, as judged by differential scanning calorimetry. They are also homogenous and closely resemble native virus spikes when visualized by negative stain electron microscopy (EM). We used several techniques, including ELISA and surface plasmon resonance (SPR), to determine the relationship between the ability of monoclonal antibodies (MAbs) to bind the soluble trimers and neutralize the corresponding virus. In general, the concordance was excellent, in that virtually all bNAbs against multiple neutralizing epitopes on HIV-1 Env were highly reactive with the BG505 SOSIP.664 gp140 trimers, including quaternary epitopes (CH01, PG9, PG16 and PGT145). Conversely, non-NAbs to the CD4-binding site, CD4-induced epitopes or gp41ECTO did not react with the trimers, even when their epitopes were present on simpler forms of Env (e.g. gp120 monomers or dissociated gp41 subunits). Three non-neutralizing MAbs to V3 epitopes did, however, react strongly with the trimers but only by ELISA, and not at all by SPR and to only a limited extent by EM. These new soluble trimers are useful for structural studies and are being assessed for their performance as immunogens.

  9. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Rogier W Sanders

    2013-09-01

    Full Text Available A desirable but as yet unachieved property of a human immunodeficiency virus type 1 (HIV-1 vaccine candidate is the ability to induce broadly neutralizing antibodies (bNAbs. One approach to the problem is to create trimeric mimics of the native envelope glycoprotein (Env spike that expose as many bNAb epitopes as possible, while occluding those for non-neutralizing antibodies (non-NAbs. Here, we describe the design and properties of soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A transmitted/founder strain, BG505. These trimers are highly stable, more so even than the corresponding gp120 monomer, as judged by differential scanning calorimetry. They are also homogenous and closely resemble native virus spikes when visualized by negative stain electron microscopy (EM. We used several techniques, including ELISA and surface plasmon resonance (SPR, to determine the relationship between the ability of monoclonal antibodies (MAbs to bind the soluble trimers and neutralize the corresponding virus. In general, the concordance was excellent, in that virtually all bNAbs against multiple neutralizing epitopes on HIV-1 Env were highly reactive with the BG505 SOSIP.664 gp140 trimers, including quaternary epitopes (CH01, PG9, PG16 and PGT145. Conversely, non-NAbs to the CD4-binding site, CD4-induced epitopes or gp41ECTO did not react with the trimers, even when their epitopes were present on simpler forms of Env (e.g. gp120 monomers or dissociated gp41 subunits. Three non-neutralizing MAbs to V3 epitopes did, however, react strongly with the trimers but only by ELISA, and not at all by SPR and to only a limited extent by EM. These new soluble trimers are useful for structural studies and are being assessed for their performance as immunogens.

  10. Poor clinical outcomes for HIV infected children on antiretroviral therapy in rural Mozambique: need for program quality improvement and community engagement.

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    Sten H Vermund

    Full Text Available Residents of Zambézia Province, Mozambique live from rural subsistence farming and fishing. The 2009 provincial HIV prevalence for adults 15-49 years was 12.6%, higher among women (15.3% than men (8.9%. We reviewed clinical data to assess outcomes for HIV-infected children on combination antiretroviral therapy (cART in a highly resource-limited setting.We studied rates of 2-year mortality and loss to follow-up (LTFU for children 60 days following last-scheduled medication pickup. Kaplan-Meier estimates to compute mortality assumed non-informative censoring. Cumulative LTFU incidence calculations treated death as a competing risk.Of 753 children, 29.0% (95% CI: 24.5, 33.2 were confirmed dead by 2 years and 39.0% (95% CI: 34.8, 42.9 were LTFU with unknown clinical outcomes. The cohort mortality rate was 8.4% (95% CI: 6.3, 10.4 after 90 days on cART and 19.2% (95% CI: 16.0, 22.3 after 365 days. Higher hemoglobin at cART initiation was associated with being alive and on cART at 2 years (alive: 9.3 g/dL vs. dead or LTFU: 8.3-8.4 g/dL, p<0.01. Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes Treatment was initiated late (WHO stage III/IV among 48% of the children with WHO stage recorded in their records. Marked heterogeneity in outcomes by district was noted (p<0.001.We found poor clinical and programmatic outcomes among children taking cART in rural Mozambique. Expanded testing, early infant diagnosis, counseling/support services, case finding, and outreach are insufficiently implemented. Our quality improvement efforts seek to better link pregnancy and HIV services, expand coverage and timeliness of infant diagnosis and treatment, and increase follow-up and adherence.

  11. Interactions between HIV-1 Neutralizing Antibodies and Model Lipid Membranes imaged with AFM

    Science.gov (United States)

    Zauscher, Stefan; Hardy, Gregory; Alam, Munir; Shapter, Joseph

    2012-02-01

    Lipid membrane interactions with rare, broadly neutralizing antibodies (NAbs), 2F5 and 4E10, play a critical role in HIV-1 neutralization. Our research is motivated by recent immunization studies that have shown that induction of antibodies that avidly bind the gp41-MPER antigen is not sufficient for neutralization. Rather, it is required that antigen designs induce polyreactive antibodies that recognize MPER antigens as well as the viral lipid membrane. However, the mechanistic details of how membrane properties influence NAb-lipid and NAb-antigen interactions remain unknown. Furthermore, it is well established that the native viral membrane is heterogeneous, representing a mosaic of lipid rafts and protein clustering. However, the size, physical properties, and dynamics of these regions are poorly characterized and their potential roles in HIV-1 neutralization are also unknown. To understand how membrane properties contribute to 2F5/4E10 membrane interactions, we have engineered biomimetic supported lipid bilayers (SLBs) and use atomic force microscopy to visualize membrane domains, antigen clustering, and antibody-membrane interactions at sub-nanometer z-resolution. Our results show that localized binding of HIV-1 antigens and NAbs occur preferentially with the most fluid membrane domain. This supports the theory that NAbs may interact with regions of low lateral lipid forces that allow antibody insertion into the bilayer.

  12. HIV care and treatment experiences among female sex workers ...

    African Journals Online (AJOL)

    Female sex workers (FSW) living with HIV in sub-Saharan Africa have poor engagement to HIV care and treatment. Understanding the HIV care and treatment engagement experiences of FSW has important implications for interventions to enhance care and treatment outcomes. We conducted a systematic review to ...

  13. A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-06-01

    Full Text Available Abstract Background The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV, however, possesses several mechanisms to evade complement-mediated lysis (CoML and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. Presentation of the hypothesis Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d-Fc, can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. Testing the hypothesis Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d-Fc proteins. As a control group, viruses

  14. Different pattern of immunoglobulin gene usage by HIV-1 compared to non-HIV-1 antibodies derived from the same infected subject.

    Science.gov (United States)

    Li, Liuzhe; Wang, Xiao-Hong; Banerjee, Sagarika; Volsky, Barbara; Williams, Constance; Virland, Diana; Nadas, Arthur; Seaman, Michael S; Chen, Xuemin; Spearman, Paul; Zolla-Pazner, Susan; Gorny, Miroslaw K

    2012-01-01

    A biased usage of immunoglobulin (Ig) genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs) resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP) expressing HIV-1 envelope (Env) proteins of JRFL and BaL and control VLPs (without Env) were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis.

  15. Different pattern of immunoglobulin gene usage by HIV-1 compared to non-HIV-1 antibodies derived from the same infected subject.

    Directory of Open Access Journals (Sweden)

    Liuzhe Li

    Full Text Available A biased usage of immunoglobulin (Ig genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP expressing HIV-1 envelope (Env proteins of JRFL and BaL and control VLPs (without Env were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis.

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... risk of contracting HIV, and using drugs and alcohol can increase the chances of unsafe behavior by altering judgment and ... Drug Facts: Drug Use and Viral Infections : Describes how people who engage ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug misuse are among the main ... lead people to engage in impulsive and unsafe behaviors. Injection drug use. People typically associate drug misuse ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... teen years are when young people engage in risk-taking and sensation-seeking behaviors. Unsafe sexual practices increase a person's risk of contracting HIV, and using drugs and alcohol ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... disease and permanent liver damage. Poor judgment and risky behavior. Drug abuse by any route (not just injection) ... the influence of drugs and alcohol engaged in risky sexual behavior that resulted in HIV infection. Watch the "After ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug abuse are among the main ... lead people to engage in impulsive and unsafe behaviors. Injection drug use. People typically associate drug abuse ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... brain cells 1 . Drug abuse treatment. Since the late 1980s, research has shown that treating drug abuse ... risk for contracting HIV. In general, middle and late teen years are when young people engage in ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... for contracting HIV. In general, middle and late teen years are when young people engage in risk-taking and sensation-seeking behaviors. Unsafe sexual practices increase a person's risk of ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Pathol. 2010. 177(1):355-361. How are Teens Affected? Young people are at risk for contracting HIV. In general, middle and late teen years are when young people engage in risk- ...

  4. Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures.

    Directory of Open Access Journals (Sweden)

    Isabella Bon

    Full Text Available Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1 strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs and, importantly, the surface plasmon resonance (SPR assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1.

  5. Citizenship status and engagement in HIV care: an observational cohort study to assess the association between reporting a national ID number and retention in public-sector HIV care in Johannesburg, South Africa.

    Science.gov (United States)

    Shearer, Kate; Clouse, Kate; Meyer-Rath, Gesine; MacLeod, William; Maskew, Mhairi; Sanne, Ian; Long, Lawrence; Fox, Matthew P

    2017-01-24

    In many resource-limited settings, people from rural areas migrate to urban hubs in search of work. Thus, urban public-sector HIV clinics in South Africa (SA) often cater to both local residents and patients from other provinces and/or countries. The objective of this analysis was to compare programmatic treatment outcomes by citizenship status in an urban clinic in SA. An urban public-sector HIV treatment facility in Johannesburg, SA. We included all antiretroviral therapy (ART)-naïve, non-pregnant patients who initiated standard first-line treatment from January 2008 to December 2013. 12 219 patients were included and 59.5% were women. Patients were followed from ART initiation until death, transfer, loss to follow-up (LTF), or data set closure. We describe attrition (mortality and LTF) stratified by SA citizenship status (confirmed SA citizens (with national ID number), unconfirmed SA citizens (no ID), and foreign nationals) and model the risk of attrition using Cox proportional hazards regression. 70% of included patients were confirmed SA citizens, 19% were unconfirmed SA citizens, and 11% were foreign nationals. Unconfirmed SA citizens were far more likely to die or become LTF than other patients. A similar proportion of foreign nationals (18.2%) and confirmed SA citizens (17.7%) had left care at 1 year compared with 47.0% of unconfirmed SA citizens (adjusted hazard ratio (aHR) unconfirmed SA vs confirmed SA: 2.68; 95% CI 2.42 to 2.97). By the end of follow-up, 75.5% of unconfirmed SA citizens had left care, approximately twice that of any other group. Unconfirmed SA citizens were more likely to drop out of care after ART initiation than other patients. Further research is needed to determine whether this observed attrition is representative of migration and/or self-transfer to another HIV clinic as such high rates of attrition pose challenges for the success of the national ART programme. Published by the BMJ Publishing Group Limited. For permission to

  6. Situating Engagement

    DEFF Research Database (Denmark)

    Korn, Matthias

    everyday lives and the spaces we inhabit. Where email and the telephone have broken down barriers of geography, the relationship of technology with physical locations in people’s lives strengthens. From Occupy to the London riots and the Arab Spring, situated technologies offer new ways through which we......’ civic engagement activities in those spatial contexts that are at stake in land use planning. This approach enables engagement activities to be better integrated with people’s everyday lived experiences through connecting to the places that are personally meaningful and relevant to them. A ’research...... a plethora of different means for citizens to engage with planning issues within a plethora of different contexts and situations. The dissertation makes contributions of two kinds. Conceptually, it offers a richer understanding of what is implicated in the design of technologies for situated engagement...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... public service ads (PSA) where an HIV-positive teenager recounts the night she went to a party and under the influence of drugs and alcohol engaged in risky sexual behavior that resulted in HIV infection. Watch the "After ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... who engage in drug use or high-risk behaviors associated with drug use also put themselves at risk for contracting or transmitting HIV/AIDS or other infectious diseases. Research Reports: HIV/AIDS : Explores the link between drug ...

  9. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

    Science.gov (United States)

    McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

    2016-01-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  10. HIV Transmission

    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 | ... on HIV Syndicated Content Website Feedback HIV/AIDS HIV Transmission Language: English (US) Español (Spanish) Recommend on ...

  11. HIV and reproductive healthcare in pregnant and postpartum HIV-infected women: adapting successful strategies.

    Science.gov (United States)

    Rimawi, Bassam H; Smith, Somer L; Badell, Martina L; Zahedi-Spung, Leilah D; Sheth, Anandi N; Haddad, Lisa; Chakraborty, Rana

    2016-08-01

    Linkage and retention in care for many HIV-infected women in the postpartum period is suboptimal, which compromises long-term virologic suppression and the HIV Care Continuum. Efforts are needed to improve individual outcomes by addressing transitions in care. We summarize some successful strategies to engage and retain HIV-infected women in care during the postpartum period.

  12. Targeting cell surface HIV-1 Env protein to suppress infectious virus formation

    Science.gov (United States)

    Bastian, Arangassery Rosemary; Ang, Charles G.; Kamanna, Kantharaju; Shaheen, Farida; Huang, Yu-Hung; McFadden, Karyn; Duffy, Caitlin; Bailey, Lauren D.; Sundaram, Ramalingam Venkat Kalyana; Chaiken, Irwin

    2017-01-01

    HIV-1 Env protein is essential for host cell entry, and targeting Env remains an important antiretroviral strategy. We previously found that a peptide triazole thiol KR13 and its gold nanoparticle conjugate AuNP-KR13 directly and irreversibly inactivate the virus by targeting the Env protein, leading to virus gp120 shedding, membrane disruption and p24 capsid protein release. Here, we examined the consequences of targeting cell-surface Env with the virus inactivators. We found that both agents led to formation of non-infectious virus from transiently transfected 293T cells. The budded non-infectious viruses lacked Env gp120 but contained gp41. Importantly, budded virions also retained the capsid protein p24, in stark contrast to p24 leakage from viruses directly treated by these agents and arguing that the agents led to deformed viruses by transforming the cells at a stage before virus budding. We found that the Env inactivators caused gp120 shedding from the transiently transfected 293T cells as well as non-producer CHO-K1-gp160 cells. Additionally, AuNP-KR13 was cytotoxic against the virus-producing 293T and CHO-K1-gp160 cells, but not untransfected 293T or unmodified CHO-K1 cells. The results obtained reinforce the argument that cell-surface HIV-1 Env is metastable, as on virus particles, and provides a conformationally vulnerable target for virus suppression and infectious cell inactivation. PMID:28390972

  13. Engaging Siblingships

    DEFF Research Database (Denmark)

    Gulløv, Eva; Palludan, Charlotte; Winther, Ida Wentzel

    2015-01-01

    and young people in contemporary Denmark engage emotionally in sibling relationships. It emerges that siblingships inevitably involve frictions in various forms. In the article, we analyse the impact frictions have on social relations and discuss how such dynamics in sibling relationships both reflect...... and influence family constitutions and dynamics....

  14. Enfuvirtide cerebrospinal fluid (CSF) pharmacokinetics and potential use in defining CSF HIV-1 origin.

    Science.gov (United States)

    Price, Richard W; Parham, Robin; Kroll, Jing Lu; Wring, Stephen A; Baker, Brian; Sailstad, Jeff; Hoh, Rebecca; Liegler, Teri; Spudich, Serena; Kuritzkes, Daniel R; Deeks, Steven G

    2008-01-01

    Enfuvirtide is a potent inhibitor of systemic HIV-1 replication, but its penetration into the human central nervous system (CNS) has not been analysed. Here, we define cerebrospinal fluid (CSF) enfuvirtide pharmacokinetics and present a case illustrating the use of enfuvirtide as a probe to trace the origins of CSF HIV-1 quasispecies. Enfuvirtide CSF pharmacokinetics were assessed in 18 CSF and plasma sample pairs from four HIV-1-infected individuals. Enfuvirtide levels were measured by liquid chromatography tandem mass spectrometry using known standards and controls that included spiked CSF samples from untreated, HIV-negative individuals. A segment of the gp41 coding region encompassing the heptad repeat HR-1 and HR-2 domains was amplified from selected CSF and plasma samples and independent clones sequenced to assess resistance-associated mutations. CSF and plasma samples obtained between 2 and 20 h after enfuvirtide injection showed plasma concentrations similar to previous reports (mean 3.687 SD +/- 1.828 mg/ml) with prolonged decay. By contrast, enfuvirtide in all CSF samples was below the assay detection limit of 0.025 mg/ml. In one individual, who developed a transient increase in CSF HIV-1 RNA, seven of seven CSF and plasma clones had identical enfuvirtide resistance-associated V38A mutations, suggesting that the CSF quasispecies derived from that of blood. Enfuvirtide penetration into CSF is negligible; thus, in clinical settings, where direct CNS drug exposure is crucial, this drug Is not likely to directly contribute to the local therapeutic effect. Enfuvirtide can be used as a tool to dissect the origin of the CNS virus.

  15. The role of jails in engaging PLWHA in care: from jail to community.

    Science.gov (United States)

    Rapp, Richard C; Ciomcia, Rachel; Zaller, Nick; Draine, Jeff; Ferguson, Ann; Cagey, Robin

    2013-10-01

    HIV testing in jails has provided public health officials with the opportunity to not only identify new cases of HIV but to also reestablish contact with previously diagnosed individuals, many of whom never entered care following diagnosis or entered care but then dropped out. The presence of inmates throughout the HIV/AIDS continuum of care suggests that jails can play a strategic role in engaging persons living with HIV and AIDS in care. In order to be successful in structuring HIV/AIDS programs in jails, health care and correctional officials will be well-served to: (1) understand the HIV/AIDS continuum of care from the standpoint of engagement interventions that promote participation; (2) be aware of jail, community, and prison interventions that promote engagement in care; (3) anticipate and plan for the unique barriers jails provide in implementing engagement interventions; and, (4) be creative in designing engagement interventions suitable for both newly and previously diagnosed individuals.

  16. Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.

    Science.gov (United States)

    Santra, Sampa; Tomaras, Georgia D; Warrier, Ranjit; Nicely, Nathan I; Liao, Hua-Xin; Pollara, Justin; Liu, Pinghuang; Alam, S Munir; Zhang, Ruijun; Cocklin, Sarah L; Shen, Xiaoying; Duffy, Ryan; Xia, Shi-Mao; Schutte, Robert J; Pemble Iv, Charles W; Dennison, S Moses; Li, Hui; Chao, Andrew; Vidnovic, Kora; Evans, Abbey; Klein, Katja; Kumar, Amit; Robinson, James; Landucci, Gary; Forthal, Donald N; Montefiori, David C; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L; Michael, Nelson L; Kim, Jerome H; Soderberg, Kelly A; Giorgi, Elena E; Blair, Lily; Korber, Bette T; Moog, Christiane; Shattock, Robin J; Letvin, Norman L; Schmitz, Joern E; Moody, M A; Gao, Feng; Ferrari, Guido; Shaw, George M; Haynes, Barton F

    2015-08-01

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

  17. Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

    Directory of Open Access Journals (Sweden)

    Davide Corti

    2010-01-01

    Full Text Available The isolation of human monoclonal antibodies (mAbs that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine.We immortalized IgG(+ memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16 specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194 bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20 with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity.This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.

  18. Temporal variation in HIV-specific IgG subclass Abs during acute infection differentiates spontaneous controllers from chronic progressors.

    Science.gov (United States)

    Sadanand, Saheli; Das, Jishnu; Chung, Amy W; Schoen, Matthew K; Lane, Sophie; Suscovich, Todd J; Streeck, Hendrik; Smith, Davey; Little, Susan; Lauffenburger, Douglas A; Richman, Douglas; Alter, Galit

    2017-12-12

    Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between subjects who ultimately became controllers versus those who became progressors. IgG was purified from plasma from nine acutely infected subjects who subsequently controlled HIV spontaneously (controllers) and ten acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 post-infection. Levels of clade B gp120-, gp140-and gp41-specific IgG antibody subclasses were measured. Additionally, gp120-specific antibody-dependent cellular phagocytosis (ADCP), rapid fluorescent antibody-dependent cellular cytotoxicity (RFADCC), and antibody-dependent cellular viral inhibition (ADCVI) were all assessed. While no single Ab-related measurement was significantly associated with long-term HIV control, combinations of Ab-associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 Abs and losses in Env-specific IgG3 Abs. Moreover, progressors, but not controllers, lost ADCVI function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection. This study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir.

  19. Transgender women and HIV-related health disparities: falling off the HIV treatment cascade.

    Science.gov (United States)

    Kalichman, Seth C; Hernandez, Dominica; Finneran, Stephanie; Price, Devon; Driver, Redd

    2017-10-01

    Background Transgender women living with HIV infection experience poorer health outcomes across the HIV continuum of care. While disparities are well established, their underlying mechanisms are not well understood. This study examined the HIV continuum of care (also known as the HIV treatment cascade), including linkage and engagement in care and health status among transgender women and cisgender women and cisgender men living with HIV. Case-control matching was applied to a cohort of 1101 people living with HIV; 70 transgender women living with HIV were matched on years since testing HIV positive with cisgender women and cisgender men. Participants provided measures indicative of the HIV treatment cascade that included linkage and engagement in care, receiving and adhering to antiretroviral therapy (ART), and HIV viral suppression. Common correlates of HIV-related health status: depression symptoms, HIV-related stress, alcohol and drug use, healthcare conspiracy beliefs, medical mistrust, emotional social support and tangible social support, were also assessed. Transgender women were significantly less likely to receive ART, were less adherent to ART and had poorer HIV viral suppression than cisgender persons. Multivariable models demonstrated that health disparities were predicted by transgender women having poorer tangible social support over and above the other correlates of health outcomes. Tangible support is amenable by interventions such as building and strengthening supportive networks and paraprofessional services. Socially supportive interventions should be considered critical in efforts to decrease HIV health disparities among transgender women.

  20. HIV treatment beliefs and sexual transmission risk behaviors among HIV positive men and women.

    Science.gov (United States)

    Kalichman, Seth C; Eaton, Lisa; Cain, Demetria; Cherry, Charsey; Pope, Howard; Kalichman, Moira

    2006-10-01

    People are living longer and healthier with HIV infection because of successful combination antiretroviral therapies. HIV treatment beliefs are often associated with sexual practices among people living with HIV/AIDS but these associations may depend on the HIV status of sex partners. In a sample of 158 HIV positive men and women who were receiving HIV treatments, we examined the association between HIV treatment beliefs, HIV transmission risk perceptions, medication adherence, viral load and engaging in unprotected intercourse with any sex partners and specifically with sex partners who were not HIV positive (non-concordant). Results showed having missed medications in the past two days and treatment-related beliefs were significantly associated with engaging in unprotected intercourse with all sex partners as well as non-concordant partners. However, multivariate models showed that only treatment beliefs were significantly associated with engaging in unprotected intercourse with non-concordant partners. These results extend past research by demonstrating that the HIV status of sex partners sets the context for whether prevention-related treatment beliefs are associated with HIV transmission risk behaviors among people living with HIV/AIDS.

  1. Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies

    Directory of Open Access Journals (Sweden)

    Grupping Katrijn

    2009-12-01

    Full Text Available Abstract Background A minority of HIV-1 infected individuals develop broad cross-neutralizing (BCN plasma antibodies that are capable of neutralizing a spectrum of virus variants belonging to different HIV-1 clades. The aim of this study was to identify the targeted epitopes of an individual with BCN plasma antibodies, referred to as ITM4, using peptide phage display. This study also aimed to use the selected mimotopes as tools to unravel the evolution of the antibody landscape and the viral envelope escape which may provide us with new insights for vaccine design. Results This study led us to identify ITM4 plasma antibodies directed to the 4E10 epitope located in the gp41 membrane-proximal external region (MPER. Analysis of antibody specificities revealed unusual immunogenic properties of the ITM4 viral envelope, as not only the V3 loop and the gp41 MPER but also the C1 and lentivirus lytic peptide 2 (LLP2 region seem to be targets of the immune system. The 4E10-like antibodies are consistently elicited during the 6-year follow up period. HIV-1 ITM4 pseudoviruses showed an increasing resistance over time to MPER monoclonal antibodies 4E10 and 2F5, although no changes are found in the critical positions of the epitope. Neutralization of COT6.15 (subtype C; 4E10-sensitive pseudoviruses with alanine substitutions in the MPER region indicated an overlapping specificity of the 4E10 monoclonal antibody and the ITM4 follow up plasma. Moreover the 4E10-like antibodies of ITM4 contribute to the BCN capacity of the plasma. Conclusions Using ITM4 BCN plasma and peptide phage display technology, we have identified a patient with 4E10-like BCN antibodies. Our results indicate that the elicited 4E10-like antibodies play a role in virus neutralization. The viral RNA was isolated at different time points and the ITM4 envelope sequence analysis of both early (4E10-sensitive and late (4E10-resistant viruses suggest that other regions in the envelope, outside the

  2. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

    Directory of Open Access Journals (Sweden)

    Elise Landais

    2016-01-01

    Full Text Available Broadly neutralizing antibodies (bnAbs are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(- genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

  3. New crown motif of an HIV-1 V3 loop sequence from a Ugandan AIDS patient.

    Science.gov (United States)

    von Brunn, A; von Brunn, B; Eberle, J; Biryahwaho, B; Downing, R G; Gürtler, L

    1995-01-01

    HIV-1 V3 loop sequences from Ugandan patients include motifs from subtypes A, B, and D. To characterize further HIV isolates, V3 loop sequences were amplified from HIV-1 isolated in 1987 from peripheral blood mononuclear cells (PBL) of three patients with full-blown AIDS from Kampala, Uganda. The PBL were separated by Ficoll Paque gradients and cocultivated with noninfected donor lymphocytes for two weeks. The HIV was then transferred to HUT-78 cells. From extracted DNA of the permanently-infected HUT-78 cells, nested polymerase chain reaction (PCR) was conducted, with V3 loop sequencing performed directly upon PCR fragments derived from two independent DNA preparations and on cloned fragments. Isolates MVP-9801, -9802, and -9803 show 35.6%, 32.4%, and 29.7% nucleotide sequence divergence from the ELI subtype D sequence; 31.5%, 25.7%, and 18.9% divergence from the Z2Z6 subtype D sequence; and 21.9%, 12.2%, and 12.2% divergence from the subtype D consensus sequence. All three deduced amino acid sequences fit into the subtype D consensus sequence rather than into other V3 loop sequences described for Ugandan subtype A isolates. MVP-9802 and MVP-9803 contain the GSGQA pentapeptide motif at the tip of the V3 loop, while MVP-9801 contains GGRA. This may be explained by a deletion of proline codon between the codons for the two glycine residues. The authors believe that this deletion has not been previously reported. They also note that the deletion does not appear to be associated with a growth difference in vitro or with a difference in pathogenicity in vivo. The immunogenic implications of this altered V3 loop crest remain unclear. The Western blot profiles for the gp160, gp120, and gp41 proteins of the three Ugandan isolates manifest normal molecular weights.

  4. Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8.

    Directory of Open Access Journals (Sweden)

    Cinque Soto

    Full Text Available Antibody 10E8 targets the membrane-proximal external region (MPER of HIV-1 gp41, neutralizes >97% of HIV-1 isolates, and lacks the auto-reactivity often associated with MPER-directed antibodies. The developmental pathway of 10E8 might therefore serve as a promising template for vaccine design, but samples from time-of-infection-often used to infer the B cell record-are unavailable. In this study, we used crystallography, next-generation sequencing (NGS, and functional assessments to infer the 10E8 developmental pathway from a single time point. Mutational analysis indicated somatic hypermutation of the 2nd-heavy chain-complementarity determining region (CDR H2 to be critical for neutralization, and structures of 10E8 variants with V-gene regions reverted to genomic origin for heavy-and-light chains or heavy chain-only showed structural differences >2 Å relative to mature 10E8 in the CDR H2 and H3. To understand these developmental changes, we used bioinformatic sieving, maximum likelihood, and parsimony analyses of immunoglobulin transcripts to identify 10E8-lineage members, to infer the 10E8-unmutated common ancestor (UCA, and to calculate 10E8-developmental intermediates. We were assisted in this analysis by the preservation of a critical D-gene segment, which was unmutated in most 10E8-lineage sequences. UCA and early intermediates weakly bound a 26-residue-MPER peptide, whereas HIV-1 neutralization and epitope recognition in liposomes were only observed with late intermediates. Antibody 10E8 thus develops from a UCA with weak MPER affinity and substantial differences in CDR H2 and H3 from the mature 10E8; only after extensive somatic hypermutation do 10E8-lineage members gain recognition in the context of membrane and HIV-1 neutralization.

  5. Sensitive Next-Generation Sequencing Method Reveals Deep Genetic Diversity of HIV-1 in the Democratic Republic of the Congo.

    Science.gov (United States)

    Rodgers, Mary A; Wilkinson, Eduan; Vallari, Ana; McArthur, Carole; Sthreshley, Larry; Brennan, Catherine A; Cloherty, Gavin; de Oliveira, Tulio

    2017-03-15

    As the epidemiological epicenter of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43.02%), but 7 other subtypes (33.14%), 20 circulating recombinant forms (CRFs; 11.63%), and 20 unclassified (11.63%) sequences were also found. Of the rare and unclassified subtypes, 18 specimens were selected for next-generation sequencing (NGS) by a modified HIV-switching mechanism at the 5' end of the RNA template (SMART) method to obtain full-genome sequences. NGS produced 14 new complete genomes, which included pure subtype C (n = 2), D (n = 1), F1 (n = 1), H (n = 3), and J (n = 1) genomes. The two subtype C genomes and one of the subtype H genomes branched basal to their respective subtype branches but had no evidence of recombination. The remaining 6 genomes were complex recombinants of 2 or more subtypes, including subtypes A1, F, G, H, J, and K and unclassified fragments, including one subtype CRF25 isolate, which branched basal to all CRF25 references. Notably, all recombinant subtype H fragments branched basal to the H clade. Spatial-geographical analysis indicated that the diverse sequences identified here did not expand globally. The full-genome and subgenomic sequences identified in our study population significantly increase the documented diversity of the strains involved in the continually evolving HIV-1 pandemic.IMPORTANCE Very little is known about the ancestral HIV-1 strains that founded the global pandemic, and very few complete genome sequences are available from patients in the Congo Basin, where HIV-1 expanded early in the global pandemic. By

  6. HIV Clients as Agents for Prevention: A Social Network Solution

    Directory of Open Access Journals (Sweden)

    Sarah Ssali

    2012-01-01

    Full Text Available HIV prevention efforts to date have not explored the potential for persons living with HIV to act as change agents for prevention behaviour in their social networks. Using egocentric social network analysis, this study examined the prevalence and social network correlates of prevention advocacy behaviours (discussing HIV in general; encouraging abstinence or condom use, HIV testing, and seeking HIV care enacted by 39 HIV clients in Uganda. Participants engaged in each prevention advocacy behaviour with roughly 50–70% of the members in their network. The strongest determinant of engaging in prevention advocacy with more of one’s network members was having a greater proportion of network members who knew one’s HIV seropositive status, as this was associated with three of the four advocacy behaviours. These findings highlight the potential for PLHA to be key change agents for HIV prevention within their networks and the importance of HIV disclosure in facilitating prevention advocacy.

  7. HIV Prevention

    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 | ... Collapse All Is abstinence the only 100% effective HIV prevention option? Yes. Abstinence means not having oral, ...

  8. 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 ...

  9. Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity.

    Directory of Open Access Journals (Sweden)

    Leen Mathys

    Full Text Available N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. We show here that gp160 containing the N260Q mutation reaches the Golgi apparatus during biosynthesis. Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N that could partially restore the infectivity of mutant N260Q gp120 virus. However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. Moreover, at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation reached a conformation that enabled CD4 binding.

  10. Functional stability of unliganded envelope glycoprotein spikes among isolates of human immunodeficiency virus type 1 (HIV-1.

    Directory of Open Access Journals (Sweden)

    Nitish Agrawal

    Full Text Available The HIV-1 envelope glycoprotein (Env spike is challenging to study at the molecular level, due in part to its genetic variability, structural heterogeneity and lability. However, the extent of lability in Env function, particularly for primary isolates across clades, has not been explored. Here, we probe stability of function for variant Envs of a range of isolates from chronic and acute infection, and from clades A, B and C, all on a constant virus backbone. Stability is elucidated in terms of the sensitivity of isolate infectivity to destabilizing conditions. A heat-gradient assay was used to determine T(90 values, the temperature at which HIV-1 infectivity is decreased by 90% in 1 h, which ranged between ∼40 to 49°C (n = 34. For select Envs (n = 10, the half-lives of infectivity decay at 37°C were also determined and these correlated significantly with the T(90 (p = 0.029, though two 'outliers' were identified. Specificity in functional Env stability was also evident. For example, Env variant HIV-1(ADA was found to be labile to heat, 37°C decay, and guanidinium hydrochloride but not to urea or extremes of pH, when compared to its thermostable counterpart, HIV-1(JR-CSF. Blue native PAGE analyses revealed that Env-dependent viral inactivation preceded complete dissociation of Env trimers. The viral membrane and membrane-proximal external region (MPER of gp41 were also shown to be important for maintaining trimer stability at physiological temperature. Overall, our results indicate that primary HIV-1 Envs can have diverse sensitivities to functional inactivation in vitro, including at physiological temperature, and suggest that parameters of functional Env stability may be helpful in the study and optimization of native Env mimetics and vaccines.

  11. Stigma, Activism, and Well-Being among People Living with HIV

    OpenAIRE

    Earnshaw, Valerie A.; Rosenthal, Lisa; Lang, Shawn M.

    2016-01-01

    Evidence demonstrates that HIV stigma undermines the psychological and physical health of people living with HIV (PLWH). Yet, PLWH describe engaging in HIV activism to challenge stigma, and research suggests that individuals may benefit from activism. We examine associations between experiences of HIV stigma and HIV activism, and test whether HIV activists benefit from greater well-being than non-activists. Participants include 93 PLWH recruited from drop-in centers, housing programs, and oth...

  12. High Levels of Inflammatory Cytokines in the Reproductive Tract of Women with BV and Engaging in Intravaginal Douching: A Cross-Sectional Study of Participants in the Women Interagency HIV Study.

    Science.gov (United States)

    Alcaide, Maria L; Rodriguez, Violeta J; Brown, Megan R; Pallikkuth, Suresh; Arheart, Kristopher; Martinez, Octavio; Roach, Margaret; Fichorova, Raina N; Jones, Deborah L; Pahwa, Savita; Fischl, Margaret A

    2017-04-01

    High levels of inflammatory cytokines in the genital tract suggest mucosal vulnerability and increased risk of HIV and sexually transmitted infection (STI) acquisition. Intravaginal douching is associated with bacterial vaginosis (BV) in women in the United States, and both douching and BV are linked to HIV and STI acquisition. This study evaluates inflammatory cytokines in the genital tract to increase understanding of the effects of both BV and intravaginal douching to the vaginal mucosa. A cross-sectional study of participants in the Miami WIHS investigated 72 reproductive age women (45 HIV + and 27 high-risk HIV - ) who completed intravaginal douching questionnaires and underwent collection of vaginal swabs and cervicovaginal lavages (CVLs). BV was assessed using the Nugent score. Inflammatory cytokines in the CVLs (interleukin [IL]-6, IL-8, IL-1α, IL-1β, soluble intracellular adhesion molecule-1 [sICAM-1], interferon [IFN]α2, chemokine C ligand 5 (CCL5), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP1), tumor necrosis factor alpha (TNFα), and secretory leukocyte protease inhibitor [SLPI]) were measured. Fourteen (19%) women reported intravaginal douching; 24 (33%) had BV. BV, intravaginal douching, and HIV were associated with higher levels of inflammatory cytokines. After controlling for demographic and risk factors and HIV status, women who had BV and douched had higher levels of inflammatory cytokines than those without BV and who did not douche, or who only had BV or only douched. These findings suggest that BV and douching are associated with greater mucosal inflammation and may facilitate HIV acquisition and transmission. Although longitudinal studies are needed to determine temporal associations and causality, interventions to decrease rates of intravaginal douching and BV could significantly decrease women's risks of acquiring STIs and HIV and limit the spread of HIV.

  13. HIV/AIDS Adherence: Teaching about Treatment and Stigma

    Science.gov (United States)

    Curtis, Jena Nicols

    2008-01-01

    Advances in HIV/AIDS treatment have dramatically changed the nature of HIV/AIDS education and prevention, creating new opportunities and challenges. This activity is designed to help participants reflect on the impact that HIV treatment can have on a person's life. It also enables trainers to engage participants in a dialogue about the impact of…

  14. Reticence in disclosure of HIV infection and reasons for bereavement

    African Journals Online (AJOL)

    Reticence in disclosure of HIV infection and reasons for bereavement: impact on perinatally infected adolescents' mental health and understanding of HIV treatment ... engagement in the process of disclosure of HIV status is necessary to reduce stigma and complicated grieving, and improve mental health in this population.

  15. The gp41659 - 671 HIV-1 antibody epitope: a structurally challenging small peptide

    Science.gov (United States)

    Zhang, Yuan; Sagui, Celeste

    2014-03-01

    We present the results of extensive Molecular Dynamics (MD) simulations of the tridecapeptide corresponding to residues 659-671 of the envelope glycoprotein gp41 of HIV-1, which spans the 2F5 monoclonal antibody epitope ELDKWA. The most recent AMBER force fields ff99SB and ff12SB in both implicit and explicit solvents have been used for a cumulative time longer than 7.2 μs . We have analyzed the conformational ensembles of the peptide both with and without applied tensile restraints, and found that: (1) The amount of helical populations is important in aqueous solution, but this structure forms part of a flexible conformational ensemble with a rugged free energy landscape with shallow minima, which agrees well with the bulk of the experimental observations; (2) our results are more consistent with the experimental results than those from previous simulations; (3) under uniaxial tension, the disordered peptide first becomes fully helical before melting into turns, loops and 310-helices.

  16. Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

    Directory of Open Access Journals (Sweden)

    Alba Torrents de la Peña

    2017-08-01

    Full Text Available The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs.

  17. Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies.

    Directory of Open Access Journals (Sweden)

    Laura E McCoy

    2015-08-01

    Full Text Available The broadly neutralizing HIV monoclonal antibodies (bnMAbs PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4 assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high-mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design.

  18. Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

    Directory of Open Access Journals (Sweden)

    Damien C Tully

    2016-05-01

    Full Text Available Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU, we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

  19. Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

    Science.gov (United States)

    Tully, Damien C; Ogilvie, Colin B; Batorsky, Rebecca E; Bean, David J; Power, Karen A; Ghebremichael, Musie; Bedard, Hunter E; Gladden, Adrianne D; Seese, Aaron M; Amero, Molly A; Lane, Kimberly; McGrath, Graham; Bazner, Suzane B; Tinsley, Jake; Lennon, Niall J; Henn, Matthew R; Brumme, Zabrina L; Norris, Philip J; Rosenberg, Eric S; Mayer, Kenneth H; Jessen, Heiko; Kosakovsky Pond, Sergei L; Walker, Bruce D; Altfeld, Marcus; Carlson, Jonathan M; Allen, Todd M

    2016-05-01

    Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

  20. Synthetic peptides derived from an N-terminal domain of the E2 protein of GB virus C in the study of GBV-C/HIV-1 co-infection.

    Science.gov (United States)

    Fernández, Leticia; Chan, Weng C; Egido, Meritxell; Gómara, María J; Haro, Isabel

    2012-05-01

    Synthetic peptides derived from GB virus C (GBV-C) have previously been studied in our group for the development of new systems capable of diagnosing diseases caused by this humanotropic virus. We also recently described specific peptide domains of the E2 envelop protein of GBV-C that have the capacity to interfere with the HIV-1 fusion peptide, produce a notable decrease in cellular membrane fusion, and perturb HIV-1 infectivity in a dose-dependent manner. The present work discloses the design and synthesis of both linear and cyclic branched peptides based on a previously reported N-terminal sequence of the GBV-C E2 protein. Immunoassays and cell-cell fusion assays were performed to evaluate their diagnostic value to detect anti-GBV-C antibodies in HIV-1 patients, as well as their putative anti-HIV-1 activity as entry inhibitors. Our results showed that chemical modifications of the selected E2(7-26) linear peptide to afford cyclic architecture do not result in an enhanced inhibition of gp41 HIV-1-mediated cell-cell fusion nor improved sensitivity in the detection of GBV-C antibodies in HIV-1 co-infected patients. Thus, the ELISA data reinforce the potential utility of linear versions of the E2(7-26) region for the development of new peptide-based immunosensor devices for the detection of anti-GBV-C antibodies in HIV-1 co-infected patients. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  1. Socially responsible investment engagement

    NARCIS (Netherlands)

    Goessling, T.; Buijter, Bas; Freeman, R.E.; Kujala, J.; Sachs, S.

    2017-01-01

    This study explores engagement in socially responsible investment (SRI) processes. More specifically, it researches the impact of shareholder salience on the success of engagement activities. The research question asks: What is the relationship between shareholder salience and engagement effort

  2. A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.

    Science.gov (United States)

    Meador, Lydia R; Kessans, Sarah A; Kilbourne, Jacquelyn; Kibler, Karen V; Pantaleo, Giuseppe; Roderiguez, Mariano Esteban; Blattman, Joseph N; Jacobs, Bertram L; Mor, Tsafrir S

    2017-07-01

    Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Design and In Vivo Characterization of Immunoconjugates Targeting HIV gp160

    Science.gov (United States)

    Song, Kejing; Maresh, Grace A.; Frank, Anderson; Worthylake, David; Chung, Hye-Kyung; Polacino, Patricia; Hamer, Dean H.; Coyne, Cody P.; Rosenblum, Michael G.; Marks, John W.; Chen, Gang; Weiss, Deborah; Ghetie, Victor; Vitetta, Ellen S.; Robinson, James E.; Hu, Shiu-Lok

    2016-01-01

    ABSTRACT The envelope (Env) glycoprotein of HIV is expressed on the surface of productively infected cells and can be used as a target for cytotoxic immunoconjugates (ICs), in which cell-killing moieties, including toxins, drugs, or radionuclides, are chemically or genetically linked to monoclonal antibodies (MAbs) or other targeting ligands. Such ICs could be used to eliminate persistent reservoirs of HIV infection. We have found that MAbs which bind to the external loop of gp41, e.g., MAb 7B2, make highly effective ICs, particularly when used in combination with soluble CD4. We evaluated the toxicity, immunogenicity, and efficacy of the ICs targeted with 7B2 in mice and in simian-human immunodeficiency virus-infected macaques. In the macaques, we tested immunotoxins (ITs), consisting of protein toxins bound to the targeting agent. ITs were well tolerated and initially efficacious but were ultimately limited by their immunogenicity. In an effort to decrease immunogenicity, we tested different toxic moieties, including recombinant toxins, cytotoxic drugs, and tubulin inhibitors. ICs containing deglycosylated ricin A chain prepared from ricin toxin extracted from castor beans were the most effective in killing HIV-infected cells. Having identified immunogenicity as a major concern, we show that conjugation of IT to polyethylene glycol limits immunogenicity. These studies demonstrate that cytotoxic ICs can target virus-infected cells in vivo but also highlight potential problems to be addressed. IMPORTANCE It is not yet possible to cure HIV infection. Even after years of fully effective antiviral therapy, a persistent reservoir of virus-infected cells remains. Here we propose that a targeted conjugate consisting of an anti-HIV antibody bound to a toxic moiety could function to kill the HIV-infected cells that constitute this reservoir. We tested this approach in HIV-infected cells grown in the lab and in animal infections. Our studies demonstrated that these

  4. HIV Life Cycle

    Science.gov (United States)

    ... healthier lives. ART also reduces the risk of HIV transmission (the spread of HIV to others). HIV attacks and destroys ... lives. HIV medicines also reduce the risk of HIV transmission (the spread of HIV to others). What are the seven ...

  5. 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 ...

  6. Treatment for HIV

    Science.gov (United States)

    ... and Public Home » Treatment » Treatment Decisions and HIV HIV/AIDS Menu Menu HIV/AIDS HIV/AIDS Home ... here Enter ZIP code here Treatment Decisions and HIV for Veterans and the Public Treatment for HIV: ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... she went to a party and under the influence of drugs and alcohol engaged in risky sexual ... learn-link-drugs-hiv . 120x90 460x80 486x60 Social Media Send the message to young people and to ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with drug abuse are among the main factors in the ... who engage in drug use or high-risk behaviors associated with drug use also put themselves at risk for contracting ...

  9. Maturation of HIV envelope glycoprotein precursors by cellular endoproteases.

    Science.gov (United States)

    Moulard, M; Decroly, E

    2000-11-10

    . Furthermore, relationships between differential pathogenicity of influenza strains and their susceptibility to cleavage are molecularly funded. Here we review the most recent data and recent insights demonstrating the crucial role played by this activation step in virus infectivity. We discuss the cellular endoproteases that are implicated in HIV gp160 endoproteolytical maturation into gp120 and gp41.

  10. Sexual HIV risk behaviors in a treatment-refractory opioid-dependent sample.

    Science.gov (United States)

    McHugh, R Kathryn; Weitzman, Meara; Safren, Steven A; Murray, Heather W; Pollack, Mark H; Otto, Michael W

    2012-01-01

    The propensity to engage in risk behaviors confers an elevated risk of HIV and other infectious disease transmission in opioid-dependent populations. Although drug abuse treatment may decrease drug-related risk behaviors such as needle-sharing, additional intervention may be needed to reduce HIV risk behavior. In this investigation, we assessed sexual HIV risk behaviors in opioid-dependent patients who were engaging in regular drug use despite ongoing counseling and methadone maintenance therapy. Potential risk and protective factors for engaging in sexual HIV risk behavior were examined. Taking into account demographic, psychiatric, substance use, and psychological variables, the only significant predictor of risk behavior was age. Specifically, younger patients were more likely to engage in sexual HIV risk behavior. The implications of these results for reducing sexual HIV risk behavior and for HIV prevention in methadone-maintained, treatment-refractory opioid-dependent patients are discussed.

  11. Substance use and HIV infection awareness among HIV-infected female sex workers in Lilongwe, Malawi.

    Science.gov (United States)

    Lancaster, Kathryn E; Go, Vivian F; Lungu, Thandie; Mmodzi, Pearson; Hosseinipour, Mina C; Chadwick, Katy; Powers, Kimberly A; Pence, Brian W; Hoffman, Irving F; Miller, William C

    2016-04-01

    HIV diagnosis, the first step in HIV care and treatment engagement, may be inhibited by substance use among female sex workers (FSW). We assessed the relationship between alcohol and cannabis use and lack of HIV infection awareness among HIV-infected FSW in Lilongwe, Malawi. From July to September, 2014, 200 FSW aged ≥18 years were enrolled using venue-based sampling to examine substance use, HIV testing history, and serostatus ascertained by HIV rapid test. We used Poisson regression with robust variance estimates to estimate the associations of alcohol and cannabis use and lack of HIV infection awareness. Of the 138 HIV-infected FSW, 20% were unaware of their HIV infection, with 70% not testing within 6 months prior. According to the Alcohol Use Disorder Identification Tests (AUDIT), 55% of FSW unaware of their HIV infection reported hazardous, harmful, or dependent alcohol consumption. We observed a dose-response relationship between alcohol use and lack of HIV infection awareness, with alcohol dependency significantly associated with lack of HIV infection awareness (adjusted prevalence ratio: 3.0, 95% CI: 1.3, 6.8). Current cannabis use was uncommon (26%) among unaware HIV-infected FSW and weakly associated with lack of HIV infection awareness adjusted prevalence ratio: 1.1, 95% CI: 0.5, 2.5). Increased levels of alcohol use is associated with lack of HIV infection awareness among HIV-infected FSW in Malawi. Frequent, consistent HIV testing integrated with alcohol reduction strategies could improve the health and infection awareness of substance-using FSW. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry.

    Directory of Open Access Journals (Sweden)

    Rachid Sougrat

    2007-05-01

    Full Text Available The envelope glycoproteins of primate lentiviruses, including human and simian immunodeficiency viruses (HIV and SIV, are heterodimers of a transmembrane glycoprotein (usually gp41, and a surface glycoprotein (gp120, which binds CD4 on target cells to initiate viral entry. We have used electron tomography to determine the three-dimensional architectures of purified SIV virions in isolation and in contact with CD4+ target cells. The trimeric viral envelope glycoprotein surface spikes are heterogeneous in appearance and typically approximately 120 A long and approximately 120 A wide at the distal end. Docking of SIV or HIV-1 on the T cell surface occurs via a neck-shaped contact region that is approximately 400 A wide and consistently consists of a closely spaced cluster of five to seven rod-shaped features, each approximately 100 A long and approximately 100 A wide. This distinctive structure is not observed when viruses are incubated with T lymphocytes in the presence of anti-CD4 antibodies, the CCR5 antagonist TAK779, or the peptide entry inhibitor SIVmac251 C34. For virions bound to cells, few trimers were observed away from this cluster at the virion-cell interface, even in cases where virus preparations showing as many as 70 envelope glycoprotein trimers per virus particle were used. This contact zone, which we term the "entry claw", provides a spatial context to understand the molecular mechanisms of viral entry. Determination of the molecular composition and structure of the entry claw may facilitate the identification of improved drugs for the inhibition of HIV-1 entry.

  13. Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach.

    Science.gov (United States)

    Franquelim, Henri G; Gaspar, Diana; Veiga, A Salomé; Santos, Nuno C; Castanho, Miguel A R B

    2013-08-01

    Enfuvirtide and T-1249 are two potent HIV-1 fusion inhibitor peptides. Recent studies indicate that lipids play an important role in the mode of action of those bioactive molecules. Using a combined tandem atomic force microscopy (AFM)-epifluorescence microscopy approach, we studied the interaction of both enfuvirtide and T-1249 with supported lipid bilayers. Fluid (ld)-gel (so) and ld-liquid ordered (lo) phase-separated membrane systems were tested. Results, especially for T-1249, show significant lipid membrane activity at a 15μM peptide concentration. T-1249, in opposition to enfuvirtide, induces an increase in membrane surface roughness, decrease in membrane fluidity, bilayer thinning at ld domains and disruption of the so domain borders. In terms of structural properties, both enfuvirtide and T-1249 possess distinct functional hydrophobic and amphipathic domains of HIV gp41. While enfuvirtide only yields the tryptophan-rich domain (TRD), T-1249 possesses both TRD and pocket-binding domain (PBD). TRD increases the hydrophobicity of the peptide while PBD enhances the amphipathic characteristics. As such, the enhanced membrane activity of T-1249 may be explained by a synergism between its amphipathic N-terminal segment and its hydrophophic C-terminal. Our findings provide valuable insights on the molecular-level mode of action of HIV-1 fusion inhibitors, unraveling the correlation between their structural properties and membrane interactions as a factor influencing their antiviral activity. Ultimately, this work validates the applicability of a combined AFM and fluorescence approach to evaluate the mechanic and structural properties of supported lipid bilayers upon interaction with membrane-active peptides. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Neutralizing antibody escape during HIV-1 mother-to-child transmission involves conformational masking of distal epitopes in envelope.

    Science.gov (United States)

    Goo, Leslie; Milligan, Caitlin; Simonich, Cassandra A; Nduati, Ruth; Overbaugh, Julie

    2012-09-01

    HIV-1 variants transmitted to infants are often resistant to maternal neutralizing antibodies (NAbs), suggesting that they have escaped maternal NAb pressure. To define the molecular basis of NAb escape that contributes to selection of transmitted variants, we analyzed 5 viruses from 2 mother-to-child transmission pairs, in which the infant virus, but not the maternal virus, was resistant to neutralization by maternal plasma near transmission. We generated chimeric viruses between maternal and infant envelope clones obtained near transmission and examined neutralization by maternal plasma. The molecular determinants of NAb escape were distinct, even when comparing two maternal variants to the transmitted infant virus within one pair, in which insertions in V4 of gp120 and substitutions in HR2 of gp41 conferred neutralization resistance. In another pair, deletions and substitutions in V1 to V3 conferred resistance, but neither V1/V2 nor V3 alone was sufficient. Although the sequence determinants of escape were distinct, all of them involved modifications of potential N-linked glycosylation sites. None of the regions that mediated escape were major linear targets of maternal NAbs because corresponding peptides failed to compete for neutralization. Instead, these regions disrupted multiple distal epitopes targeted by HIV-1-specific monoclonal antibodies, suggesting that escape from maternal NAbs occurred through conformational masking of distal epitopes. This strategy likely allows HIV-1 to utilize relatively limited changes in the envelope to preserve the ability to infect a new host while simultaneously evading multiple NAb specificities present in maternal plasma.

  15. Neutralization of X4- and R5-tropic HIV-1 NL4-3 variants by HOCl-modified serum albumins

    Directory of Open Access Journals (Sweden)

    Schwalbe Birco

    2010-06-01

    Full Text Available Abstract Background Myeloperoxidase (MPO, an important element of the microbicidal activity of neutrophils, generates hypochlorous acid (HOCl from H2O2 and chloride, which is released into body fluids. Besides its direct microbicidal activity, HOCl can react with amino acid residues and HOCl-modified proteins can be detected in vivo. Findings This report is based on binding studies of HOCl-modified serum albumins to HIV-1 gp120 and three different neutralization assays using infectious virus. The binding studies were carried out by surface plasmon resonance spectroscopy and by standard ELISA techniques. Virus neutralization assays were carried out using HIV-1 NL4-3 virus and recombinant strains with CXCR4 and CCR5 coreceptor usage. Viral infection was monitored by a standard p24 or X-gal staining assay. Our data demonstrate that HOCl-modified mouse-, bovine- and human serum albumins all bind to the HIV-1 NL4-3 gp120 (LAV glycoprotein in contrast to non-modified albumin. Binding of HOCl-modified albumin to gp120 correlated to the blockade of CD4 as well as that of V3 loop specific monoclonal antibody binding. In neutralization experiments, HOCl-modified serum albumins inhibited replication and syncytium formation of the X4- and R5-tropic NL4-3 isolates in a dose dependent manner. Conclusions Our data indicate that HOCl-modified serum albumin veils the binding site for CD4 and the V3 loop on gp120. Such masking of the viral gp120/gp41 envelope complex might be a simple but promising strategy to inactivate HIV-1 and therefore prevent infection when HOCl-modified serum albumin is applied, for example, as a topical microbicide.

  16. Immunogenic Display of Purified Chemically Cross-Linked HIV-1 Spikes

    Science.gov (United States)

    Leaman, Daniel P.; Lee, Jeong Hyun; Ward, Andrew B.

    2015-01-01

    ABSTRACT HIV-1 envelope glycoprotein (Env) spikes are prime vaccine candidates, at least in principle, but suffer from instability, molecular heterogeneity and a low copy number on virions. We anticipated that chemical cross-linking of HIV-1 would allow purification and molecular characterization of trimeric Env spikes, as well as high copy number immunization. Broadly neutralizing antibodies bound tightly to all major quaternary epitopes on cross-linked spikes. Covalent cross-linking of the trimer also stabilized broadly neutralizing epitopes, although surprisingly some individual epitopes were still somewhat sensitive to heat or reducing agent. Immunodepletion using non-neutralizing antibodies to gp120 and gp41 was an effective method for removing non-native-like Env. Cross-linked spikes, purified via an engineered C-terminal tag, were shown by negative stain EM to have well-ordered, trilobed structure. An immunization was performed comparing a boost with Env spikes on virions to spikes cross-linked and captured onto nanoparticles, each following a gp160 DNA prime. Although differences in neutralization did not reach statistical significance, cross-linked Env spikes elicited a more diverse and sporadically neutralizing antibody response against Tier 1b and 2 isolates when displayed on nanoparticles, despite attenuated binding titers to gp120 and V3 crown peptides. Our study demonstrates display of cross-linked trimeric Env spikes on nanoparticles, while showing a level of control over antigenicity, purity and density of virion-associated Env, which may have relevance for Env based vaccine strategies for HIV-1. IMPORTANCE The envelope spike (Env) is the target of HIV-1 neutralizing antibodies, which a successful vaccine will need to elicit. However, native Env on virions is innately labile, as well as heterogeneously and sparsely displayed. We therefore stabilized Env spikes using a chemical cross-linker and removed non-native Env by immunodepletion with non

  17. "Learning the Basics": Young People's Engagement with Sexuality Education at Secondary Schools

    Science.gov (United States)

    Adams Tucker, Leigh; George, Gavin; Reardon, Candice; Panday, Saadhna

    2016-01-01

    School-based sexuality education remains a key response to the HIV epidemic. Drawing on findings from an ethnographic study, this study explores how young people engage with sexuality and HIV- and AIDS-related education as it is delivered through the Life Orientation (LO) learning area in South Africa, in order to understand the dynamics that…

  18. Mathematical Engagement Skills

    Science.gov (United States)

    Ingram, Naomi

    2013-01-01

    In this paper, the mathematical engagement of Colin and Robyn is compared. Through this comparison, and informed by longitudinal research into the mathematical journeys of a group of students in New Zealand, a set of engagement skills emerged. Both students had high levels of engagement in mathematics. However, Colin was a thriving mathematics…

  19. Engaging With Reality

    DEFF Research Database (Denmark)

    Bondebjerg, Ib

    to engage us with reality. Engaging with Reality investigates some of the major global themes as they are reflected in documentaries from the USA, UK and Denmark. Engaging with Reality is a contribution to comparative, transnational studies of documentary in contemporary media culture. By comparing...

  20. Engagement and Institutional Advancement

    Science.gov (United States)

    Weerts, David; Hudson, Elizabeth

    2009-01-01

    Research suggests that institutional commitment to community engagement can be understood by examining levels of student, faculty, and community involvement in engagement; organizational structure, rewards, and campus publications supporting engagement; and compatibility of an institution's mission with this work (Holland, 1997). Underlying all of…

  1. ?No More Buzz?: A Qualitative Study of the Current Response to HIV in the Anglican Church in the Western Cape, South Africa

    OpenAIRE

    Hallonsten, Simon

    2017-01-01

    Using a triangulation design combining participant observation, survey results, and interviews, this paper studies the current form of the response to HIV in the local Anglican Church in the Western Cape, South Africa. The results show that people are generally aware of HIV. The ?buzz? around HIV has, however, subsided. The local church does not directly engage HIV anymore, and HIV is more mentioned than talked about. HIV stigma continues to pose a challenge. To work towards the prevention of...

  2. The Experience of Sexual Risk Communication in African American Families Living with HIV

    Science.gov (United States)

    Cederbaum, Julie A.

    2012-01-01

    Mother-daughter communication plays an influential role in adolescent development. The impact of maternal HIV infection on family communication is not clear. This study explores how living with HIV impacts sexual risk communication between mothers and daughters and whether maternal HIV status influences adolescent choices about engagement in HIV…

  3. The Influence of Knowing Someone with AIDS on Youth HIV Sexual Risk Behaviors

    Science.gov (United States)

    Cederbaum, Julie A.; Marcus, Steven C.; Hutchinson, M. Katherine

    2007-01-01

    Research indicates that knowing someone with HIV/AIDS is associated with greater perceived risk of contracting HIV and changes in sexual risk behaviors. The current study with a sample of 1,172 examined whether knowing someone with HIV/AIDS influenced sexual risk communication and youth engagement in sexual intercourse using the Philadelphia…

  4. Designing for user engagement

    CERN Document Server

    Geisler, Cheryl

    2013-01-01

    Designing for User Engagement on the Web: 10 Basic Principles is concerned with making user experience engaging. The cascade of social web applications we are now familiar with - blogs, consumer reviews, wikis, and social networking - are all engaging experiences. But engagement is an increasingly common goal in business and productivity environments as well. This book provides a foundation for all those seeking to design engaging user experiences rich in communication and interaction. Combining a handbook on basic principles with case studies, it provides readers with a ric

  5. HIV sexual transmission risks in the context of clinical care: a prospective study of behavioural correlates of HIV suppression in a community sample, Atlanta, GA, USA

    Directory of Open Access Journals (Sweden)

    Seth C Kalichman

    2015-08-01

    Full Text Available Introduction: Antiretroviral therapy (ART improves the health of people living with HIV and has the potential to reduce HIV infectiousness, thereby preventing HIV transmission. However, the success of ART for HIV prevention hinges on sustained ART adherence and avoiding sexually transmitted infections (STI. Objectives: To determine the sexual behaviours and HIV transmission risks of individuals with suppressed and unsuppressed HIV replication (i.e., viral load. Methods: Assessed HIV sexual transmission risks among individuals with clinically determined suppressed and unsuppressed HIV. Participants were 760 men and 280 women living with HIV in Atlanta, GA, USA, who completed behavioural assessments, 28-daily prospective sexual behaviour diaries, one-month prospective unannounced pill counts for ART adherence, urine screening for illicit drug use and medical record chart abstraction for HIV viral load. Results: Individuals with unsuppressed HIV demonstrated a constellation of behavioural risks for transmitting HIV to uninfected sex partners that included symptoms of STI and substance use. In addition, 15% of participants with suppressed HIV had recent STI symptoms/diagnoses, indicating significant risks for sexual infectiousness despite their HIV suppression in blood plasma. Overall, 38% of participants were at risk for elevated sexual infectiousness and just as many engaged in unprotected sexual intercourse with non-HIV-infected partners. Conclusions: Implementation strategies for using HIV treatments as HIV prevention requires enhanced behavioural interventions that extend beyond ART to address substance use and sexual health that will otherwise undermine the potential preventive impact of early ART.

  6. 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

  7. Changes in gay men's participation in gay community life: implications for HIV surveillance and research.

    Science.gov (United States)

    Zablotska, Iryna B; Holt, Martin; Prestage, Garrett

    2012-04-01

    Successful antiretroviral treatments, achievements in gay acceptance and human rights, and internet use have prompted changes in gay socialising which create potential challenges for engaging with gay men for HIV surveillance and research. We used data from the Australian behavioural surveillance and explored (i) the relationship between community engagement and HIV related practices, and (ii) time trends in gay men's engagement with the gay community. Analyses were conducted using log-binomial regression and chi-square test for trend. The proportion of men who socialized mainly with gay men declined and the Internet use to connect with sex partners increased over time. Gay social engagement was associated with HIV positive serostatus, unprotected anal intercourse with regular partners and a high frequency of HIV/STI testing. Our findings indicate a shift in how gay men socialise and find partners. We discuss the challenges for ongoing engagement with gay men for behavioural surveillance and HIV research.

  8. 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.

  9. Implementation of a School-Based HIV Prevention Curriculum ...

    African Journals Online (AJOL)

    Boys who reported higher self-efficacy and learning about abstinence strategies engaged in lower risk behaviour , while exposure to HIV education in assemblies and communication with relatives about HIV was associated with higher risk. Conclusion: Previous studies documented benefits of PSABH. However, it is unclear ...

  10. Representations of HIV/AIDS management in South African ...

    African Journals Online (AJOL)

    Through an analysis of newspaper articles, we explore the dominant representations of HIV/AIDS management circulating in the South African public sphere and examine how community engagement is depicted. We highlight the way media representations reflect narrow understandings of HIV and AIDS as a predominantly ...

  11. Extramarital sexual practices and perceived association with HIV ...

    African Journals Online (AJOL)

    Despite evident association between such practice and spread in HIV infection, to date multiple sexual partnerships is a common practice. Among the Borana pastoral community, where awareness about HIV and AIDS is documented to be limited, engagement in extramarital sexual practice is believed to be the norm rather ...

  12. Prevalence and Public Health Implications of State Laws that Criminalize Potential HIV Exposure in the United States

    OpenAIRE

    Lehman, J. Stan; Carr, Meredith H.; Nichol, Allison J.; Ruisanchez, Alberto; Knight, David W; Langford, Anne E.; Gray, Simone C.; Mermin, Jonathan H.

    2014-01-01

    For the past three decades, legislative approaches to prevent HIV transmission have been used at the national, state, and local levels. One punitive legislative approach has been enactment of laws that criminalize behaviors associated with HIV exposure (HIV-specific criminal laws). In the USA, HIV-specific criminal laws have largely been shaped by state laws. These laws impose criminal penalties on persons who know they have HIV and subsequently engage in certain behaviors, most commonly sexu...

  13. Cross-border sexual transmission of the newly emerging HIV-1 clade CRF51_01B.

    Directory of Open Access Journals (Sweden)

    Hui Ting Cheong

    Full Text Available A novel HIV-1 recombinant clade (CRF51_01B was recently identified among men who have sex with men (MSM in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding

  14. Gestantes/puérperas com hiv/aids: conhecendo os déficits e os fatores que contribuem no engajamento para o autocuidado Gestantes/puérperas con el vih/sida: conociendo los déficits y los factores que contribuyen para el compromiso con el autocuidado Pregnant women/mothers with newborns with hiv/aids: understanding the deficits and factors that contribute to engaging in self-care

    Directory of Open Access Journals (Sweden)

    Lígia Maria Scherer

    2009-06-01

    ón social. Las gestantes/puérperas conviven con factores que contribuyen para el compromiso con el autocuidado, así como con factores que lo dificultan. Pero a pesar de las dificultades, ellas han conseguido sobrevivir al aislamiento y al prejuicio gracias al apoyo familiar y a la ayuda del equipo de salud, especialmente de las enfermeras.The objective of this qualitative, descriptive, exploratory study is to better understand the deficits of self-care among pregnant women/ mothers with newborns with HIV/AIDS and the factors that influence engagement with self-care. The study was carried out with ten pregnant women/mothers of newborns with HIV who use the Specialized Service for STD/Aids in Rio Grande do Sul, Brazil. The data was collected through a focus group and individual interviews, using a semi-structured script. After analyzing the data through content analysis, the following results were reached: the pregnant women/ mothers of newborns with HIV present deficits to self-care related to nutrition and feeding, water ingestion, sleep and rest, sexual life, leisure and recreation, and social interaction. They live so continuously with factors that contribute to engaging in self-care as factors that make this process difficult. Even with these difficulties, the pregnant women/ mothers of newborns have been able to survive into the isolation, the prejudice, receiving a support from their families and from the health care team, especially from nurses.

  15. The role of social relationship in HIV healing and its implications in HIV cure in China.

    Science.gov (United States)

    Qiao, Shan; Nie, Jing-Bao; Tucker, Joseph; Rennie, Stuart; Li, Xiao-Ming

    HIV is both a biomedical disease and a social phenomenon that is constructed in particular cultural contexts. A successful and humane HIV cure requires not only the science of eradicating pathogens, but also the art of healing to restore harmony between mind and body. Healing in the context of HIV cure will be both personal and interpersonal, biological and social, and will involve rebuilding connections between HIV patients and their social environment. Social conceptions of healing have been highlighted in many regions with rich non-biomedical healing traditions, including China. Based on an adapted theoretical model on social relationships and health, we address the essential role of social relations for HIV healing in Chinese cultural context, and propose several recommendations for reforming practices and policies regarding HIV healing. In general, family is still a core social unit in HIV patients' medical journey from diagnosis to treatment. A positive patient-physician relationship based on mutual respect and trust also has critical impact on patients' physical and mental health. Physicians may become a key or the main source of social support in circumstances when families are not actively engaged in healing. Reconnecting HIV patients with their communities should be a necessary component of HIV cure, as this will help patients engage more fully in the HIV healing process. We call for a family-centered approach in HIV healing intervention to strengthen patient-family ties; a series of policies to build up and sustain positive patient-physician ties; and multi-level strategies to empower patients and rebuild their bonds to community and larger society. We also call for more empirical research on how non-biomedical healing approaches in various cultural settings could (directly or indirectly) inform HIV cure research.

  16. Preference of Oral Tenofovir Disoproxil Fumarate/Emtricitabine Versus Rectal Tenofovir Reduced-Glycerin 1% Gel Regimens for HIV Prevention Among Cisgender Men and Transgender Women Who Engage in Receptive Anal Intercourse with Men.

    Science.gov (United States)

    Carballo-Diéguez, Alex; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Balán, Iván C; Brown, William; Rael, Christine; Richardson, Barbra A; Piper, Jeanna M; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H; Liu, Albert; Mayer, Kenneth H; Zorrilla, Carmen D; Lama, Javier R; McGowan, Ian; Cranston, Ross D

    2017-12-01

    Oral pre-exposure prophylaxis (PrEP) can prevent HIV transmission. Yet, some may prefer not to take systemic daily medication. MTN-017 was a 3-period, phase 2 safety and acceptability study of microbicide gel applied rectally either daily or before and after receptive anal intercourse (RAI), compared to daily oral tablet. At baseline, cisgender men and transgender women who reported RAI (N = 187) rated the daily oral regimen higher in overall liking, ease of use, and likelihood of future use than the gel regimens. After trying all three, 28% liked daily oral the least. Gel did not affect sexual enjoyment (88%) or improved it (7-8%). Most partners had no reaction to gel use. Ease of gel use improved significantly between the first and the last few times of daily use. A rectal gel used before and after RAI may constitute an attractive alternative to daily tablet. Experience with product use may increase acceptability.

  17. Stabilizing exposure of conserved epitopes by structure guided insertion of disulfide bond in HIV-1 envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Aemro Kassa

    Full Text Available Entry of HIV-1 into target cells requires binding of the viral envelope glycoprotein (Env to cellular receptors and subsequent conformational changes that culminates in fusion of viral and target cell membranes. Recent structural information has revealed that these conformational transitions are regulated by three conserved but potentially flexible layers stacked between the receptor-binding domain (gp120 and the fusion arm (gp41 of Env. We hypothesized that artificial insertion of a covalent bond will 'snap' Env into a conformation that is less mobile and stably expose conserved sites. Therefore, we analyzed the interface between these gp120 layers (layers 1, 2 and 3 and identified residues that may form disulfide bonds when substituted with cysteines. We subsequently probed the structures of the resultant mutant gp120 proteins by assaying their binding to a variety of ligands using Surface Plasmon Resonance (SPR assay. We found that a single disulfide bond strategically inserted between the highly conserved layers 1 and 2 (C65-C115 is able to 'lock' gp120 in a CD4 receptor bound conformation (in the absence of CD4, as indicated by the lower dissociation constant (Kd for the CD4-induced (CD4i epitope binding 17b antibody. When disulfide-stabilized monomeric (gp120 and trimeric (gp140 Envs were used to immunize rabbits, they were found to elicit a higher proportion of antibodies directed against both CD4i and CD4 binding site epitopes than the wild-type proteins. These results demonstrate that structure-guided stabilization of inter-layer interactions within HIV-1 Env can be used to expose conserved epitopes and potentially overcome the sequence diversity of these molecules.

  18. Escape from autologous neutralizing antibodies in acute/early subtype C HIV-1 infection requires multiple pathways.

    Science.gov (United States)

    Rong, Rong; Li, Bing; Lynch, Rebecca M; Haaland, Richard E; Murphy, Megan K; Mulenga, Joseph; Allen, Susan A; Pinter, Abraham; Shaw, George M; Hunter, Eric; Robinson, James E; Gnanakaran, S; Derdeyn, Cynthia A

    2009-09-01

    One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.

  19. The Changes of Positive Selection Within env Gene of HIV-1 B', CRF07_BC and CRF08_BC from China Over Time.

    Science.gov (United States)

    Li, Tingting; Sun, Binlian; Jiang, Yanyan; Zeng, Haiyan; Li, Yanpeng; Wang, Yan; Yang, Rongge

    2017-01-01

    It is not clear about the possible evolutionary changes of the three predominant strains of HIV-1 in China over the course of the epidemic. Envelope (env) gene of HIV-1 is a good target for this evolutionary pressure for its enriched epitopes. We collected 159 full or part of env sequences sampled between 1997 and 2010 from database of China, we calculated the genetic distance, detected the positively selected sites by PAML suite and then compared the number using Fisher's exact test between the early period 1997 to 2003 and the late period 2004 to 2010. We found that the diversity of env genes had increased significantly and the positively selected sites were significantly becoming more over time. V2, V4, and C3 regions had suffered an increase positive selection pressure, while V1, V3, V5 and other conserved regions were relatively stable. Several sites were widely selected and compactly located in C3 and V4, five sites were consecutive in V4.There were two common positively selected sites in all groups: 413T in gp120 and 619L in gp41. The common positively selected sites identified in our study implied that they are important in viral survival and adaptation. Based on the role of V3 region in coreceptor determination and disease progression, our results suggested that the virulence of HIV-1 in China might be stable in the short time span. Given the overall increased tendency of positively selection sites in env, we might predict a less virulent state in the long run. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Cooperative Engagement Capability (CEC)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-582 Cooperative Engagement Capability (CEC) As of FY 2017 President’s Budget Defense...Program Information Program Name Cooperative Engagement Capability (CEC) DoD Component Navy Joint Participants United States Marine Corps; United...dated June 16, 2004 CEC December 2015 SAR March 17, 2016 12:13:59 UNCLASSIFIED 5 Mission and Description Mission The Cooperative Engagement Capability

  1. Constituting Public Engagement

    DEFF Research Database (Denmark)

    Davies, Sarah Rachael

    2013-01-01

    understanding of science to those of public engagement with science and technology (PEST), and the histories, or genealogies, of such models. Data from two qualitative studies-a case study of one of the United Kingdom'ssix Beacons for Public Engagement and a study of contract research staff-are used...... backgrounds, suggesting that multiple and overlapping meanings around PEST are derived from particular histories that have been brought together, through the rubric of public engagement, in assemblages such as the Beacons....

  2. Multiple pathways of escape from HIV broadly cross-neutralizing V2-dependent antibodies.

    Science.gov (United States)

    Moore, Penny L; Sheward, Daniel; Nonyane, Molati; Ranchobe, Nthabeleng; Hermanus, Tandile; Gray, Elin S; Abdool Karim, Salim S; Williamson, Carolyn; Morris, Lynn

    2013-05-01

    Broadly cross-neutralizing (BCN) antibodies are likely to be critical for an effective HIV vaccine. However, the ontogeny of such antibodies and their relationship with autologous viral evolution is unclear. Here, we characterized viral evolution in CAP256, a subtype C-infected individual who developed potent BCN antibodies targeting positions R166 and K169 in the V2 region. CAP256 was superinfected at 3 months postinfection with a virus that was highly sensitive to BCN V2-dependent monoclonal antibodies. The autologous neutralizing response in CAP256 was directed at V1V2, reaching extremely high titers (>1:40,000) against the superinfecting virus at 42 weeks, just 11 weeks prior to the development of the BCN response targeting the same region. Recombination between the primary and superinfecting viruses, especially in V2 and gp41, resulted in two distinct lineages by 4 years postinfection. Although neutralization of some CAP256 clones by plasma from as much as 2 years earlier suggested incomplete viral escape, nonetheless titers against later clones were reduced at least 40-fold to less than 1:1,000. Escape mutations were identified in each lineage, either at R166 or at K169, suggesting that strain-specific and BCN antibodies targeted overlapping epitopes. Furthermore, the early dependence of CAP256 neutralizing antibodies on the N160 glycan decreased with the onset of neutralization breadth, indicating a change in specificity. These data suggest rapid maturation, within 11 weeks, of CAP256 strain-specific antibodies to acquire breadth, with implications for the vaccine elicitation of BCN V2-dependent antibodies. Overall these studies demonstrate that ongoing viral escape is possible, even from BCN antibodies.

  3. Financial incentives to improve progression through the HIV treatment cascade.

    Science.gov (United States)

    Bassett, Ingrid V; Wilson, David; Taaffe, Jessica; Freedberg, Kenneth A

    2015-11-01

    We reviewed recent literature on conditional and unconditional financial incentives for their impact on improving movement through the HIV care cascade and HIV prevention. Concepts from behavioral economics may help improve engagement in HIV care by addressing upstream structural risk factors for HIV, such as poverty, or providing conditional rewards for immediate, measurable outcomes related to HIV care. Incentives have been shown to increase uptake of HIV testing. Yet, few studies to date focus on linkage to care: one large USA-based randomized trial failed to show an effect of incentives; and a smaller trial showed improved linkage to care among drug users, but no difference in virologic suppression. Several small USA-based studies have shown an impact of financial incentives on antiretroviral therapy adherence, but without durability beyond the incentive period. HIV prevention has the most robust evidence for decreasing HIV risk-taking behavior among adolescents and may serve as a model for research on the care cascade. Financial incentives show promise for improving engagement in HIV testing, care, and prevention. Understanding the durability, scalability, ease of implementation, and cost-effectiveness of these different approaches will be critical for maximizing the impact of incentives in curtailing the HIV epidemic.

  4. Randomized Controlled Trial of an Intervention to Maintain Suppression of HIV Viremia After Prison Release: The imPACT Trial.

    Science.gov (United States)

    Wohl, David A; Golin, Carol E; Knight, Kevin; Gould, Michele; Carda-Auten, Jessica; Groves, Jennifer S; Napravnik, Sonia; Cole, Stephen R; White, Becky L; Fogel, Cathie; Rosen, David L; Mugavaro, Michael J; Pence, Brian W; Flynn, Patrick M

    2017-05-01

    HIV-infected individuals transitioning from incarceration to the community are at risk for loss of viral suppression. We compared the effects of imPACT, a multidimensional intervention to promote care engagement after release, to standard care on sustaining viral suppression after community re-entry. This trial randomized 405 HIV-infected inmates being released from prisons in Texas and North Carolina with HIV-1 RNA levels HIV-1 RNA HIV-1 RNA 0.99). Higher rates of HIV suppression and medical care engagement than expected based on previous literature were observed among HIV-infected patients with suppressed viremia released from prison. Randomization to a comprehensive intervention to motivate and facilitate HIV care access after prison release did not prevent loss of viral suppression. A better understanding of the factors influencing prison releasees' linkage to community care, medication adherence, and maintenance of viral suppression is needed to inform policy and other strategic approaches to HIV prevention and treatment.

  5. Impact of HIV testing and counseling (HTC) knowledge on HIV prevention practices among traditional birth attendants in Nigeria.

    Science.gov (United States)

    Osuji, Alice; Pharr, Jennifer R; Nwokoro, Uche; Ike, Anulika; Ali, Christiana; Ejiro, Ogheneaga; Osuyali, John; Obiefune, Michael; Fiscella, Kevin; Ezeanolue, Echezona E

    2015-02-10

    Nigeria is second in the world for the number of people with HIV and has a high rate of mother-to-child transmission (MTCT). Over 60% of births in Nigeria occur outside of health care facilities, and because of this, Traditional Birth Attendants (TBAs) play a significant role in maternal and child health. It is important that TBAs be knowledgeable about HIV prevention. The purpose of this study was to determine the impact of HIV testing and counseling (HTC) knowledge on the HIV prevention practices among TBAs in Nigeria. Five hundred TBAs were surveyed. Chi-square and logistic regression were used to assess differences in HIV prevention practices between TBAs with and without HTC knowledge. TBAs with HTC knowledge are significantly more likely to engage in HIV prevention practices than TBAs without HTC. Prevention practices included: wearing gloves during delivery (p HTC training increases HIV prevention practices and can be a key to improve maternal and child health.

  6. Carbohydrate-binding agents efficiently prevent dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1 transmission to T lymphocytes.

    Science.gov (United States)

    Balzarini, Jan; Van Herrewege, Yven; Vermeire, Kurt; Vanham, Guido; Schols, Dominique

    2007-01-01

    Exposure of HIV-1 to dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-expressing B-lymphoblast Raji cells (Raji/DC-SIGN) but not to wild-type Raji/0 cells results in the capture of HIV-1 particles to the cells as measured by the quantification of cell-associated p24 antigen. Cocultivation of HIV-1-captured Raji/DC-SIGN cells with uninfected CD4+ T lymphocyte C8166 cells results in abundant formation of syncytia within 36 h after cocultivation. Short preexposure of HIV-1 to carbohydrate-binding agents (CBA) dose dependently prevents the Raji/DC-SIGN cells from efficiently binding the virus particles, and no syncytia formation occurs upon subsequent cocultivation with C8166 cells. Thus, the mannose-specific [i.e., the plant lectins Hippeastrum hybrid agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Narcissus pseudonarcissus agglutinin; and Cymbidium agglutinin (CA); the procaryotic cyanovirin-N (CV-N); and the monoclonal antibody 2G12) and N-acetylglucosamine-specific (i.e., the plant lectin Urtica dioica agglutinin) CBAs efficiently abrogate the DC-SIGN-directed HIV-1 capture and subsequent transmission to T lymphocytes. In this assay, the CD4-down-regulating cyclotriazodisulfonamide derivative, the CXCR4 and CCR5 coreceptor antagonists 1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl] - 1,4,8,11 - tetrazacyclotetradecane (AMD3100) and maraviroc, the gp41-binding enfuvirtide, and the polyanionic substances dextran sulfate (M(r) 5000), sulfated polyvinyl alcohol, and the naphthalene sulfonate polymer PRO-2000 were markedly less efficient or even completely ineffective. Similar observations were made in primary monocyte-derived dendritic cell cultures that were infected with HIV-1 particles that had been shortly pre-exposed to the CBAs CV-N, CA, HHA, and GNA and the polyanions DS-5000 and PRO-2000. The potential of CBAs, but not polyanions and other structural/functional classes of entry inhibitors, to impair

  7. "No More Buzz": A Qualitative Study of the Current Response to HIV in the Anglican Church in the Western Cape, South Africa.

    Science.gov (United States)

    Hallonsten, Simon

    2017-08-01

    Using a triangulation design combining participant observation, survey results, and interviews, this paper studies the current form of the response to HIV in the local Anglican Church in the Western Cape, South Africa. The results show that people are generally aware of HIV. The "buzz" around HIV has, however, subsided. The local church does not directly engage HIV anymore, and HIV is more mentioned than talked about. HIV stigma continues to pose a challenge. To work towards the prevention of HIV, the local church needs to put HIV back on the agenda and continue to speak about the virus.

  8. Community-Engaged Scholarship

    DEFF Research Database (Denmark)

    Barinaga, Ester; Parker, Patricia S.

    2013-01-01

    We are pleased to offer this special issue on community-engaged scholarship. As scholar-activists working for social justice alongside youth of color (Pat) and critical arts activists engaging with stigmatized communities (Ester), we began this project with the intent of gathering a collection...

  9. Engagement Means Everyone

    Science.gov (United States)

    Patton, Carol

    2012-01-01

    Employee engagement is not just HR's responsibility. While HR is responsible for the process of measuring and driving engagement, improving it is actually everyone's responsibility. And that means reducing the barriers to productivity to drive business performance. Training departments can play a pivotal role. Their job is to enhance curriculum or…

  10. Experiments in Engagement

    DEFF Research Database (Denmark)

    Selin, Cynthia; Rawlings, Kelly Campbell; Ridder-Vignone, Kathryn de

    2017-01-01

    Public engagement with science and technology is now widely used in science policy and communication. Touted as a means of enhancing democratic discussion of science and technology, analysis of public engagement with science and technology has shown that it is often weakly tied to scientific gove...

  11. The Engagement Gap

    DEFF Research Database (Denmark)

    Tartari, Valentina; Salter, Ammon

    2013-01-01

    Recently, debate on women in academic science has been extended to academics' engagement with industry. We suggest that women tend to engage less in industry collaboration than their male colleagues of similar status. We argue that differences are mitigated by the presence of other women and by s...

  12. On making engagement tangible

    NARCIS (Netherlands)

    van den Broek, Egon; Spink, A.J.; Grieco, F; Krips, O.E.; Loijens, L.W.S.; Noldus, L.P.J.J.; Zimmerman, P.H.

    2012-01-01

    In this article the complexity of the construct engagement and three theories on this topic are discussed. Csikszentmihalyi's theory of flow is taken as starting point for the measurement of engagement. The measurement of each of its eight aspects is discussed, including its pros and cons.

  13. Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140

    Science.gov (United States)

    Go, Eden P.; Herschhorn, Alon; Gu, Christopher; Castillo-Menendez, Luis; Zhang, Shijian; Mao, Youdong; Chen, Haiyan; Ding, Haitao; Wakefield, John K.; Hua, David; Liao, Hua-Xin; Kappes, John C.; Sodroski, Joseph

    2015-01-01

    ABSTRACT The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer, which consists of the gp120 and gp41 subunits, is the focus of multiple strategies for vaccine development. Extensive Env glycosylation provides HIV-1 with protection from the immune system, yet the glycans are also essential components of binding epitopes for numerous broadly neutralizing antibodies. Recent studies have shown that when Env is isolated from virions, its glycosylation profile differs significantly from that of soluble forms of Env (gp120 or gp140) predominantly used in vaccine discovery research. Here we show that exogenous membrane-anchored Envs, which can be produced in large quantities in mammalian cells, also display a virion-like glycan profile, where the glycoprotein is extensively decorated with high-mannose glycans. Additionally, because we characterized the glycosylation with a high-fidelity profiling method, glycopeptide analysis, an unprecedented level of molecular detail regarding membrane Env glycosylation and its heterogeneity is presented. Each glycosylation site was characterized individually, with about 500 glycoforms characterized per Env protein. While many of the sites contain exclusively high-mannose glycans, others retain complex glycans, resulting in a glycan profile that cannot currently be mimicked on soluble gp120 or gp140 preparations. These site-level studies are important for understanding antibody-glycan interactions on native Env trimers. Additionally, we report a newly observed O-linked glycosylation site, T606, and we show that the full O-linked glycosylation profile of membrane-associated Env is similar to that of soluble gp140. These findings provide new insight into Env glycosylation and clarify key molecular-level differences between membrane-anchored Env and soluble gp140. IMPORTANCE A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface

  14. V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Meg M Laakso

    2007-08-01

    Full Text Available The V1/V2 region and the V3 loop of the human immunodeficiency virus type I (HIV-1 envelope (Env protein are targets for neutralizing antibodies and also play an important functional role, with the V3 loop largely determining whether a virus uses CCR5 (R5, CXCR4 (X4, or either coreceptor (R5X4 to infect cells. While the sequence of V3 is variable, its length is highly conserved. Structural studies indicate that V3 length may be important for interactions with the extracellular loops of the coreceptor. Consistent with this view, genetic truncation of the V3 loop is typically associated with loss of Env function. We removed approximately one-half of the V3 loop from three different HIV-1 strains, and found that only the Env protein from the R5X4 strain R3A retained some fusion activity. Loss of V1/V2 (DeltaV1/V2 was well tolerated by this virus. Passaging of virus with the truncated V3 loop resulted in the derivation of a virus strain that replicated with wild-type kinetics. This virus, termed TA1, retained the V3 loop truncation and acquired several adaptive changes in gp120 and gp41. TA1 could use CCR5 but not CXCR4 to infect cells, and was extremely sensitive to neutralization by HIV-1 positive human sera, and by antibodies to the CD4 binding site and to CD4-induced epitopes in the bridging sheet region of gp120. In addition, TA1 was completely resistant to CCR5 inhibitors, and was more dependent upon the N-terminal domain of CCR5, a region of the receptor that is thought to contact the bridging sheet of gp120 and the base of the V3 loop, and whose conformation may not be greatly affected by CCR5 inhibitors. These studies suggest that the V3 loop protects HIV from neutralization by antibodies prevalent in infected humans, that CCR5 inhibitors likely act by disrupting interactions between the V3 loop and the coreceptor, and that altered use of CCR5 by HIV-1 associated with increased sensitivity to changes in the N-terminal domain can be linked

  15. Get Tested for HIV

    Science.gov (United States)

    ... The Basics: What Is HIV? What is HIV? HIV stands for human immunodeficiency virus. This is the virus that causes AIDS. There is no cure yet for HIV/AIDS, but there are treatments that can help ...

  16. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... that may be present in rare strains of HIV. The test may not detect a drug-resistant strain of ... Less Common Questions Related Content On This Site Tests: HIV Viral Load ; CD4 Count ; HIV Antibody and HIV ...

  17. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV ... antiretroviral drugs. With genotypic resistance testing, the genetic code of the HIV a person has been infected ...

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. HIV and Rheumatic Disease

    Science.gov (United States)

    ... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  3. 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: January 18, 2018 ...

  4. 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 ( ...

  5. HIV/AIDS Coinfection

    Science.gov (United States)

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

  6. [HIV lipodystrophy].

    Science.gov (United States)

    Snopková, S; Matýsková, M; Povolná, K; Polák, P; Husa, P

    2010-12-01

    Combined antiretroviral therapy results in extraordinary decrease of morbidity and mortality of HIV-infected patients and in an essential change of the HIV/AIDS disease prognosis. However, long-term intake of antiretroviral medicaments is related to occurrence of metabolic and morphological abnormalities, of which some have been combined into a new syndrome--the so called HIV lipodystrophy. The HIV lipodystrophy syndrome covers metabolic and morphological changes. Metabolic changes include dyslipidaemia with hypercholesterolaemia and/or hypertriglyceridaemia, insulin resistance with hyperinsulinaemia and hyperlaktataemia. Morphological changes have the nature of lipoatrophia (loss of subcutaneous fat--on the cheeks, on extremities, on buttocks and marked prominence of surface veins) or lipohypertrophia (growth of fat tissue--on the chest, in the dorsocervical area, lipomatosis of visceral tissues and organs, fat accumulation in the abdominal area). Several HIV lipodystrophy features are very similar to the metabolic syndrome of the general population. That is why this new syndrome represents a prospective risk of premature atherosclerosis and increase of the cardiovascular risk in young HIV positive individuals. The article mentions major presented studies dealing with the relation of antiretroviral treatment and the cardiovascular risk. The conclusions of the studies are not unequivocal--this is, among others, given by the reason that their length is short from the viewpoint of atherogenesis. The major risk of subclinical atherosclerosis acceleration seems to be related to the deep immunodeficiency and low number of CD4+ lymphocytes and florid, uncontrolled HIV infection with a high number of HIV-1 RNA copies actually circulating in the plasma. The question, whether metabolic and morphological changes related to HIV and cART carry a similar atherogenic potential as in the general population, remains open for future.

  7. Evaluation of HIV testing recommendations in specialty guidelines for the management of HIV indicator conditions.

    Science.gov (United States)

    Lord, E; Stockdale, A J; Malek, R; Rae, C; Sperle, I; Raben, D; Freedman, A; Churchill, D; Lundgren, J; Sullivan, A K

    2017-04-01

    European guidelines recommend HIV testing for individuals presenting with indicator conditions (ICs) including AIDS-defining conditions (ADCs). The extent to which non-HIV specialty guidelines recommend HIV testing in ICs and ADCs is unknown. Our aim was to pilot a methodology in the UK to review specialty guidelines and ascertain if HIV was discussed and testing recommended. UK and European HIV testing guidelines were reviewed to produce a list of 25 ADCs and 49 ICs. UK guidelines for these conditions were identified from searches of the websites of specialist societies, the National Institute of Clinical Excellence (NICE) website, the NICE Clinical Knowledge Summaries (CKS) website, the Scottish Intercollegiate Guidance Network (SIGN) website and the British Medical Journal Best Practice database and from Google searches. We identified guidelines for 12 of 25 ADCs (48%) and 36 of 49 (73%) ICs. In total, 78 guidelines were reviewed (range 0-13 per condition). HIV testing was recommended in six of 17 ADC guidelines (35%) and 24 of 61 IC guidelines (39%). At least one guideline recommended HIV testing for six of 25 ADCs (24%) and 16 of 49 ICs (33%). There was no association between recommendation to test and publication year (P = 0.62). The majority of guidelines for ICs do not recommend testing. Clinicians managing ICs may be unaware of recommendations produced by HIV societies or the prevalence of undiagnosed HIV infection among these patients. We are piloting methods to engage with guideline development groups to ensure that patients diagnosed with ICs/ADCs are tested for HIV. We then plan to apply our methodology in other European settings as part of the Optimising Testing and Linkage to Care for HIV across Europe (OptTEST) project. © 2016 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  8. Dating, marriage, and parenthood for HIV-positive heterosexual Puerto Rican men: normalizing perspectives on everyday life with HIV.

    Science.gov (United States)

    Sastre, Francisco; Sheehan, Diana M; Gonzalez, Arnaldo

    2015-03-01

    HIV-positive men are living long and healthier lives while managing HIV as a chronic illness. Although research has extensively documented the experiences of illness of people living with HIV, dating, marriage, and fatherhood among heterosexual Latino men has not been examined. To address this gap, this study used a qualitative study design to examine patterns and strategies for dating, marriage, and parenthood among 24 HIV-positive heterosexual Puerto Rican men living in Boston. The findings in our study indicate that an HIV diagnosis does not necessarily deter men from having an active sexual life, marrying, or having children. In fact, for some of the men, engaging in these social and life-changing events is part of moving on and normalizing life with HIV; these men planned for, achieved, and interpreted these events in the context of establishing normalcy with HIV. Although the HIV diagnosis discouraged some men from engaging in sexual relations, getting married, or having children, others fulfilled these desires with strategies aimed to reconciling their HIV status in their personal life, including dating or marrying HIV-positive women only. Additional important themes identified in this study include the decision to disclose HIV status to new sexual partners as well as the decision to accept the risk of HIV transmission to a child or partner in order to fulfill desires of fatherhood. Understanding the personal struggles, decision-making patterns, and needs of HIV-positive heterosexual men can aid in designing interventions that support healthy living with HIV. © The Author(s) 2014.

  9. 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. What Is HIV? ( http://www.cdc.gov/hiv/pubs/faq/faq1.htm ). ...

  10. Stigma, activism, and well-being among people living with HIV.

    Science.gov (United States)

    Earnshaw, Valerie A; Rosenthal, Lisa; Lang, Shawn M

    2016-01-01

    Evidence demonstrates that HIV stigma undermines the psychological and physical health of people living with HIV (PLWH). Yet, PLWH describe engaging in HIV activism to challenge stigma, and research suggests that individuals may benefit from activism. We examine associations between experiences of HIV stigma and HIV activism, and test whether HIV activists benefit from greater well-being than non-activists. Participants include 93 PLWH recruited from drop-in centers, housing programs, and other organizations providing services to PLWH in the Northeastern USA between 2012 and 2013 (mean age = 50 years; 56% Black, 20% White, 18% Other; 61% non-Latino(a), 39% Latino(a); 59% male, 38% female, 3% transgender; 82% heterosexual, 15% sexual minority). Participants completed a cross-sectional written survey. Results of regression analyses suggest that PLWH who experienced greater enacted stigma engaged in greater HIV activism. Anticipated, internalized, and perceived public stigma, however, were unrelated to HIV activism. Moreover, results of a multivariate analysis of variance suggest that HIV activists reported greater social network integration, greater social well-being, greater engagement in active coping with discrimination, and greater meaning in life than non-activists. Yet, HIV activists also reported somewhat greater depressive symptoms than non-activists, suggesting that the association between HIV activism and well-being is complex. By differentiating between HIV stigma mechanisms, the current study provides a more nuanced understanding of which experiences of HIV stigma may be associated with HIV activism. It further suggests that engagement in activism may offer benefits to PLWH, while raising the possibility that activists could experience greater depressive symptoms than non-activists. Given the preliminary nature of this study, future research should continue to examine these complex associations between HIV stigma, activism, and well-being among PLWH

  11. HIV Among Asians

    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 Among Asians in the United States Format: Select ...

  12. 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 ...

  13. HIV among Transgender People

    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 Among Transgender People Format: Select One PDF [227K] ...

  14. Epidemiology of infections with intestinal parasites and human immunodeficiency virus (HIV) among sugar-estate residents in Ethiopia

    NARCIS (Netherlands)

    Fontanet, A. L.; Sahlu, T.; Rinke de Wit, T.; Messele, T.; Masho, W.; Woldemichael, T.; Yeneneh, H.; Coutinho, R. A.

    2000-01-01

    Intestinal parasitic infections could play an important role in the progression of infection with human immunodeficiency virus (HIV), by further disturbing the immune system whilst it is already engaged in the fight against HIV. HIV and intestinal parasitic infections were investigated in 1239,

  15. Project Roadmap: Reeducating Older Adults in Maintaining AIDS Prevention--A Secondary Intervention for Older HIV-Positive Adults

    Science.gov (United States)

    Illa, Lourdes; Echenique, Marisa; Saint Jean, Gilbert; Bustamante-Avellaneda, Victoria; Metsch, Lisa; Mendez-Mulet, Luis; Eisdorfer, Carl; Sanchez-Martinez, Mario

    2010-01-01

    The number of older adults living with HIV/AIDS is larger than ever. Little is known about their sexual behaviors, although contrary to stereotypes, older adults desire and engage in sexual activity. Despite increased recognition of the need for prevention interventions targeting HIV-positive individuals, no secondary HIV prevention interventions…

  16. Mental Health Pathways from Interpersonal Violence to Health-Related Outcomes in HIV-Positive Sexual Minority Men

    Science.gov (United States)

    Pantalone, David W.; Hessler, Danielle M.; Simoni, Jane M.

    2010-01-01

    Objective: We examined mental health pathways between interpersonal violence (IPV) and health-related outcomes in HIV-positive sexual minority men engaged with medical care. Method: HIV-positive gay and bisexual men (N = 178) were recruited for this cross-sectional study from 2 public HIV primary care clinics that treated outpatients in an urban…

  17. The ABCs of Student Engagement

    Science.gov (United States)

    Parsons, Seth A.; Nuland, Leila Richey; Parsons, Allison Ward

    2014-01-01

    Student engagement is an important consideration for teachers and administrators because it is explicitly associated with achievement. What the authors call the ABC's of engagement they outline as: Affective engagement, Behavioral engagement, and Cognitive engagement. They also present "Three Things Every Teacher Needs to Know about…

  18. Measuring user engagement

    CERN Document Server

    Lalmas, Mounia; Yom-Tov, Elad

    2014-01-01

    User engagement refers to the quality of the user experience that emphasizes the positive aspects of interacting with an online application and, in particular, the desire to use that application longer and repeatedly. User engagement is a key concept in the design of online applications (whether for desktop, tablet or mobile), motivated by the observation that successful applications are not just used, but are engaged with. Users invest time, attention, and emotion in their use of technology, and seek to satisfy pragmatic and hedonic needs. Measurement is critical for evaluating whether online

  19. The Player Engagement Process

    DEFF Research Database (Denmark)

    Schoenau-Fog, Henrik

    2011-01-01

    Engagement is an essential element of the player experience, and the concept is described in various ways in the literature. To gain a more detailed comprehension of this multifaceted concept, and in order to better understand what aspects can be used to evaluate engaging game play and to design......, categories and triggers involved in this process. By applying grounded theory to the analysis of the responses, a process-oriented player engagement framework was developed and four main components consisting of objectives, activities, accomplishments and affects as well as the corresponding categories...

  20. Closing the RN engagement gap: which drivers of engagement matter?

    Science.gov (United States)

    Rivera, Reynaldo R; Fitzpatrick, Joyce J; Boyle, Suzanne M

    2011-06-01

    This study focused on the relationship between RNs' perceptions of drivers of engagement and their workplace engagement. In multiple studies, mostly not in healthcare, researchers found that employees engaged in their work are in the minority. This phenomenon is referred to as the engagement gap. Drivers of engagement and levels of nurse engagement were measured among 510 RNs from a large urban academic university center. The greatest difference between engaged and not-engaged nurses was in the manager action index; the smallest difference was in the salary and benefits index. The passion-for-nursing index was the only significant driver related to RN levels of engagement when controlling for all the other drivers. Nurse managers play a critical role in promoting employee engagement. The nurses' passion for nursing is an important dimension of engagement. Salary and benefits were not primary drivers in employee engagement. Copyright © 2011 Wolters Kluwer Health Lippincott Williams & Wilkins

  1. Circumcision of male children for reduction of future risk for HIV: acceptability among HIV serodiscordant couples in Kampala, Uganda.

    Directory of Open Access Journals (Sweden)

    Kenneth K Mugwanya

    Full Text Available The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14 and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07 were significantly (p≤0.05 more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004 and those who were HIV seropositive (APR 1.09, p = 0.03 were also more likely to be interested in child circumcision for HIV prevention.A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention.

  2. Effects of mortality salience and perceived vulnerability on HIV testing intentions and behaviour.

    Science.gov (United States)

    Grover, Kristin W; Miller, Carol T

    2014-01-01

    Research indicates that death thoughts that occur in response to health threats affect subsequent health behaviour. The present study examined the effects of mortality salience on HIV testing. After reading an article that was intended to make them perceive that they had high or low vulnerability to HIV, participants wrote about death or an aversive control topic. Participants then indicated their intentions to get tested for HIV and were given the opportunity to take an HIV test at the end of the study. Results showed that mortality salience increased testing behaviour among participants who were made to feel vulnerable to HIV, but decreased testing behaviour among participants who were not made to feel vulnerable to HIV infection. This research suggests that HIV prevention programmes must carefully consider how the association many people make between HIV and death may interact with people's perceptions of their vulnerability to HIV infection to affect their willingness to engage in preventative behaviours.

  3. Sexual Behavior as a Function of Stigma and Coping with Stigma Among People with HIV/AIDS in Rural New England

    OpenAIRE

    Varni, Susan E.; Miller, Carol T.; Solomon, Sondra E.

    2012-01-01

    The relationship between coping with HIV/AIDS stigma and engaging in risky sexual behavior (i.e., inconsistent condom use) was examined in HIV-positive adults living in rural areas. Participants answered questions about their experiences with HIV/AIDS prejudice and discrimination (enacted stigma) and their perceptions of felt HIV/AIDS stigma (disclosure concerns, negative self-image, and concern with public attitudes). They were also asked about how they coped with HIV/AIDS stigma, and about ...

  4. Racial/ethnic differences in the rates and correlates of HIV risk behaviors among drug abusers.

    Science.gov (United States)

    Brooks, Audrey J; Lokhnygina, Yuliya; Meade, Christina S; Potter, Jennifer Sharpe; Calsyn, Donald A; Greenfield, Shelly F

    2013-01-01

    HIV infection disproportionately impacts minorities; yet research on racial/ethnic differences in the prevalence and correlates of HIV risk behaviors is limited. This study examined racial/ethnic differences in the rates of HIV risk behaviors and whether the relationship between HIV risk factors and HIV risk behaviors varies by race/ethnicity in clients participating in NIDA Clinical Trials Network trials. The sample was 41% non-Hispanic White, 32% non-Hispanic Black, and 27% Hispanic (N = 2,063). HIV risk behaviors and measures of substance and psychosocial HIV risk factors in the past month were obtained. Non-Hispanic Blacks engaged in less HIV sexual risk behaviors overall than non-Hispanic Whites. While non-Hispanic Whites were the most likely to report any injection drug use, Hispanics engaged in the most HIV drug risk behaviors. Specific risk factors were differentially predictive of HIV risk behavior by race/ethnicity. Alcohol use severity was related to engaging in higher sex risk behaviors for non-Hispanic Blacks and Whites. Greater psychiatric severity was related to engaging in higher sex risk behaviors for non-Hispanic Whites. Drug use severity was associated with engaging in higher risk drug behaviors for non-Hispanic Whites and Hispanics with the magnitude of the relationship stronger for Hispanics. These findings highlight the need for further research testing HIV risk prevention interventions within racial/ethnic groups to identify target behaviors or risk factors that are salient to inform HIV interventions. The present study provides a systematic examination of race/ethnicity differences in the relationship between psychosocial risk factors and HIV risk behaviors. Copyright © American Academy of Addiction Psychiatry.

  5. Cohabitation and social engagement

    Directory of Open Access Journals (Sweden)

    Christoph M. Schimmele

    2011-01-01

    Full Text Available In Canada, nonmarital cohabitation has become a normative life experience, but there are uncertainties regarding its contribution to social cohesion. This article compares and contrasts cohabitation with marriage (and other marital statuses on two dimensions of social engagement:social networks and prosocial behaviour. The study employs GSS-17 microdata and logistic regression analysis. The findings illustrate that social engagement is similar among cohabitors and the married.

  6. Cohabitation and social engagement

    OpenAIRE

    Christoph M. Schimmele; Zheng Wu

    2012-01-01

    In Canada, nonmarital cohabitation has become a normative life experience, but there are uncertainties regarding its contribution to social cohesion. This article compares and contrasts cohabitation with marriage (and other marital statuses) on two dimensions of social engagement:social networks and prosocial behaviour. The study employs GSS-17 microdata and logistic regression analysis. The findings illustrate that social engagement is similar among cohabitors and the married.

  7. Cohabitation and social engagement

    Directory of Open Access Journals (Sweden)

    Christoph M. Schimmele

    2012-07-01

    Full Text Available In Canada, nonmarital cohabitation has become a normative life experience, but there are uncertainties regarding its contribution to social cohesion. This article compares and contrasts cohabitation with marriage (and other marital statuses on two dimensions of social engagement:social networks and prosocial behaviour. The study employs GSS-17 microdata and logistic regression analysis. The findings illustrate that social engagement is similar among cohabitors and the married.

  8. The rules of engagement

    DEFF Research Database (Denmark)

    Davies, Sarah Rachael

    2013-01-01

    this framework I argue that we can understand public engagement events as hallmarked by conflict, but that this conflict emerges not in differing assessments of the value of different forms of knowledge but around the very form of a dialogue event; similarly, I suggest that the content of talk indicates...... that imposed hierarchies are continually re-negotiated. In concluding I reflect on some implications of using power in the analysis of engagement....

  9. A descriptive analysis of perceptions of HIV risk and worry about acquiring HIV among FEM-PrEP participants who seroconverted in Bondo, Kenya, and Pretoria, South Africa

    Directory of Open Access Journals (Sweden)

    Amy L Corneli

    2014-09-01

    Full Text Available Introduction: Risk perception is a core construct in many behaviour change theories in public health. Individuals who believe they are at risk of acquiring an illness may be more likely to engage in behaviours to reduce that risk; those who do not feel at risk may be unlikely to engage in risk reduction behaviours. Among participants who seroconverted in two FEM-PrEP sites – Bondo, Kenya, and Pretoria, South Africa – we explored perceived HIV risk and worry about acquiring HIV prior to HIV infection. Methods: FEM-PrEP was a phase III clinical trial of once-daily, oral emtricitabine and tenofovir disoproxil fumarate for HIV prevention among women in sub-Saharan Africa. We asked all participants about their perceived HIV risk in the next four weeks, prior to HIV testing, during a quantitative face-to-face interview at enrolment and at quarterly follow-up visits. Among participants who seroconverted, we calculated the frequencies of their responses from the visit conducted closest to, but before, HIV acquisition. Also among women who seroconverted, we conducted qualitative, semi-structured interviews (SSIs at weeks 1, 4 and 8 after participants’ HIV diagnosis visit to retrospectively explore feelings of HIV worry. Applied thematic analysis was used to analyse the SSI data. Results: Among participants who seroconverted in Bondo and Pretoria, 52% reported in the quantitative interview that they had no chance of acquiring HIV in the next four weeks. We identified four processes of risk rationalization from the SSI narratives. In “protective behaviour,” participants described at least one risk reduction behaviour they used to reduce their HIV risk; these actions made them feel not vulnerable to HIV, and therefore they did not worry about acquiring the virus. In “protective reasoning,” participants considered their HIV risk but rationalized, based on certain events or beliefs, that they were not vulnerable and therefore did not worry about

  10. Humoral Immunogenicity of an HIV-1 Envelope Residue 649-684 Membrane-proximal Region Peptide Fused to the Plague Antigen F1-V

    Science.gov (United States)

    Matoba, Nobuyuki; Shah, Namrata Rahul; Mor, Tsafrir S

    2011-01-01

    The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR649-684 (F1-V-MPR649-684). We employed systemic immunization for initial feasibility analyses. Despite strong immunogenicity demonstrated for the immunogen, repeated systemic immunizations of mice with F1-V-MPR649-684 hardly induced MPR649-684-specific IgG. In contrast, a single immunization with F1-V-MPR649-684 mounted a significant anti-MPR649-684 IgG response in animals that were primed with another MPR649-684 fusion protein based on the cholera toxin B subunit. Additional boost immunizations with F1-V-MPR649-684 recalled and maintained the antibody response and expanded the number of specific antibody-secreting B cells. Thus, while F1-V-MPR649-684 alone was not sufficiently immunogenic to induce detectable levels of MPR649-684-specific antibodies, these results suggest that prime-boost immunization using heterologous antigen-display platforms may overcome the poor humoral immunogenicity of MPR649-684 for the induction of durable humoral immunity. Further studies are warranted to evaluate the feasibility of this strategy in mucosal immunization. Lastly, our findings add to a growing body of evidence in support of this strategy for immunogen design for poorly immunogenic epitopes besides the MPR of HIV-1's transmembrane envelope protein. PMID:21693158

  11. 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.

  12. Acute Alcohol Consumption Directly Increases HIV Transmission Risk: A Randomized Controlled Experiment.

    Science.gov (United States)

    Shuper, Paul A; Joharchi, Narges; Monti, Peter M; Loutfy, Mona; Rehm, Jürgen

    2017-12-15

    Alcohol consumption has frequently been purported as a driver of condomless sex and HIV transmission, but to date, experimental evidence for the causal risk-taking impact of alcohol among HIV-positive populations is lacking. The present experiment sought to determine whether acute alcohol consumption has a direct causal impact on condomless sex intentions among HIV-positive men-who-have-sex-with-men (MSM), and to assess whether alcohol's impact differs between MSM who are HIV-positive versus HIV-negative. In a randomized controlled alcohol administration experiment, HIV-positive and HIV-negative MSM were brought into a specialized barroom laboratory and randomly assigned to beverage consumption condition: alcohol (target blood alcohol concentration = 0.080%), placebo alcohol (target blood alcohol concentration = 0.000%), or water (control). Participants then underwent a video-based sexual arousal manipulation (sexually aroused/nonaroused) and indicated their intentions to engage in condom-protected and condomless sexual acts in a standardized paradigm. The primary outcome entailed intentions to engage in condomless receptive and condomless insertive anal sex. A total of 282 MSM (141 HIV-positive; 141 HIV-negative) completed experimental procedures. MSM who received alcohol reported significantly stronger intentions to engage in condomless sex than those who received placebo alcohol or water (F(1,274) = 9.43, P = 0.002). The impact of alcohol did not differ between HIV-positive and HIV-negative MSM (F(1,274) = 1.86, P = 0.174). The present investigation entailed the first risk-focused alcohol administration experiment to involve an HIV-positive sample, and results demonstrated that consuming alcohol had an independent, causal impact on intentions to engage in sexual behaviors that can result in HIV transmission. Findings strongly suggest that alcohol-focused initiatives should be incorporated into HIV prevention efforts.

  13. Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity hinder elicitation of the anti-HIV antibody 4E10.

    Directory of Open Access Journals (Sweden)

    Kathryn A K Finton

    Full Text Available The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of the HIV envelope protein gp41. Previous attempts to elicit 4E10 by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that the ontogeny of 4E10-equivalent responses was blocked by inherent autoreactivity and exceptional polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent with recognition of autoantigen/s by 4E10 and the presumption that tolerance mechanisms may hinder the elicitation of 4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly to cardiolipin-containing liposomes, but also bound negatively-charged, non-cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was predominantly mediated by electrostatic interactions rather than presumed hydrophobic interactions. The crystal structure of 4E10 free of bound ligands showed a dramatic restructuring of the combining site, occluding the HIV epitope binding site and revealing profound flexibility, but creating an electropositive pocket consistent with non-specific binding of phospholipid headgroups. These results strongly suggested that antigens other than cardiolipin mediate 4E10 autoreactivity. Using a synthetic peptide library spanning the human proteome, we determined that 4E10 displays limited and focused, but unexceptional, polyspecificity. We also identified a novel autoepitope shared by three ER-resident inositol trisphosphate receptors, validated through binding studies and immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity consistent with the type 1 inositol trisphosphate receptor as the most likely candidate autoantigen, but is inconsistent with

  14. Improving the Expression and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers by Targeted Sequence Changes.

    Science.gov (United States)

    Ringe, Rajesh P; Ozorowski, Gabriel; Yasmeen, Anila; Cupo, Albert; Cruz Portillo, Victor M; Pugach, Pavel; Golabek, Michael; Rantalainen, Kimmo; Holden, Lauren G; Cottrell, Christopher A; Wilson, Ian A; Sanders, Rogier W; Ward, Andrew B; Klasse, P J; Moore, John P

    2017-06-15

    Soluble, recombinant native-like envelope glycoprotein (Env) trimers of various human immunodeficiency virus type 1 (HIV-1) genotypes are being developed for structural studies and as vaccine candidates aimed at the induction of broadly neutralizing antibodies (bNAbs). The prototypic design is designated SOSIP.664, but many HIV-1 env genes do not yield fully native-like trimers efficiently. One such env gene is CZA97.012 from a neutralization-resistant (tier 2) clade C virus. As appropriately purified, native-like CZA97.012 SOSIP.664 trimers induce autologous neutralizing antibodies (NAbs) efficiently in immunized rabbits, we sought to improve the efficiency with which they can be produced and to better understand the limitations to the original design. By using structure- and antigenicity-guided mutagenesis strategies focused on the V2 and V3 regions and the gp120-gp41 interface, we developed the CZA97 SOSIP.v4.2-M6.IT construct. Fully native-like, stable trimers that display multiple bNAb epitopes could be expressed from this construct in a stable CHO cell line and purified at an acceptable yield using either a PGT145 or a 2G12 bNAb affinity column. We also show that similar mutagenesis strategies can be used to improve the yields and properties of SOSIP.664 trimers of the DU422, 426c, and 92UG037 genotypes.IMPORTANCE Recombinant trimeric proteins based on HIV-1 env genes are being developed for future vaccine trials in humans. A feature of these proteins is their mimicry of the envelope glycoprotein (Env) structure on virus particles that is targeted by neutralizing antibodies, i.e., antibodies that prevent cells from becoming infected. The vaccine concept under exploration is that recombinant trimers may be able to elicit virus-neutralizing antibodies when delivered as immunogens. Because HIV-1 is extremely variable, a practical vaccine may need to incorporate Env trimers derived from multiple different virus sequences. Accordingly, we need to understand how to

  15. Medarbejderinvolvering og engagement i arbejdspladsvurdering

    DEFF Research Database (Denmark)

    Hasle, Peter; Thoft, Eva

    2000-01-01

    En vurdering af betingelserne for at udvikle medarbejder involvering og engagement i arbejdspladsvurdering.......En vurdering af betingelserne for at udvikle medarbejder involvering og engagement i arbejdspladsvurdering....

  16. 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

  17. Engaging male partners in women's microbicide use: evidence from clinical trials and implications for future research and microbicide introduction

    NARCIS (Netherlands)

    Lanham, M.; Wilcher, R.; Montgomery, E.T.; Pool, R.; Schuler, S.; Lenzi, R.; Friedland, B.

    2014-01-01

    Introduction: Constructively engaging male partners in women-centred health programs such as family planning and prevention of mother-to-child HIV transmission has resulted in both improved health outcomes and stronger relationships. Concerted efforts to engage men in microbicide use could make it

  18. The Engagement Gap

    DEFF Research Database (Denmark)

    Tartari, Valentina; Salter, Ammon

    2015-01-01

    In recent years, the debate about the marginality of women in academic science has been extended to academics’ engagement with industry and their commercial efforts. Analyzing multi-source data for a large sample of UK physical and engineering scientists and employing a matching technique......, this study suggests women academics to engage less and in different ways than their male colleagues of similar status in collaboration activities with industry. We then argue – and empirical assess – these differences can be mitigated by the social context in which women scientists operate, including...... the presence of women in the local work setting and their wider discipline, and the institutional support for women’s careers in their organization. We explore the implications of these findings for policies to support women’s scientific and technical careers and engagement with industry....

  19. Engagement beyond critique?

    DEFF Research Database (Denmark)

    Nielsen, Gritt B.; Jørgensen, Nanna Jordt

    2018-01-01

    on anthropological engagement: policy-oriented activist research, feminist inspired collaborative research, and what we have chosen to call research for alterity and alternatives. Each of these approaches engage with the concepts of community and participation, two terms which require cautiousness and critical......In response to academic ideals of neutrality, complexity and cultural relativism promoted in postmodern cultural critique, different attempts have been made to make anthropology more “engaged” in the promotion of social change. In this article, we discuss three contemporary positions...... scrutiny, we argue. While each approach to anthropological engagement is valuable in its own right, their application requires careful consideration and knowledge about the contemporary political climate, which in many places is characterized by growing segregation and antagonism between different groups...

  20. Engagement and Education

    Science.gov (United States)

    Tosh, Pritish K.; Hick, John L.; Hanfling, Dan; Geiling, James; Reed, Mary Jane; Uyeki, Timothy M.; Shah, Umair A.; Fagbuyi, Daniel B.; Skippen, Peter; Dichter, Jeffrey R.; Kissoon, Niranjan; Christian, Michael D.; Upperman, Jeffrey S.; Christian, Michael D.; Devereaux, Asha V.; Dichter, Jeffrey R.; Kissoon, Niranjan; Rubinson, Lewis; Amundson, Dennis; Anderson, Michael R.; Balk, Robert; Barfield, Wanda D.; Bartz, Martha; Benditt, Josh; Beninati, William; Berkowitz, Kenneth A.; Daugherty Biddison, Lee; Braner, Dana; Branson, Richard D; Burkle, Frederick M.; Cairns, Bruce A.; Carr, Brendan G.; Courtney, Brooke; DeDecker, Lisa D.; De Jong, Marla J.; Dominguez-Cherit, Guillermo; Dries, David; Einav, Sharon; Erstad, Brian L.; Etienne, Mill; Fagbuyi, Daniel B.; Fang, Ray; Feldman, Henry; Garzon, Hernando; Geiling, James; Gomersall, Charles D.; Grissom, Colin K.; Hanfling, Dan; Hick, John L.; Hodge, James G.; Hupert, Nathaniel; Ingbar, David; Kanter, Robert K.; King, Mary A.; Kuhnley, Robert N.; Lawler, James; Leung, Sharon; Levy, Deborah A.; Lim, Matthew L.; Livinski, Alicia; Luyckx, Valerie; Marcozzi, David; Medina, Justine; Miramontes, David A.; Mutter, Ryan; Niven, Alexander S.; Penn, Matthew S.; Pepe, Paul E.; Powell, Tia; Prezant, David; Reed, Mary Jane; Rich, Preston; Rodriquez, Dario; Roxland, Beth E.; Sarani, Babak; Shah, Umair A.; Skippen, Peter; Sprung, Charles L.; Subbarao, Italo; Talmor, Daniel; Toner, Eric S.; Tosh, Pritish K.; Upperman, Jeffrey S.; Uyeki, Timothy M.; Weireter, Leonard J.; West, T. Eoin; Wilgis, John; Ornelas, Joe; McBride, Deborah; Reid, David; Baez, Amado; Baldisseri, Marie; Blumenstock, James S.; Cooper, Art; Ellender, Tim; Helminiak, Clare; Jimenez, Edgar; Krug, Steve; Lamana, Joe; Masur, Henry; Mathivha, L. Rudo; Osterholm, Michael T.; Reynolds, H. Neal; Sandrock, Christian; Sprecher, Armand; Tillyard, Andrew; White, Douglas; Wise, Robert; Yeskey, Kevin

    2014-01-01

    BACKGROUND: Engagement and education of ICU clinicians in disaster preparedness is fragmented by time constraints and institutional barriers and frequently occurs during a disaster. We reviewed the existing literature from 2007 to April 2013 and expert opinions about clinician engagement and education for critical care during a pandemic or disaster and offer suggestions for integrating ICU clinicians into planning and response. The suggestions in this article are important for all of those involved in a pandemic or large-scale disaster with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government officials. METHODS: A systematic literature review was performed and suggestions formulated according to the American College of Chest Physicians (CHEST) Consensus Statement development methodology. We assessed articles, documents, reports, and gray literature reported since 2007. Following expert-informed sorting and review of the literature, key priority areas and questions were developed. No studies of sufficient quality were identified upon which to make evidence-based recommendations. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process. RESULTS: Twenty-three suggestions were formulated based on literature-informed consensus opinion. These suggestions are grouped according to the following thematic elements: (1) situational awareness, (2) clinician roles and responsibilities, (3) education, and (4) community engagement. Together, these four elements are considered to form the basis for effective ICU clinician engagement for mass critical care. CONCLUSIONS: The optimal engagement of the ICU clinical team in caring for large numbers of critically ill patients due to a pandemic or disaster will require a departure from the routine independent systems operating in hospitals. An effective response will require robust information systems; coordination

  1. Public Engagement with Science

    DEFF Research Database (Denmark)

    Irwin, Alan

    2014-01-01

    not problematising ‘the public’, taking values seriously and instead educating ‘the experts’, and recognising both the ‘legitimacy of wider concerns’ and the ‘democratic imperative’. Public Engagement with Science as strategy is building upon a normative commitment to the idea of democratic science policy...... for dialogue exercises look microscopic against the backdrop of global science and its governance. Maybe it has been over-promised what such public engagement exercises can deliver. We can safely conclude that, despite all the ‘from deficit to democracy’ talk, no such easy shift has been made. At best, partial...

  2. Science, Public Engagement with

    DEFF Research Database (Denmark)

    Irwin, Alan

    2015-01-01

    regarding their definition in institutional practice. Science and technology studies scholars have been especially active in challenging prevailing policy assumptions in this area and in considering how science–public relations might be reinterpreted and reconstructed. This article presents some of the key......‘Public engagement with science’ evokes a series of long-standing issues concerning the relationship between members of the public (or citizens) and matters of technical expertise. However, each of the terms ‘public,’ ‘engagement,’ and ‘science’ is open to question, and to empirical investigation...

  3. Determinants and prevalence of late HIV testing in Tijuana, Mexico.

    Science.gov (United States)

    Carrizosa, Claudia M; Blumberg, Elaine J; Hovell, Melbourne F; Martinez-Donate, Ana P; Garcia-Gonzalez, Gregorio; Lozada, Remedios; Kelley, Norma J; Hofstetter, C Richard; Sipan, Carol L

    2010-05-01

    Timely diagnosis of HIV is essential to improve survival rates and reduce transmission of the virus. Insufficient progress has been made in effecting earlier HIV diagnoses. The Mexican border city of Tijuana has one of the highest AIDS incidence and mortality rates in all of Mexico. This study examined the prevalence and potential correlates of late HIV testing in Tijuana, Mexico. Late testers were defined as participants who had at least one of: (1) an AIDS-defining illness within 1 year of first positive HIV test; (2) a date of AIDS diagnosis within 1 year of first positive HIV test; or (3) an initial CD4 cell count below 200 cells per microliter within 1 year of first positive HIV test. Medical charts of 670 HIV-positive patients from two HIV/AIDS public clinics in Tijuana were reviewed and abstracted; 362 of these patients were interviewed using a cross-sectional survey. Using multivariate logistic regression, we explored potential correlates of late HIV testing based on the Behavioral Ecological Model. From 342 participants for whom late testing could be determined, the prevalence of late testing was 43.2%. Multivariate logistic regression results (n = 275) revealed five significant correlates of late testing: "I preferred not to know I had HIV" (adjusted odds ratio [AOR] = 2.78, 1.46-5.31); clinic (AOR = 1.90, 1.06-3.41); exposure to peers engaging in high-risk sexual behavior (AOR = 1.14, 1.02-1.27); stigma regarding HIV-infected individuals (AOR = 0.65, 0.47-0.92); and stigma regarding HIV testing (AOR = 0.66, 0.45-0.97). These findings may inform the design of interventions to increase timely HIV testing and help reduce HIV transmission in the community at large.

  4. HIV transmission risk practices in rural persons living with HIV disease.

    Science.gov (United States)

    Heckman, Timothy G; Silverthorn, Monica; Waltje, Andrea; Meyers, Melissa; Yarber, William

    2003-02-01

    Little is known about continued high-risk sexual behavior of persons living with HIV disease in rural areas of the United States. However, as HIV seroprevalence rates increase in rural communities, there is an urgent need to develop interventions to assist HIV-infected rural individuals who have difficulty refraining from high-risk sex. To characterize patterns of continued high-risk sex among 216 men and women living with HIV disease in rural areas of 12 states. Cross-sectional, self-administered survey. Thirty-two percent of men and 38% of women reported that all of their sex partners in the previous 3 months were HIV-seronegative. Among the 33% of men who engaged in anal sex, 59% never or rarely used condoms. Of the 55% of women who engaged in vaginal sex in the previous 3 months, 31% never used condoms. Culturally contextualized interventions are needed to initiate and facilitate the risk-reduction efforts of HIV-infected rural persons.

  5. The prevalence and associated factors for delayed presentation for HIV care among tuberculosis/HIV co-infected patients in Southwest Ethiopia: a retrospective observational cohort.

    Science.gov (United States)

    Gesesew, Hailay; Tsehaineh, Birtukan; Massa, Desalegn; Tesfay, Amanuel; Kahsay, Hafte; Mwanri, Lillian

    2016-11-02

    A delay presentation for human immunodeficiency virus (HIV) patient's care (that is late engagement to HIV care due to delayed HIV testing or delayed linkage for HIV care after the diagnosis of HIV positive) is a critical step in the series of HIV patient care continuum. In Ethiopia, delayed presentation (DP) for HIV care among vulnerable groups such as tuberculosis (Tb) /HIV co-infected patients has not been assessed. We aimed to assess the prevalence of and factors associated with DP (CD4 prevalence of DP among Tb/HIV co-infected patients was 59.9 %. Tb/HIV co-infected patients who had a house with at least two rooms were less likely (AOR, 0.5; 95 % CI: 0.3-1.0) to present late than those having only single room. Tobacco non-users of Tb/HIV co-infected participants were also 50 % less likely (AOR, 0.5; 95 % CI: 0.3-0.8) to present late for HIV care compared to tobacco users. The relative odds of DP among Tb/HIV co-infected patients with ambulatory (AOR, 1.8; 95 % CI, 1.0-3.1) and bedridden (AOR, 8.3; 95 % CI, 2.8-25.1) functional status was higher than with working status. Three out of five Tb/HIV co-infected patients presented late for HIV care. Higher proportions of DP were observed in bedridden patients, tobacco smokers, and those who had a single room residence. These findings have intervention implications and call for effective management strategies for Tb/HIV co-infection including early HIV diagnosis and early linkage to HIV care services.

  6. 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, ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 – ... HIV and to help us Send the Message . Get the Facts What are HIV and AIDS? HIV ( ...

  8. The HIV Care Cascade Among Individuals Under Community Supervision in Baltimore, Maryland.

    Science.gov (United States)

    Zaller, Nickolas; Gordon, Michael; Bazerman, Lauri; Kuo, Irene; Beckwith, Curt

    2017-07-01

    An estimated one in seven HIV-infected individuals pass through U.S. correctional facilities each year. Transitioning from correctional to community settings may increase HIV treatment interruptions and increase the risk of continued HIV transmission in the community. This study assessed access to HIV providers in the community, antiretroviral treatment, and viral suppression to inform the development of interventions to improve HIV treatment outcomes among individuals involved in community corrections. The sample included 100 individuals under community supervision (probation or parole) in Baltimore, Maryland. While a large proportion of the study sample had undetectable HIV viral loads, 39% did not, and this represents a significant HIV transmission risk. Given the large proportion of individuals involved in the criminal justice system who are under community supervision, community corrections may be an important point of intervention to engage or reengage HIV-positive individuals who are currently out of care.

  9. Work engagement: drivers and effects

    OpenAIRE

    Bakhuys Roozeboom, M.M.C.; Schelvis, R.

    2014-01-01

    The concept of work engagement fits into the tradition of positive psychology, a recent paradigm shift in psychology which focuses on mental health rather than mental illness. This article gives an introduction to the concept of work engagement. Different definitions and viewpoints of the work engagement concept are discussed. This article will discuss the drivers of work engagement, as well as the associated effects that work engagement has on the health and wellbeing of workers and organisa...

  10. HIV prevention in care and treatment settings: baseline risk behaviors among HIV patients in Kenya, Namibia, and Tanzania.

    Directory of Open Access Journals (Sweden)

    Daniel P Kidder

    Full Text Available HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538. Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP.ClinicalTrials.gov NCT01256463.

  11. HIV Testing Among Teens Attending Therapeutic Schools: Having a Personal Source of Information About HIV/AIDS Matters!

    Science.gov (United States)

    Swenson, Rebecca R; Houck, Christopher; Sarfati, David; Emerson, Erin; Donenberg, Geri; Brown, Larry K

    2015-06-01

    Being informed and using positive coping strategies are associated with engaging in health-promoting behaviors. We assessed whether the type of information source about HIV (personal or impersonal) and coping strategies (optimism, avoidance, or emotion-focused) are associated with HIV testing among adolescents attending therapeutic schools. Participants were 417 adolescents, ages 13-19, who attended one of 20 therapeutic day schools for emotionally/behaviorally disordered youth in two US cities (Providence, RI and Chicago, IL) and completed a baseline assessment for an HIV prevention study. Among adolescents in the study, 29% reported having been tested for HIV. Adolescents were more likely to have been tested if they were older, female, Hispanic, identified as non-heterosexual, came from lower SES households, and had recently had unprotected sex. Additionally, youth who endorsed greater use of optimistic thinking and emotion-focused coping, and who reported having been informed about HIV by more personal sources, were also more likely to have been tested for HIV. In a multivariate analysis, having had recent unprotected sex and having more personal sources of information about HIV/AIDS were independently associated with HIV testing. Study findings suggest that, controlling for sociodemographic background, sexual risk behavior, and coping strategy, HIV testing among adolescents with emotional and behavioral problems may be increased when adolescents learn about HIV/AIDS from personal sources such as their healthcare providers, family, and friends.

  12. HIV-1

    African Journals Online (AJOL)

    the two major issues of stopping the AIDS epidemic and reducing poverty are addressed. Nevertheless ... affected by the same HIV epidemic as the general adult population. The resulting high absentee rates due to .... Streptococcus pneumoniae and non~typhoidal Salmonella. In the case of a Herxheimer-type reaction, ...

  13. HIV-1

    African Journals Online (AJOL)

    Leaders of the world's most powerful countries recently agreed at the G8 Summit (July 22-23, 2000) to ..... way to reduce these early deaths by reducing this toxic reaction.22 Prospective controlled trials in the .... strong leadership, they need to acknowledge the link between tuberculosis and HIV, and they need to show a ...

  14. International Engagement Strategy

    Science.gov (United States)

    2017-06-14

    throughout scientific and technical development. The International Cooperative Programs Office (ICPO) oversees S&T’s international activities, which...vulnerability assessments, RDT&E methodologies , and analyses of system interdependencies for more effective communication and collaboration between...engagement activities. OBJECTIVE 3: Monitor scientific research relevant to existing and emerging homeland security challenges. 10 OBJECTIVE 1: Identify

  15. Engage, enhance and empower

    International Development Research Centre (IDRC) Digital Library (Canada)

    Engagement. What evidence is there that different categories of women are participating in project activities and benefiting from participation? • New technologies and practices. Are women testing and adapting new and improved agricultural technologies and/or farming systems and practices that increase food production?

  16. Mars Public Engagement Overview

    Science.gov (United States)

    Johnson, Christine

    2009-01-01

    This viewgraph presentation reviews the Mars public engagement goal to understand and protect our home planet, explore the Universe and search for life, and to inspire the next generation of explorers. Teacher workshops, robotics education, Mars student imaging and analysis programs, MARS Student Imaging Project (MSIP), Russian student participation, MARS museum visualization alliance, and commercialization concepts are all addressed in this project.

  17. Unges politiske engagement

    DEFF Research Database (Denmark)

    Lieberkind, Jonas; Hansen, Niels-Henrik Møller

    2015-01-01

    I denne artikel undersøges danske unges politiske engagement. Vi vil se på, hvilke tilgange og forudsætninger danske unge har til politik, om deres politiske engagement kommer til udtryk på nye og anderledes måder, og hvorvidt deres politiske deltagelse er i konflikt med andre aktiviteter, der også...... kræver opmærksomhed og engagement. Vi vil argumentere for, at de unges syn på politik i disse år ændrer karakter, og at deres politiske deltagelse er viklet ind i og udfordret af et generelt og stigende krav fra de unge selv og omverdenen om at kunne navigere mellem stadigt flere interessesfærer: ’sig...... selv’, det sociale liv, jobs, uddannelse, karriere og fællesskabets generelle interesser (Illeris et al. 2009). Politisk deltagelse og engagement er i dette lys ikke et konkret og forudsigeligt anliggende, sådan som vi har for vane at diskutere det. For de unge fremstår det snarere som en diffus og...

  18. Mellem engagement og afmagt

    DEFF Research Database (Denmark)

    Ahrenkiel, Annegrethe; Nielsen, Birger Steen; Schmidt, Camilla

    Bogen præsenterer resultaterne fra udviklings- og forskningsprojektet "BUPL-tillidsrepræsentanten. Nye udfordringer - nye svar". Den giver et fyldigt indblik i tillidsrepræsentanternes arbejde, deres engagement, vanskeligheder og forhåbninger. På baggrund af et større værkstedsarbejde fremlægges...

  19. Music Researchers' Musical Engagement

    Science.gov (United States)

    Wollner, Clemens; Ginsborg, Jane; Williamon, Aaron

    2011-01-01

    There is an increasing awareness of the importance of reflexivity across various disciplines, which encourages researchers to scrutinize their research perspectives. In order to contextualize and reflect upon research in music, this study explores the musical background, current level of musical engagement and the listening habits of music…

  20. Analytics for Customer Engagement

    NARCIS (Netherlands)

    Bijmolt, Tammo H. A.; Leeflang, Peter S. H.; Block, Frank; Eisenbeiss, Maik; Hardie, Bruce G. S.; Lemmens, Aurelie; Saffert, Peter

    In this article, we discuss the state of the art of models for customer engagement and the problems that are inherent to calibrating and implementing these models. The authors first provide an overview of the data available for customer analytics and discuss recent developments. Next, the authors

  1. Youth, Technology, and HIV: Recent Advances and Future Directions.

    Science.gov (United States)

    Hightow-Weidman, Lisa B; Muessig, Kathryn E; Bauermeister, Jose; Zhang, Chen; LeGrand, Sara

    2015-12-01

    Technology, including mobile technologies and social media, offers powerful tools to reach, engage, and retain youth and young adults in HIV prevention and care interventions both in the USA and globally. In this report, we focus on HIV, technology, and youth, presenting a synthesis of recently published (Jan 2014-May 2015) observational and experimental studies relevant for understanding and intervening on HIV risk, prevention, and care. We present findings from a selection of the 66 relevant citations identified, highlighting studies that demonstrate a novel approach to technology interventions among youth in regard to content, delivery, target population, or public health impact. We discuss current trends globally and in the USA in how youth are using technology, as well as emergent research issues in this field-including the need for new theories for developing technology-based HIV interventions and new metrics of engagement, exposure, and evaluation.

  2. Get Tested for HIV

    Science.gov (United States)

    ... AIDS from other websites National Women and Girls HIV/AIDS Awareness Day Blog topics HIV and AIDS Breaking Down ... t Miss a Beat National Women and Girls HIV/AIDS Awareness Day National Women's Health Week Supporting Nursing Moms ...

  3. Asymptomatic HIV infection

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000682.htm Asymptomatic HIV infection To use the sharing features on this page, please enable JavaScript. Asymptomatic HIV infection is a phase of HIV/AIDS during which ...

  4. Reductions in Transmission Risk Behaviors in HIV-Positive Clients Receiving Prevention Case Management Services: Findings from a Community Demonstration Project

    Science.gov (United States)

    Gasiorowicz, Mari; Llanas, Michelle R.; DiFranceisco, Wayne; Benotsch, Eric G.; Brondino, Michael J.; Catz, Sheryl L.; Hoxie, Neil J.; Reiser, William J.; Vergeront, James M.

    2005-01-01

    Prevention case management (PCM) for HIV-infected persons is an HIV risk reduction intervention designed to assist clients who are aware of their HIV infection and who continue to engage in risk transmission behaviors. PCM combines individual risk reduction counseling with case management to address the psychosocial factors affecting HIV…

  5. HIV accomplices and adversaries in macrophage infection.

    Science.gov (United States)

    Wahl, Sharon M; Greenwell-Wild, Teresa; Vázquez, Nancy

    2006-11-01

    Cell surface and intracellular proteins in macrophages influence various steps in the life cycle of lentiviruses. Characterization of these restriction and/or cofactors is essential to understanding how macrophages become unwitting HIV hosts and in fact, can coexist with a heavy viral burden. Although many of the cellular pathways co-opted by HIV in macrophages mimic those seen in CD4+ T cells, emerging evidence reveals cellular constituents of the macrophage, which may be uniquely usurped by HIV. For example, in addition to CD4 and CCR5, membrane annexin II facilitates early steps in infection of macrophages, but not in T cells. Blockade of this pathway effectively diminishes macrophage infection. Viral binding engages a macrophage-centric signaling pathway and a transcriptional profile, including genes such as p21, which benefit the virus. Once inside the cell, multiple host cell molecules are engaged to facilitate virus replication and assembly. Although the macrophage is an enabler, it also possesses innate antiviral mechanisms, including apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3) family DNA-editing enzymes to inhibit replication of HIV. Differential expression of these enzymes, which are largely neutralized by HIV to protect its rebirth, is associated with resistance or susceptibility to the virus. Higher levels of the cytidine deaminases endow potential HIV targets with a viral shield, and IFN-alpha, a natural inducer of macrophage APOBEC expression, renders macrophages tougher combatants to HIV infection. These and other manipulatable pathways may give the macrophage a fighting chance in its battle against the virus.

  6. The Prevalence of HIV Risk Behaviors among Felony Drug Court Participants.

    Science.gov (United States)

    Festinger, David S; Dugosh, Karen L; Metzger, David S; Marlowe, Douglas B

    2012-01-01

    A small percentage of participants in a large metropolitan felony Drug Court engaged in high-risk injection drug use, but a large percentage engaged in high-risk sexual behaviors. HIV risk behaviors were associated with being male, African-American, and younger. A large proportion of Drug Court participants resided in areas of the city with a high prevalence of persons living with HIV/AIDS, thus heightening the probability of exposure to the virus.

  7. Knowledge, attitudes, and behaviors among a sample of HIV-positive and HIV-negative females visiting an urban VCT center in Haiti.

    Science.gov (United States)

    Dévieux, Jessy G; Deschamps, Marie-Marcelle; Malow, Robert M; Jean-Gilles, Michèle; Saint-Jean, Gilbert; Saint-Jean, Gilbert; Marcelin, Abdias; Pape, Jean Willam

    2009-05-01

    The knowledge, attitudes, and behaviors of over 43,000 women attending the Groupe Hatien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) Centers in Haiti between 1999-2004 were examined. Comparative analyses were conducted for several sub-samples. Analyses revealed that across the entire sample, HIV-positive women appeared to engage in more risky behaviors than HIV-negative women (p< .01); however, as a group, pregnant HIV-positive women reported safer behaviors than non-pregnant HIV-positive women (p<.01). Women from all groups were generally knowledgeable about the risk of HIV transmission through dirty needles and mother to child. However, inaccurate information about transmission through supernatural means and mosquitoes was very common. These results suggest that knowledge and education are negatively associated with HIV status in this sample. Addressing gaps in knowledge and behavior and reducing the risky behaviors of HIV-positive individuals are important directions for future programs.

  8. 77 FR 41190 - Office of Clinical and Preventive Services Funding Opportunity: National HIV Program for Enhanced...

    Science.gov (United States)

    2012-07-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Indian Health Service Office of Clinical and Preventive Services Funding Opportunity: National HIV Program for Enhanced HIV/AIDS Screening and Engagement in Care AGENCY: Indian Health Service...

  9. Mania Symptoms and HIV-Risk Behavior among Adolescents in Mental Health Treatment

    Science.gov (United States)

    Stewart, Angela J.; Theodore-Oklota, Christina; Hadley, Wendy; Brown, Larry K.; Donenberg, Geri; DiClemente, Ralph

    2012-01-01

    This study explored whether adolescents with elevated symptoms of mania (ESM+) engage in more HIV risk behaviors than those with other psychiatric disorders and examined factors associated with HIV risk behavior among ESM+ adolescents. Eight hundred forty adolescents (56% female, 58% African American, "M" age = 14.9 years) who received mental…

  10. The Synergistic Effects of Socio-Economic Factors on the Risk of HIV ...

    African Journals Online (AJOL)

    The data show social and economic factors (income, education, gender inequality and inadequate health infrastructures) are important variables influencing people's vulnerability to HIV infection; and poor women are more likely to engage in risky sexual behaviour despite awareness about the risk of HIV infection. The poor ...

  11. Age and HIV Risk and Protective Behaviors among African American Women

    Science.gov (United States)

    Corneille, Maya A.; Zyzniewski, Linda E.; Belgrave, Faye Z.

    2008-01-01

    Though HIV prevention efforts have focused on young adult women, women of all ages may engage in HIV risk behaviors and experience barriers to condom use. This article examines the effect of age on sexual risk and protective attitudes and behaviors among African American women. Unmarried heterosexual African American women between the ages of 18…

  12. Marital status and risk of HIV infection in slum settlements of Nairobi

    African Journals Online (AJOL)

    AJRH Managing Editor

    already HIV-positive or engages in risky sexual behavior, then this ... increase in HIV infection in marital partnerships. Having multiple and ... included age, ethnicity, education level, and ... study, only a total of 2,721 cases that agreed to participate in both ...... associated with increased male-perpetrated rape and sexual risks ...

  13. The church and paediatric HIV care in rural South Africa : A qualitative study

    NARCIS (Netherlands)

    W.A.J. Norder (Wilma); R.P.H. Peters (Remco); M. Kok (Maarten); S.L. van Elsland (Sabine); H.E. Struthers (Helen); M.A. Tutu (Mpho); A.M. van Furth (Marceline)

    2015-01-01

    markdownabstractReligion has substantial – positive and negative – influence on South Africa’s HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and

  14. Perceptions of HIV/AIDS leaders about faith-based organisations ...

    African Journals Online (AJOL)

    The extent of the HIV pandemic — particularly in the hardest-hit countries, including South Africa — has prompted a call for greater engagement of all groups, including faith-based organisations (FBOs). Although FBOs are known to play a substantial role in providing care and support to those affected by HIV and AIDS, ...

  15. Female Secondary School Adolescents' Sexual Behavior and School Based HIV/AIDS Education Program

    Science.gov (United States)

    Inyang, Mfrekemfon P.

    2013-01-01

    Most adolescents engage in indiscriminate sexual experimentations. This practice exposes them to the risk of contracting sexually transmitted infections including HIV/AIDS. Human immunodeficiency virus (HIV) and acquired immune deficiency syndromes (AIDS) are among the deadly diseases that exist globally. Twice as many girls, compared to boys…

  16. Measurements of Immune Responses for Establishing Correlates of Vaccine Protection Against HIV

    OpenAIRE

    Burgers, Wendy A.; Manrique, Amapola; Masopust, David; McKinnon, Lyle R.; Reynolds, Matthew R.; Rolland, Morgane; BLISH, Catherine; Chege, Gerald K.; Curran, Rhonda; Fischer, William; Herrera, Carolina; Sather, D. Noah

    2012-01-01

    Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of pro...

  17. Institutional social engagement

    Directory of Open Access Journals (Sweden)

    Prijić-Samaržija Snježana

    2016-01-01

    Full Text Available I am referring to social engagement as a value-based choice to actively intervene in social reality in order to modify existing collective identities and social practices with the goal of realizing the public good. The very term ‘engagement’, necessarily involves the starting awareness of a social deficit or flaw and presupposes a critical attitude towards social reality. In this article, I will attempt to provide arguments in favour of the thesis about the possibility (and, later, necessity of institutional engagement, critical action and even institutional protest, basing this view on the thesis that institutions are fundamentally collective or social agents whose actions must be guided by ethical and epistemic virtues.

  18. "Wan Kanyakla" (We are together): Community transformations in Kenya following a social network intervention for HIV care.

    Science.gov (United States)

    Salmen, Charles R; Hickey, Matthew D; Fiorella, Kathryn J; Omollo, Dan; Ouma, Gor; Zoughbie, Daniel; Salmen, Marcus R; Magerenge, Richard; Tessler, Robert; Campbell, Harold; Geng, Elvin; Gandhi, Monica; Bukusi, Elizabeth A; Cohen, Craig R

    2015-12-01

    In sub-Saharan Africa, failure to initiate and sustain HIV treatment contributes to significant health, psychosocial, and economic impacts that burden not only infected individuals but diverse members of their social networks. Yet, due to intense stigma, the responsibility for managing lifelong HIV treatment rests solely, and often secretly, with infected individuals. We introduce the concept of "HIV risk induction" to suggest that social networks of infected individuals share a vested interest in improving long-term engagement with HIV care, and may represent an underutilized resource for improving HIV/AIDS outcomes within high prevalence populations. In 2012, we implemented a 'microclinic' intervention to promote social network engagement in HIV/AIDS care and treatment. A microclinic is a therapy management collective comprised of a small group of neighbors, relatives, and friends who are trained as a team to provide psychosocial and adherence support for HIV-infected members. Our study population included 369 patients on ART and members of their social networks on Mfangano Island, Kenya, where HIV prevalence approaches 30%. Here we report qualitative data from 18 focus group discussions conducted with microclinic participants (n = 82), community health workers (n = 40), and local program staff (n = 39). Participants reported widespread acceptability and enthusiasm for the microclinic intervention. Responses highlight four overlapping community transformations regarding HIV care and treatment, namely (1) enhanced HIV treatment literacy (2) reduction in HIV stigma, (3) improved atmosphere for HIV status disclosure and (4) improved material and psychosocial support for HIV-infected patients. Despite challenges, participants describe an emerging sense of "collective responsibility" for treatment among HIV-infected and HIV-uninfected members of social networks. The lived experiences and community transformations highlighted by participants enrolled in this social

  19. Academic Engagement and Commercialisation

    DEFF Research Database (Denmark)

    Perkmann, Markus; Tartari, Valentina; McKelvey, Maureen

    2013-01-01

    A considerable body of work highlights the relevance of collaborative research, contract research, consulting and informal relationships for university–industry knowledge transfer. We present a systematic review of research on academic scientists’ involvement in these activities to which we refer...... as ‘academic engagement’. Apart from extracting findings that are generalisable across studies, we ask how academic engagement differs from commercialisation, defined as intellectual property creation and academic entrepreneurship. We identify the individual, organisational and institutional antecedents...

  20. Frafald og engagement

    DEFF Research Database (Denmark)

    Jørgensen, Christian Helms; Pedersen, Lene Tanggaard; Nielsen, Klaus

    Denne rapport beskriver de første resultater fra den kvalitative del af et forskningsprojekt om frafald og fastholdelse i dansk erhvervsuddannelse finansieret af Det Strategiske Forskningsråd i perioden 2009-2012. Resultaterne bygger på de første elevinterview gennemført i efteråret 2009 og fokus...... fokuserer eksplicit på elevernes oplevelse af eget engagement eller mangel på samme på erhvervsskolernes grundforløb....