WorldWideScience

Sample records for therapy-induced hiv type

  1. Full-length characterization of A1/D intersubtype recombinant genomes from a therapy-induced HIV type 1 controller during acute infection and his noncontrolling partner

    DEFF Research Database (Denmark)

    Fomsgaard, Anders; Vinner, Lasse; Therrien, Dominic

    2008-01-01

    To increase the understanding of mechanisms of HIV control we have genetically and immunologically characterized a full-length HIV-1 isolated from an acute infection in a rare case of undetectable viremia. The subject, a 43-year-old Danish white male (DK1), was diagnosed with acute HIV-1 infection...... after 1 year in Uganda. Following transient antiretroviral therapy DK1 maintained undetectable viral load for more than 10 years. His Ugandan wife (UG1) developed high viral load. HIV-1 sequences from both individuals were compared by bootscanning for recombination break points. Diversity plots...... homology in shared regions. Four of seven crossover points were identical; however, the env gene from UG1 was subtype D, but A1 in DK1. Both viruses encoded proteins of the expected length and replicated equally well in vitro. DK1 and UG1 shared the HLA-A02 tissue type. HLA-A02-restricted CD8(+) T cell IFN...

  2. Full-length characterization of A1/D intersubtype recombinant genomes from a therapy-induced HIV type 1 controller during acute infection and his noncontrolling partner

    DEFF Research Database (Denmark)

    Fomsgaard, A.; Vinner, L.; Therrien, D.

    2008-01-01

    To increase the understanding of mechanisms of HIV control we have genetically and immunologically characterized a full-length HIV-1 isolated from an acute infection in a rare case of undetectable viremia. The subject, a 43-year-old Danish white male (DK1), was diagnosed with acute HIV-1 infection...... after 1 year in Uganda. Following transient antiretroviral therapy DK1 maintained undetectable viral load for more than 10 years. His Ugandan wife (UG1) developed high viral load. HIV-1 sequences from both individuals were compared by bootscanning for recombination break points. Diversity plots......-gamma IC-FACS response in DK1 was detected against only one (Pol(476)) of 23 conserved epitopes. Neutralizing antibodies were induced only to the homologous isolate. These results indicate an A1D intersubtype recombination or transmission of a minor variant. Transient early antiretroviral therapy may have...

  3. HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury

    Directory of Open Access Journals (Sweden)

    Manuela G. Neuman

    2012-01-01

    Full Text Available The present paper describes possible connections between antiretroviral therapies (ARTs used to treat human immunodeficiency virus (HIV infection and adverse drug reactions (ADRs encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication.

  4. Polyacrylamide Gel Treatment of Antiretroviral Therapy-induced Facial Lipoatrophy in HIV Patients

    DEFF Research Database (Denmark)

    Mansor, Samreen; Breiting, Vibeke Bro; Dahlstrøm, Karin

    2011-01-01

    BACKGROUND: Today, highly active antiretroviral therapy is lifesaving for most HIV-infected patients, but the treatment can result in facial lipoatrophy, which changes the face so radically that patients may develop severe psychological and social problems. Since 2001 polyacrylamide gel (PAAG) has...... been used successfully in HIV patients abroad. This article describes the results of a Danish study. METHODS: Forty HIV patients recruited from two major referral hospitals in the capitol area of Copenhagen, Denmark, each received a series of PAAG gel injections (small deposits in several sessions...

  5. Prognosis of type 1 autoimmune pancreatitis after corticosteroid therapy-induced remission in terms of relapse and diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Masaki Miyazawa

    Full Text Available Relapse and diabetes mellitus (DM are major problems for the prognosis of autoimmune pancreatitis (AIP. We examined the prognosis of type 1 AIP after corticosteroid therapy (CST-induced remission in terms of relapse and DM.The study enrolled 82 patients diagnosed with type 1 AIP who achieved remission with CST. We retrospectively evaluated the relapse rate in terms of the administration period of CST, clinical factors associated with relapse, and the temporal change in glucose tolerance.During follow-up, 32 patients (39.0% experienced relapse. There was no significant clinical factor that could predict relapse before beginning CST. AIP patients who ceased CST within 2 or 3 years experienced significantly earlier relapse than those who had the continuance of CST (p = 0.050 or p = 0.020. Of the 37 DM patients, 15 patients (40.5% had pre-existing DM, 17 (45.9% showed new-onset DM, and 5 (13.5% developed CST-induced DM. Patients with new-onset DM were significantly more likely to show improvement (p = 0.008 than those with pre-existing DM.It was difficult to predict relapse of AIP based on clinical parameters before beginning CST. Relapse was likely to occur within 3 years after the beginning of CST and maintenance of CST for at least 3 years reduced the risk of relapse. The early initiation of CST for AIP with impaired glucose tolerance is desirable because pre-existing DM is refractory to CST.

  6. Knowledge and Preference of HIV Testing Types Among Antenatal ...

    African Journals Online (AJOL)

    Context Knowledge of different HIV testing modules is necessary to make an informed consent. The basic conditions of confidentiality, voluntary and counseling (pre-and-post) should apply in all HIV testing. Objective To assess the knowledge and preference of HIV counseling and testing types among antenatal women at ...

  7. Rapid Assay for Simultaneous Detection and Differentiation of Immunoglobulin G Antibodies to Human Immunodeficiency Virus Type 1 (HIV-1) Group M, HIV-1 Group O, and HIV-2

    OpenAIRE

    Vallari, Ana S.; Hickman, Robert K.; Hackett, John R.; Brennan, Catherine A.; Varitek, Vincent A.; Devare, Sushil G.

    1998-01-01

    A rapid immunodiagnostic test that detects and discriminates human immunodeficiency virus (HIV) infections on the basis of viral type, HIV type 1 (HIV-1) group M, HIV-1 group O, or HIV-2, was developed. The rapid assay for the detection of HIV (HIV rapid assay) was designed as an instrument-free chromatographic immunoassay that detects immunoglobulin G (IgG) antibodies to HIV. To assess the performance of the HIV rapid assay, 470 HIV-positive plasma samples were tested by PCR and/or Western b...

  8. Serological profiles of Herpes simplex virus type 2 among HIV ...

    African Journals Online (AJOL)

    Herpes simplex virus type-2 (HSV-2) is the major cause of genital ulcer diseases (GUD) consequently a significant factor for the acquisition and transmission of human immunodeficiency virus (HIV). Despite its importance there is paucity of data regarding the magnitude of HSV-2 in non-HIV infected population in ...

  9. Anti-CD3/Anti-CXCL10 Antibody Combination Therapy Induces a Persistent Remission of Type 1 Diabetes in Two Mouse Models.

    Science.gov (United States)

    Lasch, Stanley; Müller, Peter; Bayer, Monika; Pfeilschifter, Josef M; Luster, Andrew D; Hintermann, Edith; Christen, Urs

    2015-12-01

    Anti-CD3 therapy of type 1 diabetes results in a temporary halt of its pathogenesis but does not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was superior to monotherapy with anti-CD3 or anti-CXCL10 alone. The combination therapy prevented islet-specific T cells from reentering the islets of Langerhans and thereby blocked the autodestructive process. In addition, the local immune balance in the pancreas was shifted toward a regulatory phenotype. A sequential temporal inactivation of T cells and blockade of T-cell migration might constitute a novel therapy for patients with type 1 diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Types and predictors of partner reactions to HIV status disclosure ...

    African Journals Online (AJOL)

    Abstract. Background and objective: Our aim was to describe the types and determinants of partner reactions to HIV-status dis- closure among adults attending an antiretroviral therapy-(ART) clinic in the Bayelsa State, Nigeria. Methods: A cross-sectional study was undertaken between January and March 2013 among ...

  11. The burden and morhological types of anaemia among HIV infected ...

    African Journals Online (AJOL)

    Conclusions and recommendations: The finding suggests that anaemia is common among HIV children even in the era of HAART. Microcytic hypochromic anaemia was the commonest type of anaemia suggesting the role of iron deficiency or anaemia of chronic infection. Further studies on the aetiology of anaemia in HIV ...

  12. Rapid assay for simultaneous detection and differentiation of immunoglobulin G antibodies to human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2.

    Science.gov (United States)

    Vallari, A S; Hickman, R K; Hackett, J R; Brennan, C A; Varitek, V A; Devare, S G

    1998-12-01

    A rapid immunodiagnostic test that detects and discriminates human immunodeficiency virus (HIV) infections on the basis of viral type, HIV type 1 (HIV-1) group M, HIV-1 group O, or HIV-2, was developed. The rapid assay for the detection of HIV (HIV rapid assay) was designed as an instrument-free chromatographic immunoassay that detects immunoglobulin G (IgG) antibodies to HIV. To assess the performance of the HIV rapid assay, 470 HIV-positive plasma samples were tested by PCR and/or Western blotting to confirm the genotype of the infecting virus. These samples were infected with strains that represented a wide variety of HIV strains including HIV-1 group M (subtypes A through G), HIV-1 group O, and HIV-2 (subtypes A and B). The results showed that the HIV genotype identity established by the rapid assay reliably (469 of 470 samples) correlates with the HIV genotype identity established by PCR or Western blotting. A total of 879 plasma samples were tested for IgG to HIV by a licensed enzyme immunoassay (EIA) (470 HIV-positive samples and 409 HIV-negative samples). When they were tested by the rapid assay, 469 samples were positive and 410 were negative (99.88% agreement). Twelve seroconversion panels were tested by both the rapid assay and a licensed EIA. For nine panels identical results were obtained by the two assays. For the remaining three panels, the rapid assay was positive one bleed later in comparison to the bleed at which the EIA was positive. One hundred three urine samples, including 93 urine samples from HIV-seropositive individuals and 10 urine samples from seronegative individuals, were tested by the rapid assay. Ninety-one of the ninety-three urine samples from HIV-seropositive individuals were found to be positive by the rapid assay. There were no false-positive results (98.05% agreement). Virus in all urine samples tested were typed as HIV-1 group M. These results suggest that a rapid assay based on the detection of IgG specific for selected

  13. HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 INFECTION STATUS AND IN-VITRO SUSCEPTIBILITY TO HIV-INFECTION AMONG HIGH-RISK HIV-1 SERONEGATIVE HEMOPHILIACS

    NARCIS (Netherlands)

    LEDERMAN, MM; JACKSON, JB; KRONER, BL; WHITE, GC; EYSTER, ME; ALEDORT, LM; HILGARTNER, MW; KESSLER, CM; COHEN, AR; KIGER, KP; GOEDERT, JJ

    Blood samples were obtained from 16 hemophiliacs who had a 50%-94% defined risk of human immunodeficiency virus (HIV type 1 infection on the basis of treatment history and from 14 controls not at risk for HIV infection. HIV-1 was not detected in any of 12 patient samples by cocultivation nor in 14

  14. Autophagy induction by histone deacetylase inhibitors inhibits HIV type 1.

    Science.gov (United States)

    Campbell, Grant R; Bruckman, Rachel S; Chu, Yen-Lin; Spector, Stephen A

    2015-02-20

    Histone deacetylase inhibitors (HDACi) are being evaluated in a "shock-and-kill" therapeutic approach to reverse human immunodeficiency virus type-1 (HIV) latency from CD4(+) T cells. Using this approach, HDACi have induced HIV RNA synthesis in latently infected cells from some patients. The hope is that the increase in viral production will lead to killing of the infected cell either by the virus itself or by the patient's immune system, a "sterilizing cure." Although administered within the context of combination antiretroviral therapy, the infection of bystander cells remains a concern. In this study, we investigated the effect of HDACi (belinostat, givinostat, panobinostat, romidepsin, and vorinostat) on the productive infection of macrophages. We demonstrate that the HDACi tested do not alter the initial susceptibility of macrophages to HIV infection. However, we demonstrate that HDACi decrease HIV release from macrophages in a dose-dependent manner (belinostat the canonical autophagy pathway. This mechanism involves unc-51-like autophagy-activating kinase 1 (ULK1) and the inhibition of the mammalian target of rapamycin and requires the formation of autophagosomes and their maturation into autolysosomes in the absence of increased cell death. These data provide further evidence in support of a role for autophagy in the control of HIV infection and suggest that careful consideration of off-target effects will be essential if HDACi are to be a component of a multipronged approach to eliminate latently infected cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Human immunodeficiency virus type-1 (HIV-1) genetic diversity and ...

    African Journals Online (AJOL)

    PROGMANAGER

    2013-04-24

    Apr 24, 2013 ... Human immunodeficiency virus type-1 (HIV-1) genetic diversity and prevalence of antiretroviral drug resistance mutations in treatment-naïve adults in Jos,. North Central Nigeria. Anejo-Okopi J. A.1*, Agbaji O. O.1,2, Agaba P. A.1,3, Ugoagwu P. O.1, Were K.4, Onywera H.4,. Owiti P.4, Isa S. E1,2, Otecko N.4 ...

  16. 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.

  17. Detection of human immunodeficiency virus type 1 and type 2 antibodies by a new automated microparticle immunoassay AxSYM HIV-1/HIV-2.

    Science.gov (United States)

    Weber, B; Behrens, N; Doerr, H W

    1997-01-01

    A new automated microparticle enzyme immunoassay (MEIA) for the AxSYM instrument developed recently by Abbott Laboratories was compared with two established assays, i.e. HIV-1/HIV-2 3rd Gen. Plus EIA (Abbott, Delkenheim, FRG) and Wellcozyme HIV 1 + 2 (Murex Diagnostics, Dartford, England) devised for the detection of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies. A total of 7293 serum samples were tested by the AxSYM HIV-1/HIV-2. The test panel included seroconversions (n = 22), samples from HIV-1 and HIV-2 positive individuals, hospitalized patients, blood donors, high risk individuals. To challenge further the specificity of the assays, large numbers of EIA repeatedly reactive but Western blot negative samples, potentially cross-reactive sera, Western blot indeterminate specimens and samples from pregnant women were tested. In four seroconversion panels, HIV-1 infection was detected one bleed earlier with the AxSYM HIV-1/HIV-2 than with the Abbott HIV-1/HIV-2 3rd Gen. Plus EIA. Although the AxSYM HIV-1/HIV-2 was tested with a higher number of challenging sera than the alternative assays, the specificity was very high (99.4%). The highest number of false positive results was obtained with serum samples that were repeatedly reactive in EIAs different from those compared in the present study. The automated AxSYM system permits the testing of a large sample number in a rapid turn-around time and by random access urgent tests can be carried out even when an assay is in progress.

  18. An HIV-1 Infected Patient with Neurofibromatosis Type 1: A Case ...

    African Journals Online (AJOL)

    Alasia Datonye

    Background: Although HIV-1 infection predisposes an individual to well defined neoplasia, neurofibromas have not been reported as some of the typical ones. The association between HIV-1 infection and neurofibromatosis type 1, a genetic disorder, should be of interest because HIV infection could alter the natural.

  19. An HIV-1 infected patient with Neurofibromatosis type 1: A case report

    African Journals Online (AJOL)

    Background: Although HIV-1 infection predisposes an individual to well defined neoplasia, neurofibromas have not been reported as some of the typical ones. The association between HIV-1 infection and neurofibromatosis type 1, a genetic disorder, should be of interest because HIV infection could alter the natural biology ...

  20. HIV-antibody complexes enhance production of type I interferon by plasmacytoid dendritic cells.

    Science.gov (United States)

    Veenhuis, Rebecca T; Freeman, Zachary T; Korleski, Jack; Cohen, Laura K; Massaccesi, Guido; Tomasi, Alessandra; Boesch, Austin W; Ackerman, Margaret E; Margolick, Joseph B; Blankson, Joel N; Chattergoon, Michael A; Cox, Andrea L

    2017-10-30

    Type I IFN production is essential for innate control of acute viral infection; however, prolonged high-level IFN production is associated with chronic immune activation in HIV-infected individuals. Although plasmacytoid DCs (pDCs) are a primary source of IFN, the mechanisms that regulate IFN levels following the acute phase are unknown. We hypothesized that HIV-specific Ab responses regulate late IFN production. We evaluated the mechanism through which HIV-activated pDCs produce IFN as well as how both monoclonal HIV-specific Abs and Abs produced in natural HIV infection modulated normal pDC sensing of HIV. We found that HIV-induced IFN production required TLR7 signaling, receptor-mediated entry, fusion, and viral uncoating, but not endocytosis or HIV life cycle stages after uncoating. Abs directed against the HIV envelope that do not interfere with CD4 binding markedly enhanced the IFN response, irrespective of their ability to neutralize CD4+ T cell infection. Ab-mediated enhancement of IFN production required Fc γ receptor engagement, bypassed fusion, and initiated signaling through both TLR7 and TLR9, which was not utilized in the absence of Ab. Polyclonal Abs isolated from HIV-infected subjects also enhanced pDC production of IFN in response to HIV. Our data provide an explanation for high levels of IFN production and immune activation in chronic HIV infection.

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

    Science.gov (United States)

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

    2016-01-01

    Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-α/β receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1–infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1–induced immune hyperactivation and rescued anti–HIV-1 immune responses in T cells from HIV-1–infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1–infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1–associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART. PMID:27941247

  2. C-type lectin Mermaid inhibits dendritic cell mediated HIV-1 transmission to CD4+ T cells

    NARCIS (Netherlands)

    Nabatov, Alexey A.; de Jong, Marein A. W. P.; de Witte, Lot; Bulgheresi, Silvia; Geijtenbeek, Teunis B. H.

    2008-01-01

    Dendritic cells (DCs) are important in HIV-1 transmission; DCs capture invading HIV-1 through the interaction of the gp120 oligosaccharides with the C-type lectin DC-SIGN and migrate to the lymphoid tissues where HIV-1 is transmitted to T cells. Thus, the HIV-1 envelope glycoprotein gp120 is an

  3. Origin of HIV type 1 in colonial French Equatorial Africa?

    Science.gov (United States)

    Chitnis, A; Rawls, D; Moore, J

    2000-01-01

    Sociocultural factors during the postcolonial period have been implicated as paramount in generating conditions that promoted both the origin and subsequent epidemic spread of HIV-1 in Africa. We suggest, however, that the origin of the disease may lie in the interaction between colonial practices (e.g., labor camps, nonsterile vaccination campaigns) and traditional bushmeat hunting in French Equatorial Africa. Both the epidemiology of HIV-2 and the colonial history of West Africa appear more complex, but similar conditions existed there and may have contributed to the origin of HIV-2. Focusing the search for the origins of HIV-1 and HIV-2 on this earlier time period may contribute to understanding the evolution of the HIV viruses and the dynamics of emerging diseases.

  4. Herpes simplex virus type 2 enhances HIV-1 susceptibility by affecting langerhans cell function

    NARCIS (Netherlands)

    M.A.W.P. de Jong (Marein); L. de Witte (Lot); M.E. Taylor (Maureen); T.B.H. Geijtenbeek (Teunis)

    2010-01-01

    textabstractGenital herpes is the most prevalent viral sexually transmitted infection worldwide and is mainly caused by HSV type 2 (HSV-2). HSV-2 infection enhances HIV-1 susceptibility, even in the absence of clinical symptoms. In this study, we investigated the effect of HSV-2 on HIV-1

  5. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.

    Science.gov (United States)

    Zhen, Anjie; Rezek, Valerie; Youn, Cindy; Lam, Brianna; Chang, Nelson; Rick, Jonathan; Carrillo, Mayra; Martin, Heather; Kasparian, Saro; Syed, Philip; Rice, Nicholas; Brooks, David G; Kitchen, Scott G

    2017-01-03

    Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection.

  6. Mortality and morbidity among HIV type-1-infected patients during the first 5 years of a multicountry HIV workplace programme in Africa.

    Science.gov (United States)

    Van der Borght, Stefaan F; Clevenbergh, Philippe; Rijckborst, Henk; Nsalou, Paul; Onyia, Ngozi; Lange, Joep M; de Wit, Tobias F Rinke; Van der Loeff, Maarten F Schim

    2009-01-01

    This study aimed to evaluate the effectiveness of an HIV workplace programme in sub-Saharan Africa. The international brewing company, Heineken, introduced an HIV workplace programme in its African subsidiaries in 2001. Beneficiaries from 16 sites in 5 countries were eligible. HIV type-1 (HIV-1)-infected individuals were assessed clinically and immunologically, and started highly active antiretroviral therapy (HAART) if they had AIDS or had a CD4+ T-cell count long-term high survival was achieved.

  7. Synthetic peptides define the fine specificity of the human immunodeficiency virus (HIV) gp160 humoral immune response in HIV type 1-infected chimpanzees.

    OpenAIRE

    Warren, R Q; Wolf, H; Shuler, K R; Eichberg, J W; Zajac, R A; Boswell, R N; Kanda, P; Kennedy, R C

    1990-01-01

    The fine specificities of antibodies produced against human immunodeficiency virus type 1 (HIV-1) gp160 were examined in sera from 23 HIV-1-infected chimpanzees. These animals had been infected with one of six isolates of HIV-1. Sera were screened by enzyme-linked immunosorbent assay for reactivity against seven synthetic peptides corresponding to regions of gp160. Chimpanzees appear to remain healthy after infection with HIV-1, suggesting that these animals may prevent extensive spread of th...

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

    Directory of Open Access Journals (Sweden)

    Ting Pan

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

  9. The pharmacokinetics, safety and efficacy of boosted saquinavir tablets in HIV type-1-infected pregnant women.

    NARCIS (Netherlands)

    Lugt, J. van der; Colbers, A.; Molto, J.; Hawkins, D.; Ende, M. van der; Vogel, M.; Wyen, C.; Schutz, M.; Koopmans, P.; Ruxrungtham, K.; Richter, C.; Burger, D.M.

    2009-01-01

    BACKGROUND: Pregnancy affects the pharmacokinetics of most protease inhibitors. Saquinavir, when administered in a tablet formulation, has not been studied extensively in this setting. METHODS: A pharmacokinetic, prospective, multicentre trial of HIV type-1-infected pregnant women treated with

  10. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Science.gov (United States)

    Behbahani, Mandana

    2014-01-01

    Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs) used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR) assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50) values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies.

  11. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Directory of Open Access Journals (Sweden)

    Mandana Behbahani

    Full Text Available Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50 values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies.

  12. Molecular typing of the local HIV-1 epidemic in Serbia.

    Science.gov (United States)

    Siljic, Marina; Salemovic, Dubravka; Jevtovic, Djordje; Pesic-Pavlovic, Ivana; Zerjav, Sonja; Nikolic, Valentina; Ranin, Jovan; Stanojevic, Maja

    2013-10-01

    Worldwide HIV-1 pandemic is becoming increasingly complex, with growing heterogeneity of subtypes and recombinant viruses. Previous studies have documented HIV-1 subtype B as the predominant one in Serbia, with limited presence and genetic diversity of non B subtypes. In recent years, MSM transmission has become the most frequently reported risk for HIV infection among newly diagnosed patients in Serbia, but very little is known of the network structure and dynamics of viral transmission in this and other risk groups. To gain insight about the HIV-1 subtypes distribution pattern as well as characteristics of HIV-1 transmission clusters in Serbia, we analyzed the genetic diversity of the pol gene segment in 221 HIV-1-infected patients sampled during 2002-2011. Subtype B was found to still be the most prevalent one in Serbia, accounting for over 90% of samples, while greater diversity of other subtypes was found than previously reported, including subtypes G, C, A, F, CRF01 and CRF02. In total, 41.3% of analyzed subtype B sequences were found associated in transmission clusters/network, that are highly related with MSM transmission route. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. 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

  14. Type I Interferon Contributes to CD4+ T Cell Depletion Induced by Infection with HIV-1 in the Human Thymus▿

    OpenAIRE

    Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

    2011-01-01

    Persistent induction of type 1 interferon (IFN) is associated with human immunodeficiency virus type 1 (HIV-1) infection. We report here that the pathogenic HIV strain R3A (HIV-R3A) induced high levels of type 1 IFN, while the nonpathogenic HIV-R3B showed no significant induction in human fetal thymus organ culture (HFTOC). We found that IFN contributed to the depletion of human T cells by HIV-R3A in a fusion-independent fashion. The R3B recombinant with the R3A Env V1V2 domain (R3B/A-V1V2) w...

  15. Evidence for Innate Immune System Activation in HIV Type 1–Infected Elite Controllers

    Science.gov (United States)

    Krishnan, Sonya; Wilson, Eleanor M. P.; Sheikh, Virginia; Rupert, Adam; Mendoza, Daniel; Yang, Jun; Lempicki, Richard; Migueles, Stephen A.; Sereti, Irini

    2014-01-01

    Background. Elite controllers maintain high CD4+ T-cell counts and suppress plasma human immunodeficiency virus (HIV) viremia in the absence of antiretroviral therapy (ART). It is unclear whether levels of biomarkers associated with coagulation, monocyte activation, and inflammation, which are linked to HIV-associated mortality, differ among elite controllers, ART recipients with suppressed viremia (plasma HIV type 1 RNA load, elite controllers, 68 ART recipients with suppressed viremia, and 35 HIV-negative participants were evaluated. Levels of biomarkers in cryopreserved plasma were measured by enzyme-linked immunosorbent assay and electrochemiluminescence-based assay. Cryopreserved peripheral blood mononuclear cells were used to assess monocyte phenotype and function and interferon-inducible gene expression (IFIG). Nonparametric testing was used to compare median values among groups. Results. CD4+ T-cell counts were similar between elite controllers and HIV-negative controls but significantly lower in ART recipients with suppressed viremia. Levels of C-reactive protein and interleukin 6 were higher and IFIG upregulated in both HIV-positive groups, compared with HIV-negative controls. D-dimer and soluble tissue factor levels were significantly elevated in elite controllers, compared with those in ART recipients with suppressed viremia and HIV-negative controls (P elite controllers (and ART recipients with suppressed viremia) expressed lower CCR2 and higher CX3CR1 levels than monocytes from HIV-negative controls. In addition, elite controllers had a significantly higher proportion of CD14++CD16+ monocytes, compared with HIV-negative controls. Conclusion. Elite controllers maintain control of plasma HIV viremia and have evidence of an activated innate immune response. PMID:24185941

  16. Evidence for innate immune system activation in HIV type 1-infected elite controllers.

    Science.gov (United States)

    Krishnan, Sonya; Wilson, Eleanor M P; Sheikh, Virginia; Rupert, Adam; Mendoza, Daniel; Yang, Jun; Lempicki, Richard; Migueles, Stephen A; Sereti, Irini

    2014-03-01

    Elite controllers maintain high CD4(+) T-cell counts and suppress plasma human immunodeficiency virus (HIV) viremia in the absence of antiretroviral therapy (ART). It is unclear whether levels of biomarkers associated with coagulation, monocyte activation, and inflammation, which are linked to HIV-associated mortality, differ among elite controllers, ART recipients with suppressed viremia (plasma HIV type 1 RNA load, elite controllers, 68 ART recipients with suppressed viremia, and 35 HIV-negative participants were evaluated. Levels of biomarkers in cryopreserved plasma were measured by enzyme-linked immunosorbent assay and electrochemiluminescence-based assay. Cryopreserved peripheral blood mononuclear cells were used to assess monocyte phenotype and function and interferon-inducible gene expression (IFIG). Nonparametric testing was used to compare median values among groups. CD4(+) T-cell counts were similar between elite controllers and HIV-negative controls but significantly lower in ART recipients with suppressed viremia. Levels of C-reactive protein and interleukin 6 were higher and IFIG upregulated in both HIV-positive groups, compared with HIV-negative controls. D-dimer and soluble tissue factor levels were significantly elevated in elite controllers, compared with those in ART recipients with suppressed viremia and HIV-negative controls (P elite controllers (and ART recipients with suppressed viremia) expressed lower CCR2 and higher CX3CR1 levels than monocytes from HIV-negative controls. In addition, elite controllers had a significantly higher proportion of CD14(++)CD16(+) monocytes, compared with HIV-negative controls. Elite controllers maintain control of plasma HIV viremia and have evidence of an activated innate immune response.

  17. Type I interferon responses are impaired in latently HIV infected cells.

    Science.gov (United States)

    Ranganath, Nischal; Sandstrom, Teslin S; Fadel, Saleh; Côté, Sandra C; Angel, Jonathan B

    2016-09-09

    The latent HIV-1 reservoir represents the primary barrier to the eradication of HIV-1 infection. The design of novel reservoir-clearance strategies, however, is impeded in part by the inability to distinguish latently HIV-infected cells from uninfected cells. Significant impairment of the type I interferon (IFN-I) response is observed during productive HIV-1 infection. Although this remains poorly described in the context of latent HIV-1 infection, presence of potential defects may serve as a novel therapeutic target. Therefore, IFN-I pathways were characterized using two latently HIV-1-infected cell lines, U1 and OM10.1, in comparison to their respective uninfected parental U937 and HL60 cell lines. Constitutive expression and induction of important mediators of IFN-I signaling including IFNα/β cytokines, IFNAR1, MHC-I, ISG15, and PKR were evaluated following exogenous IFNα or poly(I:C) treatment. Differences in basal expression of IFNAR1, MHC-I, and PKR were observed between the latently HIV-1 infected and uninfected cell lines. In parallel, significant impairments in the induction of MHC-I, ISG15 and PKR, as well as secretion of IFNα/β cytokines were observed in response to appropriate exogenous stimulation within the two latently HIV-infected U1 and OM10.1 cells, relative to their HIV-uninfected parental cells. In comparison to the HIV-uninfected U937 and HL60 cell lines, widespread defects in IFN-I responsiveness were observed within the latently HIV-infected U1 and OM10.1 cells. These impairments represent novel therapeutic targets, which may be amenable to strategies currently employed in cancer therapy.

  18. 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

  19. Genital herpes simplex virus type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease.

    Science.gov (United States)

    Nixon, Briana; Fakioglu, Esra; Stefanidou, Martha; Wang, Yanhua; Dutta, Monica; Goldstein, Harris; Herold, Betsy C

    2014-02-15

    Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

  20. Syphilis and HIV co-infection. Epidemiology, treatment and molecular typing of Treponema pallidum.

    Science.gov (United States)

    Salado-Rasmussen, Kirsten

    2015-12-01

    The studies included in this PhD thesis examined the interactions of syphilis, which is caused by Treponema pallidum, and HIV. Syphilis reemerged worldwide in the late 1990s and hereafter increasing rates of early syphilis were also reported in Denmark. The proportion of patients with concurrent HIV has been substantial, ranging from one third to almost two thirds of patients diagnosed with syphilis some years. Given that syphilis facilitates transmission and acquisition of HIV the two sexually transmitted diseases are of major public health concern. Further, syphilis has a negative impact on HIV infection, resulting in increasing viral loads and decreasing CD4 cell counts during syphilis infection. Likewise, HIV has an impact on the clinical course of syphilis; patients with concurrent HIV are thought to be at increased risk of neurological complications and treatment failure. Almost ten per cent of Danish men with syphilis acquired HIV infection within five years after they were diagnosed with syphilis during an 11-year study period. Interestingly, the risk of HIV declined during the later part of the period. Moreover, HIV-infected men had a substantial increased risk of re-infection with syphilis compared to HIV-uninfected men. As one third of the HIV-infected patients had viral loads >1,000 copies/ml, our conclusion supported the initiation of cART in more HIV-infected MSM to reduce HIV transmission. During a five-year study period, including the majority of HIV-infected patients from the Copenhagen area, we observed that syphilis was diagnosed in the primary, secondary, early and late latent stage. These patients were treated with either doxycycline or penicillin and the rate of treatment failure was similar in the two groups, indicating that doxycycline can be used as a treatment alternative - at least in an HIV-infected population. During a four-year study period, the T. pallidum strain type distribution was investigated among patients diagnosed by PCR

  1. 75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

    Science.gov (United States)

    2010-04-30

    ... Immunodeficiency Virus Type 1 (HIV-1) Nucleic Acid Test (NAT) and Hepatitis C Virus (HCV) NAT, on testing... test results, HIV-1 p24 antigen test results, and anti-HCV test results that were provided in the FDA... (Anti-HCV),'' August 5, 1993; ``Recommendations for Donor Screening with a Licensed Test for HIV-1...

  2. Adolescent Use of Two Types of HIV Prevention Agencies

    Science.gov (United States)

    Hohman, Melinda; Shillington, Audrey M.; Min, Jong Won; Clapp, John D.; Mueller, Kristin; Hovell, Melbourne

    2008-01-01

    This study compared two groups of adolescents seeking help at HIV prevention drop-in agencies. The first group attended agencies in low-income Hispanic neighborhoods which recruited within the locale. The second group of youth attended agencies that recruited based upon a specific population--they targeted homeless and LGBQ youth. We explored the…

  3. Molecular epidemiology of HIV type 1 subtypes in Rwanda.

    Science.gov (United States)

    Kemal, Kimdar S; Anastos, Kathryn; Weiser, Barbara; Ramirez, Christina M; Shi, Qiuhu; Burger, Harold

    2013-06-01

    HIV-1 infection is characterized by genetic diversity, with multiple subtypes and recombinant variants circulating, particularly in sub-Saharan Africa. During the Rwandan genocide, many women experienced multiple rapes and some became HIV-1 infected. We studied plasma and peripheral blood mononuclear cells (PBMCs) from 30 infected women comprising two exposure groups: those with numerous contacts, raped multiple times, and women with one lifetime sexual partner and no history of rape. Population-based sequences from gag, pol, and env genes were analyzed to determine HIV-1 subtypes and intersubtype recombination. Individual plasma-derived variants from 12 women were also analyzed. Subtype A was found in 24/30 (80%), intersubtype recombination (AC and AD) in 4/30 (13%), and subtypes C and D in 1/30 each. In two subjects, the pattern of HIV-1 recombination differed between plasma and PBMC-derived sequences. Intersubtype recombination was common, although there were no significant differences in subtype or recombination rates between exposure groups.

  4. HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation.

    Science.gov (United States)

    Hove-Skovsgaard, Malene; Gaardbo, Julie Christine; Kolte, Lilian; Winding, Kamilla; Seljeflot, Ingebjørg; Svardal, Asbjørn; Berge, Rolf Kristian; Gerstoft, Jan; Ullum, Henrik; Trøseid, Marius; Nielsen, Susanne Dam

    2017-03-29

    Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD. Cross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine-N-oxide (TMAO), a microbiota-dependent, pro-atherogenic marker was measured using stable isotope dilution LC/MS/MS. The percentage of HIV + T2D+, HIV + T2D-, HIV-T2D+, and HIV-T2D- with hsCRP above cut-off was 50%, 19%, 47%, and 11%, respectively. HIV + T2D+ had elevated ADMA (0.67 μM (0.63-0.72) compared to HIV + T2D- (0.60 μM (0.57-0.64) p = 0.017), HIV-T2D+ (0.57 μM (0.51-63) p = 0.008), and HIV-T2D- (0.55 μM (0.52-0.58) p inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute to endothelial dysfunction. Whether gut microbiota is a contributing factor to this remains to be determined.

  5. Circumcision status and incident herpes simplex virus type 2 infection, genital ulcer disease, and HIV infection

    Science.gov (United States)

    Mehta, Supriya D.; Moses, Stephen; Parker, Corette B.; Agot, Kawango; Maclean, Ian; Bailey, Robert C.

    2013-01-01

    Objective We assessed the protective effect of medical male circumcision (MMC) against HIV, herpes simplex virus type 2 (HSV-2), and genital ulcer disease (GUD) incidence. Design Two thousand, seven hundred and eighty-seven men aged 18–24 years living in Kisumu, Kenya were randomly assigned to circumcision (n=1391) or delayed circumcision (n =1393) and assessed by HIV and HSV-2 testing and medical examinations during follow-ups at 1, 3, 6, 12, 18, and 24 months. Methods Cox regression estimated the risk ratio of each outcome (incident HIV, GUD, HSV-2) for circumcision status and multivariable models estimated HIV risk associated with HSV-2, GUD, and circumcision status as time-varying covariates. Results HIV incidence was 1.42 per 100 person-years. Circumcision was 62% protective against HIV [risk ratio =0.38; 95% confidence interval (CI) 0.22–0.67] and did not change when controlling for HSV-2 and GUD (risk ratio =0.39; 95% CI 0.23–0.69). GUD incidence was halved among circumcised men (risk ratio =0.52; 95% CI 0.37–0.73). HSV-2 incidence did not differ by circumcision status (risk ratio =0.94; 95% CI 0.70–1.25). In the multivariable model, HIV seroconversions were tripled (risk ratio =3.44; 95% CI 1.52–7.80) among men with incident HSV-2 and seven times greater (risk ratio =6.98; 95% CI 3.50–13.9) for men with GUD. Conclusion Contrary to findings from the South African and Ugandan trials, the protective effect of MMC against HIV was independent of GUD and HSV-2, and MMC had no effect on HSV-2 incidence. Determining the causes of GUD is necessary to reduce associated HIV risk and to understand how circumcision confers protection against GUD and HIV PMID:22382150

  6. Direct Phenotypical and Functional Dysregulation of Primary Human B Cells by Human Immunodeficiency Virus (HIV) Type 1 In Vitro

    OpenAIRE

    Ana Judith Perisé-Barrios; María Ángeles Muñoz-Fernandez; Marjorie Pion

    2012-01-01

    BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. METHODS/PRINCIPAL FINDINGS: We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and pheno...

  7. Quality Control Assessment of Human Immunodeficiency Virus Type 2 (HIV-2) Viral Load Quantification Assays: Results from an International Collaboration on HIV-2 Infection in 2006▿

    Science.gov (United States)

    Damond, Florence; Benard, Antoine; Ruelle, Jean; Alabi, Abraham; Kupfer, Bernd; Gomes, Perpetua; Rodes, Berta; Albert, Jan; Böni, Jürg; Garson, Jeremy; Ferns, Bridget; Matheron, Sophie; Chene, Geneviève; Brun-Vezinet, Françoise

    2008-01-01

    Human immunodeficiency virus type 2 (HIV-2) RNA quantification assays used in nine laboratories of the ACHIEV2E (A Collaboration on HIV-2 Infection) study group were evaluated. In a blinded experimental design, laboratories quantified three series of aliquots of an HIV-2 subtype A strain, each at a different theoretical viral load. Quantification varied between laboratories, and international standardization of quantification assays is strongly needed. PMID:18434556

  8. Morphologic magnetic resonance imaging features of therapy-induced cerebral necrosis.

    Science.gov (United States)

    Rogers, L R; Gutierrez, J; Scarpace, L; Schultz, L; Ryu, S; Lord, B; Movsas, B; Honsowetz, J; Jain, R

    2011-01-01

    To describe the morphologic magnetic resonance imaging (MRI) findings in histologically proven therapy-induced cerebral necrosis. We retrospectively reviewed the morphologic MRI findings in patients with therapy-induced cerebral necrosis. Images were reviewed for size, location, and characteristics of signal intensity abnormalities and T1-contrast enhancement. Images were also assessed for mass effect, necrosis, cyst, atrophy, cortical thinning, and leukoencephalopathy. The individual imaging characteristics were correlated with clinical and treatment variables. There were 44 patients. Seventy percent had a glioma, all patients had received radiation, and 57% had received chemotherapy in close proximity to radiation. All images demonstrated contrast enhancement, predominantly in the white matter. Enhancement was present in the periventricular/subependymal region in 50% of cases and the corpus callosum in 27%. The most common pattern of lesion peripheral enhancement was "spreading wavefront" and of interior enhancement was "Swiss cheese/soap bubble." The enhancing lesion was single in 60% of cases. Mass effect was present in 93% of patients. Location and patterns of enhancement were significantly associated with the interval from brain radiation to the diagnosis of therapy-induced cerebral necrosis, tumor histology, patient age, type of radiation, and administration of systemic chemotherapy. This is the largest study of the morphologic conventional MRI findings in pathologically confirmed therapy-induced cerebral necrosis. We characterized the imaging findings in a variety of tumor types following a variety of radiation treatments and other antineoplastic therapy. These findings may be of value in identifying therapy-induced cerebral necrosis in patients treated for a brain tumor.

  9. Metabolic dysregulation and interventions in type 2 diabetes mellitus and HIV-lipodystrophy

    NARCIS (Netherlands)

    Wijk, J.P.H. van

    2005-01-01

    The focus of this thesis is on two aspects of metabolic dysregulation, type 2 diabetes mellitus and HIV-lipodystrophy, and the effects of insulin-sensitizing agents. Thiazolidinediones (TZDs) have received increasing attenttion for the treatment of hyperglycemia in type 2 diabetes. Currently,

  10. Sensing of HIV-1 Entry Triggers a Type I Interferon Response in Human Primary Macrophages.

    Science.gov (United States)

    Decalf, Jérémie; Desdouits, Marion; Rodrigues, Vasco; Gobert, François-Xavier; Gentili, Matteo; Marques-Ladeira, Santy; Chamontin, Célia; Mougel, Marylène; Cunha de Alencar, Bruna; Benaroch, Philippe

    2017-08-01

    Along with CD4(+) T lymphocytes, macrophages are a major cellular source of HIV-1 replication and a potential viral reservoir. Following entry and reverse transcription in macrophages, cloaking of the viral cDNA by the HIV-1 capsid limits its cytosolic detection, enabling efficient replication. However, whether incoming HIV-1 particles are sensed by macrophages prior to reverse transcription remains unclear. Here, we show that HIV-1 triggers a broad expression of interferon (IFN)-stimulated genes (ISG) in monocyte-derived macrophages within a few hours after infection. This response does not require viral reverse transcription or the presence of HIV-1 RNA within particles, but viral fusion is essential. This response is elicited by viruses carrying different envelope proteins and thus different receptors to proceed for viral entry. Expression of ISG in response to viral entry requires TBK1 activity and type I IFNs signaling. Remarkably, the ISG response is transient but affects subsequent viral spread. Together, our results shed light on an early step of HIV-1 sensing by macrophages at the level of entry, which confers an early protection through type I IFN signaling and has potential implications in controlling the infection.IMPORTANCE HIV infection is restricted to T lymphocytes and macrophages. HIV-1-infected macrophages are found in many tissues of infected patients, even under antiretroviral therapy, and are considered a viral reservoir. How HIV-1 is detected and what type of responses are elicited upon sensing remain in great part elusive. The kinetics and localization of the production of cytokines such as interferons in response to HIV is of critical importance to understanding how the infection and the immune response are established. Our study provides evidence that macrophages can detect HIV-1 as soon as it enters the cell. Interestingly, this sensing is independent of the presence of viral nucleic acids within the particles but requires their fusion

  11. Immunological predictors of survival in HIV type 2-infected rural villagers in Guinea-Bissau

    DEFF Research Database (Denmark)

    Jaffar, Shabbar; Van der Loeff, Maarten Schim; Eugen-Olsen, Jesper

    2005-01-01

    We investigated the association between beta2-microglobulin, neopterin, serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), CD4 count, and plasma viremia with survival in 133 HIV-2-infected villagers and 160 controls living in rural Guinea-Bissau. Subjects were recruited...... in 1991 and visited at home every 3-6 months until 1998. Median beta2-microglobulin, neopterin, and suPAR were significantly higher and CD4% significantly lower among HIV-2-infected individuals than controls. Thirty-one HIV-2-infected individuals died and 7 were lost to follow-up. beta2-Microglobulin, CD4......%, and plasma viral load were associated independently with survival in multivariate analyses. Neopterin and suPAR did not reach statistical significance. These findings suggest that immune activation is central to the pathogenesis of HIV. They also have important implications for resource-poor settings where...

  12. HIV-1 replication in the central nervous system occurs in two distinct cell types.

    Directory of Open Access Journals (Sweden)

    Gretja Schnell

    2011-10-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection of the central nervous system (CNS can lead to the development of HIV-1-associated dementia (HAD. We examined the virological characteristics of HIV-1 in the cerebrospinal fluid (CSF of HAD subjects to explore the association between independent viral replication in the CNS and the development of overt dementia. We found that genetically compartmentalized CCR5-tropic (R5 T cell-tropic and macrophage-tropic HIV-1 populations were independently detected in the CSF of subjects diagnosed with HIV-1-associated dementia. Macrophage-tropic HIV-1 populations were genetically diverse, representing established CNS infections, while R5 T cell-tropic HIV-1 populations were clonally amplified and associated with pleocytosis. R5 T cell-tropic viruses required high levels of surface CD4 to enter cells, and their presence was correlated with rapid decay of virus in the CSF with therapy initiation (similar to virus in the blood that is replicating in activated T cells. Macrophage-tropic viruses could enter cells with low levels of CD4, and their presence was correlated with slow decay of virus in the CSF, demonstrating a separate long-lived cell as the source of the virus. These studies demonstrate two distinct virological states inferred from the CSF virus in subjects diagnosed with HAD. Finally, macrophage-tropic viruses were largely restricted to the CNS/CSF compartment and not the blood, and in one case we were able to identify the macrophage-tropic lineage as a minor variant nearly two years before its expansion in the CNS. These results suggest that HIV-1 variants in CSF can provide information about viral replication and evolution in the CNS, events that are likely to play an important role in HIV-associated neurocognitive disorders.

  13. HPV types, HIV and invasive cervical carcinoma risk in Kampala, Uganda: a case-control study

    Directory of Open Access Journals (Sweden)

    Kleter Bernhard

    2011-06-01

    Full Text Available Abstract Background While the association of human papillomavirus (HPV with cervical cancer is well established, the influence of HIV on the risk of this disease in sub-Saharan Africa remains unclear. To assess the risk of invasive cervical carcinoma (ICC associated with HIV and HPV types, a hospital-based case-control study was performed between September 2004 and December 2006 in Kampala, Uganda. Incident cases of histologically-confirmed ICC (N=316 and control women (N=314, who were visitors or care-takers of ICC cases in the hospital, were recruited. Blood samples were obtained for HIV serology and CD4 count, as well as cervical samples for HPV testing. HPV DNA detection and genotyping was performed using the SPF10/DEIA/LiPA25 technique which detects all mucosal HPV types by DEIA and identifies 25 HPV genotypes by LiPA version 1. Samples that tested positive but could not be genotyped were designated HPVX. Odds ratios (OR and 95% confidence intervals (CI were calculated by logistic regression, adjusting for possible confounding factors. Results For both squamous cell carcinoma (SCC and adenocarcinoma of the cervix, statistically significantly increased ORs were found among women infected with HPV, in particular single HPV infections, infections with HPV16-related types and high-risk HPV types, in particular HPV16, 18 and 45. For other HPV types the ORs for both SCC and adenocarcinoma were not statistically significantly elevated. HIV infection and CD4 count were not associated with SCC or adenocarcinoma risk in our study population. Among women infected with high-risk HPV types, no association between HIV and SCC emerged. However, an inverse association with adenocarcinoma was observed, while decrease in CD4 count was not associated with ICC risk. Conclusions The ORs for SCC and adenocarcinoma were increased in women infected with HPV, in particular single HPV infections, infections with HPV16- and 18-related types, and high-risk HPV types

  14. Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation

    DEFF Research Database (Denmark)

    Yusim, K.; Kesmir, Can; Gaschen, B.

    2002-01-01

    The human cytotoxic T-lymphocyte (CTL) response to human immunodeficiency virus type 1 (HIV-1) has been intensely studied, and hundreds of CTL epitopes have been experimentally defined, published, and compiled in the HIV Molecular Immunology Database. Maps of CTL epitopes on HIV-1 protein sequences...... reveal that defined epitopes tend to cluster. Here we integrate the global sequence and immunology databases to systematically explore the relationship between HIV-1 amino acid sequences and CTL epitope distributions. CTL responses to five HIV-1 proteins, Gag p17, Gag p24, reverse transcriptase (RT), Env......, and Nef, have been particularly well characterized in the literature to date. Through comparing CTL epitope distributions in these five proteins to global protein sequence alignments, we identified distinct characteristics of HIV amino acid sequences that correlate with CTL epitope localization. First...

  15. Type 2 lepra reaction with HIV1 co-infection: a case report with interesting management implications.

    Science.gov (United States)

    Sachdeva, S; Amin, S S; Qaisar, S

    2011-01-01

    A patient co-infected with leprosy and Human Immunodeficiency Virus (HIV)-type 1 who developed type 2 lepra reaction in the absence of antiretroviral therapy is presented. The reaction responded only after initiating anti retroviral therapy (ART) despite normal CD4+ counts. The present report suggests that type 2 reactions in leprosy and HIV co-infected patients may not always be the typical manifestation of immune reconstitution inflammatory syndrome (IRIS) and stresses the importance of considering concomitant HIV infection in refractory lepra reactions. Extensive research is required into the manifestations of HIV in leprosy patients.

  16. Prevalence of HIV, human papillomavirus type 16 and herpes simplex virus type 2 among female sex workers in Guinea and associated factors.

    Science.gov (United States)

    Aho, Joséphine; Koushik, Anita; Coutlée, François; Diakité, Soumaïla Laye; Rashed, Sélim

    2014-03-01

    Female sex workers are at high risk for HIV infection. Sexually transmitted infections are known to be co-factors for HIV infection. Our aims were (1) to assess the prevalence of HIV and other sexually transmitted infections in this population; (2) to determine the association between sociodemographic characteristics, behavioural variables, and variables related to HIV prevention and HIV infection. A cross-sectional study was conducted in Conakry, Guinea, among a convenience sample of 223 female sex workers. A questionnaire on sociodemographic characteristics, risk factors, and exposure to prevention was administered. Screening for HIV, herpes simplex virus type 2, human papillomavirus type 16, Neisseria gonorrhoeae, and Chlamydia trachomatis was performed. Prevalences of HIV, herpes simplex virus type 2, human papillomavirus type 16, N. gonorrhoeae, and C. trachomatis were 35.3%, 84.1%, 12.2%, 9.0%, and 13.6%, respectively. Having a child, lubricant use, and human papillomavirus type 16 infection were associated with HIV infection. Interventions that promote screening and treatment of sexually transmitted infections are needed in order to achieve successful interventions to prevent HIV among female sex workers in resource-limited settings.

  17. HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

    DEFF Research Database (Denmark)

    Hove-Skovsgaard, Malene; Gaardbo, Julie Christine; Kolte, Lilian

    2017-01-01

    BACKGROUND: Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may...... without T2D (HIV-T2D-)). Groups were matched on age and sex. High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine.......001), which was mainly driven by a close correlation in HIV + T2D+ (rs = 0.63, p = 0.001). CONCLUSION: Elevated inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute...

  18. An HIV type 2 case series in Italy: a phylogenetic analysis.

    Science.gov (United States)

    D'Ettorre, Gabriella; Lo Presti, Alessandra; Gori, Caterina; Cella, Eleonora; Bertoli, Ada; Vullo, Vincenzo; Perno, Carlo Federico; Ciotti, Marco; Foley, Brian T; Ciccozzi, Massimo

    2013-09-01

    In recent years, the increase of migration from countries where human immunodeficiency virus type 2 (HIV-2) is endemic to industrialized countries has facilitated the spread of the virus in individuals previously unexposed to this threat. In this report, we performed a phylogenetic analysis on pol and env sequences of HIV-2 strains identified in foreigners and native citizens to trace the origin of infection. All but one of the 17 pol gene sequences were classified as group A. HIV-2 strains were aggregated in several clusters depending by the country of origin and/or infection. One patient (1AA) was classified as being infected with a recombinant between HIV-2 group A and HIV-2 group B, because the pol gene sequence was clearly in the group A, but an env V3 region sequence from this patient was more similar to group B viruses. Therefore, it is urgent to strengthen the surveillance and use adequate molecular virological tools to diagnose and monitor HIV-2 infection.

  19. Acquisition of GB Virus Type C and Lower Mortality in Patients With Advanced HIV Disease

    Science.gov (United States)

    Vahidnia, Farnaz; Petersen, Maya; Stapleton, Jack T.; Rutherford, George W.; Busch, Michael; Custer, Brian

    2012-01-01

    Background. GB virus type C (GBV-C) is transmitted by sexual or parenteral exposure and is prevalent among patients receiving blood products. GBV-C is associated with lower human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. Open questions are the presence and the direction of any causal relationship between GBV-C infection and HIV disease markers in the context of highly active antiretroviral therapy (HAART). Methods. We used a limited access database obtained from the National Heart, Lung, and Blood Institute's Viral Activation Transfusion Study (VATS), a randomized controlled trial of leukoreduced vs nonleukoreduced transfusions to HIV-infected transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers. Cox regression models and inverse probability of treatment weights were used to examine the association between GBV-C coinfection and mortality in the VATS cohort. Results. We found a significant reduction in mortality among GBV-C coinfected VATS subjects, after adjusting for HAART status, HIV RNA level, and CD4 cell count at baseline. Acquisition of GBV-C RNA (n = 39) was associated with lower mortality in 294 subjects who were GBV-C negative at baseline, adjusting for baseline covariates (hazard ratio = 0.22, 95% confidence interval [CI]: .08–.58) and in models in which weights were used to control for time-updated covariates (odds ratio = 0.21, 95% CI: .08–.60). Conclusions. GBV-C viremia is associated with lower mortality, and GBV-C acquisition via transfusion is associated with a significant reduction in mortality in HIV-infected individuals, controlling for HIV disease markers. These findings provide the first evidence that incident GBV-C infection alters mortality in HIV-infected patients. PMID:22752515

  20. Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120

    DEFF Research Database (Denmark)

    Lund, O S; Losman, B; Schønning, Kristian

    1998-01-01

    -fold. When the same ratio of plasmids was tested in COS-1 cells the inhibition of HIV-1 was an order of magnitude less than observed in 293 cells. COS-1 and 293 cells differed in that only 293 cells displayed saturation of virus production with respect to the envelope protein. Our data fit a simple......An amino acid substitution (D --> K) in the C3 region of HIV-1 gp120 has previously been shown to inhibit binding of virions to CD4+ cells. We have introduced the same mutation into the HIV-1 isolate LAV-I(BRU), in which the mutation is denoted D373K. Here we show that the D373K envelope protein...... is processed and incorporated into virus particles, but that D373K virions have no detectable infectivity (below 0.1% relative to wild type). When D373K and the wild-type envelope gene were cotransfected in 293 cells at a 4:1 ratio, the resultant infectivity of the HIV-1 supernatant was reduced more than 100...

  1. Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120

    DEFF Research Database (Denmark)

    Lund, O S; Losman, B; Schønning, Kristian

    1998-01-01

    An amino acid substitution (D --> K) in the C3 region of HIV-1 gp120 has previously been shown to inhibit binding of virions to CD4+ cells. We have introduced the same mutation into the HIV-1 isolate LAV-I(BRU), in which the mutation is denoted D373K. Here we show that the D373K envelope protein......-fold. When the same ratio of plasmids was tested in COS-1 cells the inhibition of HIV-1 was an order of magnitude less than observed in 293 cells. COS-1 and 293 cells differed in that only 293 cells displayed saturation of virus production with respect to the envelope protein. Our data fit a simple...... is processed and incorporated into virus particles, but that D373K virions have no detectable infectivity (below 0.1% relative to wild type). When D373K and the wild-type envelope gene were cotransfected in 293 cells at a 4:1 ratio, the resultant infectivity of the HIV-1 supernatant was reduced more than 100...

  2. Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of human blood monocytes and peritoneal macrophages.

    OpenAIRE

    Shadduck, P P; Weinberg, J B; Haney, A. F.; Bartlett, J. A.; Langlois, A J; Bolognesi, D P; Matthews, T J

    1991-01-01

    The influence of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of freshly isolated normal human peritoneal macrophages and blood monocytes was examined. Each of 14 HIV antibody-positive human serum samples was found to block the infection of four virus isolates (human T-cell lymphotropic virus type IIIBa-L [HTLV-IIIBa-L], HTLV-IIIB, D.U. 6587-7, and D.U. 7887-8) at serum dilutions ranging from 10(-1) to 10(-2). Three of these isolates (HTLV-IIIBa-L, D.U. 6...

  3. Human Immunodeficiency Virus-Type 1 (HIV-1) and the Brain.

    Science.gov (United States)

    Grant, Igor; Heaton, Robert K.

    1990-01-01

    Provides update on what is currently known about neurobehavioral correlates of infection with human immunodeficiency virus-Type 1 (HIV-1), causative agent of acquired immunodeficiency syndrome. Discusses methodological and theoretical issues complicating interpretation of existing data and suggests strategies for future research in this area. (NB)

  4. Antiviral Functions of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific IgG Antibodies: Effects of Antiretroviral Therapy and Implications for Therapeutic HIV-1 Vaccine Design.

    Science.gov (United States)

    French, Martyn A; Tjiam, M Christian; Abudulai, Laila N; Fernandez, Sonia

    2017-01-01

    Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection. However, production of IgG antibodies with virus neutralizing activity by vaccination remains problematic and while vaccine-induced natural killer cell-activating IgG antibodies have been shown to prevent the acquisition of HIV-1 infection, they may not be sufficient to control or eradicate established HIV-1 infection. It is, therefore, important to consider other functional characteristics of IgG antibody responses. IgG antibodies to viruses also mediate opsonophagocytic antibody responses against virions and capsids that enhance the function of phagocytic cells playing critical roles in antiviral immune responses, particularly conventional dendritic cells and plasmacytoid dendritic cells. Emerging evidence suggests that these antibody functions might contribute to the control of HIV-1 infection. In addition, IgG antibodies contribute to the intracellular degradation of viruses via binding to the cytosolic fragment crystallizable (Fc) receptor tripartite motif containing-21 (TRIM21). The functional activity of an IgG antibody response is influenced by the IgG subclass content, which affects binding to antigens and to Fcγ receptors on phagocytic cells and to TRIM21. The IgG subclass content and avidity of IgG antibodies is determined by germinal center (GC) reactions in follicles of lymphoid tissue

  5. Effect of Different Types of Exercise in HIV + Mozambican Women Using Antiretroviral Therapy

    OpenAIRE

    Mangona, Luc?lia; Daca, Tim?teo; Tchonga, Francisco; Bule, Odete; Bhatt, Nilesh; Jani, Ilesh; Damasceno, Albertino; Prista, Ant?nio

    2015-01-01

    The aim of this study was to evaluate and compare the effect of two types of exercises interventions on the regularity and health-related physical fitness in HIV-infected individuals who use antiretroviral therapy (ART). A total of 53 HIV+ African women (mean age=39.5?8.4 years) on ART participated in the study. Subjects were randomly divided into 3 groups, namely, formal exercise (FEG), playful exercise (PEG) and control (CG). During 12 weeks, the exercise groups underwent a program of 1-hou...

  6. Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection

    Science.gov (United States)

    Cheng, Liang; Yu, Haisheng; Li, Guangming; Li, Feng; Ma, Jianping; Li, Jingyun; Chi, Liqun; Zhang, Liguo

    2017-01-01

    The direct link between sustained type I interferon (IFN-I) signaling and HIV-1–induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/β receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1–induced aberrant immune activation. Surprisingly, IFNAR blockade rescued both total human T cell and HIV-specific T cell numbers despite elevated HIV-1 replication and immune activation. We showed that IFNAR blockade reduced HIV-1–induced apoptosis of CD4+ T cells. Importantly, IFNAR blockade also rescued the function of human T cells, including HIV-1–specific CD8+ and CD4+ T cells. We conclude that during persistent HIV-1 infection, IFN-Is suppress HIV-1 replication, but contribute to depletion and dysfunction of T cells. PMID:28614789

  7. Cognitive Consequences of a Sustained Monocyte Type 1 IFN Response in HIV-1 Infection

    OpenAIRE

    Pulliam, Lynn

    2014-01-01

    With successful antiretroviral therapy, HIV-1-infected subjects can achieve undetectable peripheral viral loads and immune homeostasis. However, in a subset of individuals on therapy, peripheral monocytes have a gene expression profile characteristic of a type 1 interferon α (IFN) response. This type 1 IFN response correlates with a number of pathogenic conditions including neural cell injury and in combination with HCV infection, cognitive impairment. Lessons from the non-human primate model...

  8. Robust supervised and unsupervised statistical learning for HIV type 1 coreceptor usage analysis.

    Science.gov (United States)

    Prosperi, Mattia C F; Fanti, Iuri; Ulivi, Giovanni; Micarelli, Alessandro; De Luca, Andrea; Zazzi, Maurizio

    2009-03-01

    Human immunodeficiency virus type 1 (HIV-1) isolates differ in their use of coreceptors to enter target cells. This has important implications for both viral pathogenicity and susceptibility to entry inhibitors, recently approved or under development. Predicting HIV-1 coreceptor usage on the basis of sequence information is a challenging task, due to the high variability of the envelope. The associations of the whole HIV-1 envelope genetic features (subtype, mutations, insertions-deletions, physicochemical properties) and clinical markers (viral RNA load, CD8(+), CD4(+) T cell counts) with viral tropism were investigated, using a set of 2896 (659 after filter, 593 patients) sequence-tropism pairs available at the Los Alamos HIV database. Bootstrapped hierarchical clustering was used to assess mutational covariation. Univariate and multivariate analysis was performed to assess the relative importance of different features. Different machine learning (logistic regression, support vector machines, decision trees, rule bases, instance based reasoning) and feature selection (filter and embedded) methods, along with loss functions (accuracy, AUC of ROC curves, sensitivity, specificity, f-measure), were applied and compared for the classification of X4 variants. Extra-sample error estimation was assessed via multiple cross-validation and adjustments for multiple testing. A high-performing, compact, and interpretable logistic regression model was derived to infer HIV-1 coreceptor tropism for a given patient [accuracy = 92.76 (SD 3.07); AUC = 0.93 (SD 0.04)].

  9. 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 ...

  10. 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.

  11. RNA-interference-based gene therapy approaches to HIV type-1 treatment: tackling the hurdles from bench to bedside

    NARCIS (Netherlands)

    Von Eije, Karin J.; Berkhout, Ben

    2009-01-01

    RNA interference (RNAi) is a cellular mechanism that can be induced by small interfering RNAs (siRNAs) to mediate sequence-specific gene silencing by cleavage of the targeted messenger RNA. RNAi can be used as an antiviral approach to silence HIV type-1 (HIV-1) through stable expression of

  12. Low level viremia and high CD4% predict normal survival in a cohort of HIV type-2-infected villagers

    NARCIS (Netherlands)

    Berry, Neil; Jaffar, Shabbar; Schim van der Loeff, Maarten; Ariyoshi, Koya; Harding, Elizabeth; N'Gom, Pa Tamba; Dias, Francisco; Wilkins, Andrew; Ricard, Dominic; Aaby, Peter; Tedder, Richard; Whittle, Hilton

    2002-01-01

    A community-based study of human immunodeficiency virus type 2 (HIV-2) infection was conducted in a rural village in northern Guinea Bissau, West Africa to assess the relationship between plasma HIV-2 RNA levels, CD4 lymphocyte percentage, and survival over an 8-year period. The cohort of 133

  13. How partnership type and HIV seroconcordance affect HIV transmission risk in regular sexual partnerships: a cross-sectional survey of Australian gay and bisexual men.

    Science.gov (United States)

    Bavinton, Benjamin R; Grulich, Andrew E; Duncan, Duane; Zablotska, Iryna B; Prestage, Garrett P

    2017-06-22

    Background: Regular sexual partnerships among gay and bisexual men (GBM) who practice condomless anal intercourse (CLAI) have not been well characterised in terms of partnership type, HIV seroconcordance and risk of HIV transmission. Primarily sexual regular partnerships, although commonly reported by gay men, have largely been ignored in research and HIV prevention. Among regular partners reporting CLAI with each other, we determined factors differentiating romantic or committed relationships from partnerships organised primarily around sex ('fuckbuddies') and estimated the proportion of CLAI presenting risk for HIV transmission. Methods: An online, cross-sectional survey of Australian GBM was conducted. Univariate and multivariate generalised estimating equations were used to determine statistical associations. Results: Men reported on 2250 regular sexual partnerships. Over half the partnerships were romantic or committed relationships. Over half the partnerships were HIV-negative seroconcordant (54.9%), 3.1% were HIV-positive seroconcordant, 5.2% were serodiscordant and 36.8% were of unknown seroconcordance. Potential risks presented by CLAI were sometimes mitigated by protective factors, such as having a clear spoken agreement about sex with outside partners, having fewer outside partners, openly discussing HIV risk and having an agreement to reduce risk from outside partners. These protective factors were more often found in romantic or committed relationships than among primarily sexual partnerships, and were less often found in partnerships of unknown seroconcordance. Conclusion: CLAI is more common among regular sexual partnerships considered to be of a romantic, committed nature. However, factors associated with such romantic or committed partnerships can also protect against HIV transmission risk. Unknown seroconcordance, particularly lack of communication about HIV status among primarily sexual partnerships, is a key risk factor that needs to be

  14. 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.

  15. The influence of HLA-types on disease progression among HIV-2 infected patients in Guinea-Bissau

    DEFF Research Database (Denmark)

    Thomsen, Ditte; Erikstrup, Christian; Jespersen, Sanne

    2018-01-01

    OBJECTIVES: HIV-2 is endemic in West Africa and is characterized by lower transmissibility due to lower viral load, and HIV-2 infected persons usually have a slower progression to AIDS. The mechanisms behind the slower disease progression are unknown. The main objective was to identify specific HLA......: The three alleles HLA-B58:01, HLA-DPB110:01 and HLA-DRB111:01 may protect against HIV-2 disease progression towards AIDS....... class I and II alleles that may influence the disease progression of HIV-2 infection. DESIGN: Cohort follow-up study. METHODS: We used high resolution HLA typing of DNA from 437 antiretroviral treatment naïve HIV-2 infected patients from the Bissau HIV Cohort, Guinea-Bissau, to identify HLA alleles...

  16. Induction of antibodies against epitopes inaccessible on the HIV type 1 envelope oligomer by immunization with recombinant monomeric glycoprotein 120

    DEFF Research Database (Denmark)

    Schønning, Kristian; Bolmstedt, A; Novotny, J

    1998-01-01

    to elicit antibodies preferentially neutralizing mutant variants of HIV-BRU lacking the N306 glycan. Therefore, two guinea pigs were immunized with monomeric wild-type HIV-BRU gp120 possessing the N306 glycan and immune sera were tested for neutralization against target viruses HIV-BRU, -A308, and -A308T321....... HIV-A308 and HIV-A308T321 lack the N306 glycan; HIV-A308T321 contains an additional mutation at the tip of V3 rendering it resistant to MAb binding at this epitope. Both immune sera preferentially neutralized the two mutant virus variants lacking the N306 glycan, with a 10- to 20-fold increase...

  17. Women with HIV are more commonly infected with non-16 and -18 high-risk HPV types.

    Science.gov (United States)

    McKenzie, Nathalie Dauphin; Kobetz, Erin N; Hnatyszyn, James; Twiggs, Leo B; Lucci, Joseph A

    2010-03-01

    To review and summarize evidence from clinical, translational and epidemiologic studies which have examined the clinically relevant aspects of HPV type prevalence and cervical dysplasia in HIV-infected women. Relevant studies were identified through a MEDLINE search. References of identified reports were also used to identify additional published articles for review. HIV-infected women in different geographic regions (such as Zambia, Brazil, Rochester NY) appear to be infected with less prevalent types of HR-HPV as compared to the general population who, across all continents, are more commonly infected with types 16 and 18. Secondly, integration of HPV DNA into the host genome is no longer thought to be a necessary cause of malignant transformation of cervical cells. However, rate of integration appears to differ by the type of HPV. In fact, the types of HPV which appear to be more common in cervical dysplasia of HIV-infected women are the same types which are more likely to require integration for malignant transformation. Finally, HPV types found in HIV-infected women are relatively common and likely to persist. The most common among these types belong to the alpha-9 and -7 species which are the most carcinogenic species. Given that current vaccines target HR-HPV-16/18, the findings from the above mentioned studies may have important implications for the design of HPV vaccines that target the types of HPV associated with disease risk in HIV-infected women. HPV typing and assessment of the physical state (whether it is integrated or episomal) appear to be two valuable parameters for the prognostic evaluation of dysplastic lesions of the uterine cervix. This, however, has not yet been assessed in HIV-infected women. Recent data about the immune response in HPV/HIV co-infection may lead to understanding potential mechanisms for less virulent HPV causing malignant transformation in HIV-infected women.

  18. Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration.

    Science.gov (United States)

    Azzoni, Livio; Foulkes, Andrea S; Papasavvas, Emmanouil; Mexas, Angela M; Lynn, Kenneth M; Mounzer, Karam; Tebas, Pablo; Jacobson, Jeffrey M; Frank, Ian; Busch, Michael P; Deeks, Steven G; Carrington, Mary; O'Doherty, Una; Kostman, Jay; Montaner, Luis J

    2013-01-15

    Antiretroviral therapy (ART)-mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication. A total of 23 HIV type 1 (HIV-1)-infected, virologically suppressed subjects receiving ART (CD4(+) T-cell count, >450 cells/μL) were randomly assigned to have 180 μg/week (for arm A) or 90 μg/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg-interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, ≥ 400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed. At week 12 of Peg-interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication. NCT00594880.

  19. SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2.

    Science.gov (United States)

    Buckheit, R W; Watson, K; Fliakas-Boltz, V; Russell, J; Loftus, T L; Osterling, M C; Turpin, J A; Pallansch, L A; White, E L; Lee, J W; Lee, S H; Oh, J W; Kwon, H S; Chung, S G; Cho, E H

    2001-02-01

    We have identified and characterized a potent new nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) that also is active against HIV-2 and which interferes with virus replication by two distinct mechanisms. 1-(3-Cyclopenten-1-yl)methyl-6-(3,5-dimethylbenzoyl)-5-ethyl-2,4-pyrimidinedione (SJ-3366) inhibits HIV-1 replication at concentrations of approximately 1 nM, with a therapeutic index of greater than 4 x 10(6). The efficacy and toxicity of SJ-3366 are consistent when evaluated with established or fresh human cells, and the compound is equipotent against all strains of HIV-1 evaluated, including syncytium-inducing, non-syncytium-inducing, monocyte/macrophage-tropic, and subtype virus strains. Distinct from other members of the pharmacologic class of NNRTIs, SJ-3366 inhibited laboratory and clinical strains of HIV-2 at a concentration of approximately 150 nM, yielding a therapeutic index of approximately 20,000. Like most NNRTIs, the compound was less active when challenged with HIV-1 strains possessing the Y181C, K103N, and Y188C amino acid changes in the RT and selected for a virus with a Y181C amino acid change in the RT after five tissue culture passages in the presence of the compound. In combination anti-HIV assays with nucleoside and nonnucleoside RT and protease inhibitors, additive interactions occurred with all compounds tested with the exception of dideoxyinosine, with which a synergistic interaction was found. Biochemically, SJ-3366 exhibited a K(i) value of 3.2 nM, with a mixed mechanism of inhibition against HIV-1 RT, but it did not inhibit HIV-2 RT. SJ-3366 also inhibited the entry of both HIV-1 and HIV-2 into target cells. On the basis of its therapeutic index and multiple mechanisms of anti-HIV action, SJ-3366 represents an exciting new compound for use in HIV-infected individuals.

  20. Cognitive consequences of a sustained monocyte type 1 IFN response in HIV-1 infection.

    Science.gov (United States)

    Pulliam, Lynn

    2014-01-01

    With successful antiretroviral therapy, HIV-1-infected subjects can achieve undetectable peripheral viral loads and immune homeostasis. However, in a subset of individuals on therapy, peripheral monocytes have a gene expression profile characteristic of a type 1 interferon α (IFN) response. This type 1 IFN response correlates with a number of pathogenic conditions including neural cell injury and in combination with HCV infection, cognitive impairment. Lessons from the non-human primate models of pathogenic and nonpathogenic SIV suggest that returning the initial IFN spike in acute SIV infection to normal allows the immune system to control infection and return to homeostasis. An IFN "alarm" signature, defined as monocyte activation with overexpression of the type1 IFN genes IFI27 and CD169, would be useful for identifying a subset of subjects with HIV-1 infection that could progress to a number of pathologies associated with immune activation including cognitive dysfunction. This strategy is being actively pursued for autoimmune diseases that are characterized by an IFN signature. Therapies to block the IFN signature are under investigation as a means to reset the immune system and in a subset of HIV-1-infected subjects may be an adjuvant to standard antiviral therapy to return cognitive function.

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

    Directory of Open Access Journals (Sweden)

    Juanjuan Zhao

    2018-01-01

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

  2. Type-specific cervico-vaginal human papillomavirus infection increases risk of HIV acquisition independent of other sexually transmitted infections.

    Directory of Open Access Journals (Sweden)

    Karen K Smith-McCune

    2010-04-01

    Full Text Available Sexually transmitted infections (STIs such as herpes simplex virus (HSV-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.This prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18-49 years for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation. HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%, 16 (4.7%, 70 (2.4%, and 18 (2.3%. In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use, HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09-4.15 or HPV 70 (aHR 2.68; 95% CI 1.08-6.66. In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use, HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02-2.85, any oncogenic HPV type (aHR 1.96; 95% CI 1.16-3.30, HPV 31 (aHR 4.25; 95% CI 1.81-9.97 or HPV 70 (aHR 3.30; 95% CI 1.50-7.20. Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19-3.21 or excluded (aHR 1.96; 95% CI 1.02-2.85 from the analysis.Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were

  3. Association of TRIM22 with the type 1 interferon response and viral control during primary HIV-1 infection.

    OpenAIRE

    Singh Ravesh; Gaiha Gaurav; Werner Lise; McKim Kevin; Mlisana Koleka; Luban Jeremy; Walker Bruce D; Karim Salim S Abdool; Brass Abraham L; Ndung'u Thumbi; CAPRISA 002 Acute Infection Study Team

    2011-01-01

    Type 1 interferons (IFNs) induce the expression of the tripartite interaction motif (TRIM) family of E3 ligases but the contribution of these antiviral factors to HIV pathogenesis is not completely understood. We hypothesized that the increased expression of select type 1 IFN and TRIM isoforms is associated with a significantly lower likelihood of HIV 1 acquisition and viral control during primary HIV 1 infection. We measured IFN a IFN ß myxovirus resistance protein A (MxA) human TRIM5a (huTR...

  4. Association of TRIM22 with the Type 1 Interferon Response and Viral Control during Primary HIV-1 Infection▿

    OpenAIRE

    Singh, Ravesh; Gaiha, Gaurav; Werner, Lise; McKim, Kevin; Mlisana, Koleka; Luban, Jeremy; Bruce D. Walker; Karim, Salim S. Abdool; Brass, Abraham L; Ndung'u, Thumbi

    2010-01-01

    Type 1 interferons (IFNs) induce the expression of the tripartite interaction motif (TRIM) family of E3 ligases, but the contribution of these antiviral factors to HIV pathogenesis is not completely understood. We hypothesized that the increased expression of select type 1 IFN and TRIM isoforms is associated with a significantly lower likelihood of HIV-1 acquisition and viral control during primary HIV-1 infection. We measured IFN-α, IFN-β, myxovirus resistance protein A (MxA), human TRIM5α (...

  5. Response to "Rapid tests for HIV type discrimination in West Africa may perform differently"

    National Research Council Canada - National Science Library

    Tchounga, Boris K; Ekouevi, Didier K; Eholie, Serge P

    2015-01-01

    ... test used for the initial discrimination of HIV-positive patients. Our team previously conducted in 2004 a field evaluation of rapid HIV serologic tests in Cote d'Ivoire and highlighted the lower accuracy of Genie II for differentiating between HIV-1, HIV-2 and dually reactive patients [4]. In our most recent study, the initial HIV diagnostic te...

  6. Human papillomavirus prevalence and type distribution in 3603 HIV-positive and HIV-negative women in the general population of Tanzania

    DEFF Research Database (Denmark)

    Dartell, Myassa Arkam; Rasch, Vibeke; Kahesa, Crispin

    2012-01-01

    The aim of the Prevention of Cervical Cancer in Tanzania (PROTECT) study is to assess the prevalence of oncogenic human papillomavirus (HPV) and to determine the type distribution among women in the general population according to human immunodeficiency virus (HIV) status, in preparation for a po......The aim of the Prevention of Cervical Cancer in Tanzania (PROTECT) study is to assess the prevalence of oncogenic human papillomavirus (HPV) and to determine the type distribution among women in the general population according to human immunodeficiency virus (HIV) status, in preparation...

  7. Nevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single-Dose Nevirapine

    Science.gov (United States)

    Micek, Mark A.; Blanco, Ana Judith; Beck, Ingrid A.; Dross, Sandra; Matunha, Laurinda; Montoya, Pablo; Seidel, Kristy; Gantt, Soren; Matediane, Eduardo; Jamisse, Lilia; Gloyd, Stephen; Frenkel, Lisa M.

    2011-01-01

    Background In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection. Methods We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time. Results Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P =.006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P =.001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P =.017, compared with established in utero infection). Conclusions The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals. PMID:20384494

  8. Direct Phenotypical and Functional Dysregulation of Primary Human B Cells by Human Immunodeficiency Virus (HIV) Type 1 In Vitro

    Science.gov (United States)

    Perisé-Barrios, Ana Judith; Muñoz-Fernandez, María Ángeles; Pion, Marjorie

    2012-01-01

    Background Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. Methods/Principal Findings We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. Conclusion/Significance We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease. PMID:22768302

  9. Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression.

    Science.gov (United States)

    Hardy, Gareth A D; Sieg, Scott F; Rodriguez, Benigno; Jiang, Wei; Asaad, Robert; Lederman, Michael M; Harding, Clifford V

    2009-05-28

    Type I interferon (IFNalpha/beta) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNalpha/beta plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNalpha/beta in HIV-1 infection is poorly understood. We report significant defects in IFNalpha/beta receptor (IFNalpha/betaR) expression, IFNalpha signaling, and IFNalpha-induced gene expression in monocytes from HIV-1-infected subjects. IFNalpha/betaR expression correlated directly with CD4+ T-cell count and inversely with HIV-1 RNA level and expression of CD38 by memory (CD45RO+) CD8+ T cells, a measure of pathologic immune activation in HIV-1 infection associated with disease progression. In addition, monocytes from HIV-1-infected persons showed diminished responses to IFNalpha, including decreased induction of phosphorylated STAT1 and the classical interferon-stimulated gene produces MxA and OAS. These IFNalpha responses were decreased regardless of IFNalpha/betaR expression, suggesting that regulation of intracellular signaling may contribute to unresponsiveness to IFNalpha/beta in HIV-1 disease. Defective monocyte responses to IFNalpha/beta may play an important role in the pathogenesis of HIV-1 infection, and decreased IFNalpha/betaR expression may serve as a novel marker of disease progression.

  10. Direct phenotypical and functional dysregulation of primary human B cells by human immunodeficiency virus (HIV) type 1 in vitro.

    Science.gov (United States)

    Perisé-Barrios, Ana Judith; Muñoz-Fernandez, María Ángeles; Pion, Marjorie

    2012-01-01

    Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease.

  11. Direct phenotypical and functional dysregulation of primary human B cells by human immunodeficiency virus (HIV type 1 in vitro.

    Directory of Open Access Journals (Sweden)

    Ana Judith Perisé-Barrios

    Full Text Available BACKGROUND: Human immunodeficiency virus type 1 (HIV-1 induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. METHODS/PRINCIPAL FINDINGS: We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID mRNA that is responsible for class switch recombination (CSR and somatic hypermutation (SHM. Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. CONCLUSION/SIGNIFICANCE: We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease.

  12. HPV type infection in different anogenital sites among HIV-positive Brazilian women

    Directory of Open Access Journals (Sweden)

    Donadi Eduardo Antonio

    2008-03-01

    Full Text Available Abstract Objectives To evaluate the prevalence of human papillomavirus (HPV types, and risk factors for HPV positivity across cervix, vagina and anus, we conducted a study among 138 women with human immunodeficiency virus (HIV. Goal Compare the prevalence of different HPV types and the risk factors for HPV positivity in three sites. Results The most frequently detected HPV types in all sites were, in decreasing order, HPV16, 53, 18, 61 and 81. Agreement between the cervix and vagina was good (kappa 0.60 – 0.80 for HPV16 and 53 and excellent (Kappa > 0.80 for HPV18 and 61. HPV positivity was inversely associated with age for all combinations including the anal site. Conclusion In HIV positive women, HPV18 is the most spread HPV type found in combinations of anal and genital sites. The relationship of anal to genital infection has implications for the development of anal malignancies. Thus, the efficacy of the current HPV vaccine may be considered not only for the cervix, but also for prevention of HPV18 anal infection among immunossuppressed individuals.

  13. Fluorescently-labeled RNA packaging into HIV-1 particles: Direct examination of infectivity across central nervous system cell types

    Science.gov (United States)

    Xu, Ruqiang; El-Hage, Nazira; Dever, Seth M.

    2015-01-01

    HIV penetrates the central nervous system (CNS), and although it is clear that microglia and to a lesser extent astrocytes are infected, whether certain other cell types such as neurons are infected remains unclear. Here, we confirmed the finding that RNAs of both cellular and viral origins are present in native HIV-1 particles and exploited this phenomenon to directly examine HIV-1 infectivity of CNS cell types. Using in vitro transcribed mRNAs that were labeled with a fluorescent dye, we showed that these fluorescent mRNAs were packaged into HIV-1 particles by directly examining infected cells using fluorescence microscopy. Cells in culture infected with these labeled HIV-1 particles showed the fluorescent signals of labeled mRNAs by a distinct pattern of punctate, focal signals within the cells which was used to demonstrate that the CXCR4-tropic NL4-3 strain was able to enter microglia and to a lesser extent astrocytes, but not neurons. The strategy used in the present study may represent a novel approach of simplicity, robustness and reliability for versatile applications in HIV studies, such as the determination of infectivity across a broad range of cell types and within subpopulations of an individual cell type by direct visualization of viral entry into cells. PMID:26272129

  14. A multi-level modeling approach examining PTSD symptom reduction during prolonged exposure therapy: moderating effects of number of trauma types experienced, having an HIV-related index trauma, and years since HIV diagnosis among HIV-positive adults.

    Science.gov (United States)

    Junglen, Angela G; Smith, Brian C; Coleman, Jennifer A; Pacella, Maria L; Boarts, Jessica M; Jones, Tracy; Feeny, Norah C; Ciesla, Jeffrey A; Delahanty, Douglas L

    2017-11-01

    People living with HIV (PLWH) have extensive interpersonal trauma histories and higher rates of posttraumatic stress disorder (PTSD) than the general population. Prolonged exposure (PE) therapy is efficacious in reducing PTSD across a variety of trauma samples; however, research has not examined factors that influence how PTSD symptoms change during PE for PLWH. Using multi-level modeling, we examined the potential moderating effect of number of previous trauma types experienced, whether the index trauma was HIV-related or not, and years since HIV diagnosis on PTSD symptom reduction during a 10-session PE protocol in a sample of 51 PLWH. In general, PTSD symptoms decreased linearly throughout the PE sessions. Experiencing more previous types of traumatic events was associated with a slower rate of PTSD symptom change. In addition, LOCF analyses found that participants with a non-HIV-related versus HIV-related index trauma had a slower rate of change for PTSD symptoms over the course of PE. However, analyses of raw data decreased this finding to marginal. Years since HIV diagnosis did not impact PTSD symptom change. These results provide a better understanding of how to tailor PE to individual clients and aid clinicians in approximating the rate of symptom alleviation. Specifically, these findings underscore the importance of accounting for trauma history and index trauma type when implementing a treatment plan for PTSD in PLWH.

  15. Frequency of HIV type 2 infections among blood donor population from India: A 10-year experience

    Directory of Open Access Journals (Sweden)

    Kannangai R

    2010-01-01

    Full Text Available Purpose: In India, HIV-2 epidemic is alongside with HIV-1. Blood banks are introducing nucleic acid testing (NAT for screening. The limitation of NAT systems is the inability to detect HIV-2. Materials and Method : An analysis of HIV screening of a blood bank at a tertiary care center from 1998 to 2007 was carried out. Results : A total of 175026 donors were screened by serological assays and 789 were reactive for HIV antibody. Only 478 (61% were confirmed positive by Western blot/immunoblot. There were 465 (97.2% donations positive for HIV-1, 6 (1.3% for HIV-2 (monotypic infection and 7 (1.5% for HIV-1 and HIV-2 (dual infection. Conclusion : We show the presence of HIV-2 infection among the blood donors and the need for incorporating HIV-2 detection also in the NAT systems.

  16. Investigating signs of recent evolution in the pool of proviral HIV type 1 DNA during years of successful HAART

    DEFF Research Database (Denmark)

    Mens, Helene; Pedersen, Anders G; Jørgensen, Louise B

    2007-01-01

    In order to shed light on the nature of the persistent reservoir of human immunodeficiency virus type 1 (HIV-1), we investigated signs of recent evolution in the pool of proviral DNA in patients on successful HAART. Pro-viral DNA, corresponding to the C2-V3-C3 region of the HIV-1 env gene...... HIV genomes in some patients. Interestingly, stop-codons were present at the same two positions in several independent clones and across patients. Simulation studies indicated that this phenomenon could be explained as the result of parallel evolution and that some sites were inherently more likely...

  17. In vitro replication kinetics of human immunodeficiency virus type 1 (HIV-1) variants in relation to virus load in long-term survivors of HIV-1 infection

    NARCIS (Netherlands)

    Blaak, H.; Brouwer, M.; Ran, L. J.; de Wolf, F.; Schuitemaker, H.

    1998-01-01

    In 7 long-term survivors (LTS) and 8 progressors, all carrying solely non-syncytium-inducing variants, a possible correlation between in vitro virus replicative capacity, virus load, and clinical course of human immunodeficiency virus type 1 (HIV-1) infection was analyzed. Late in infection, 3 LTS

  18. Genital Herpes Simplex Virus Type 2 Shedding Among Adults With and Without HIV Infection in Uganda.

    Science.gov (United States)

    Phipps, Warren; Nakku-Joloba, Edith; Krantz, Elizabeth M; Selke, Stacy; Huang, Meei-Li; Kambugu, Fred; Orem, Jackson; Casper, Corey; Corey, Lawrence; Wald, Anna

    2016-02-01

    Despite the high prevalence of herpes simplex virus type 2 (HSV-2) in sub-Saharan Africa, the natural history of infection among Africans is not well characterized. We evaluated the frequency of genital HSV shedding in HIV-seropositive and HIV-seronegative men and women in Uganda. Ninety-three HSV-2-seropositive Ugandan adults collected anogenital swab specimens for HSV DNA quantification by polymerase chain reaction 3 times daily for 6 weeks. HSV-2 was detected from 2484 of 11 283 swab specimens collected (22%), with a median quantity of 4.3 log10 HSV copies/mL (range, 2.2-8.9 log10 HSV copies/mL). Genital lesions were reported on 749 of 3875 days (19%), and subclinical HSV shedding was detected from 1480 of 9113 swab specimens (16%) collected on days without lesions. Men had higher rates of total HSV shedding (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.3-2.9]; P genital lesions (RR, 2.1 [95% CI, 1.2-3.4]; P = .005), compared with women. No differences in shedding rates or lesion frequency were observed based on HIV serostatus. HSV-2 shedding frequency and quantity are high among HSV-2-seropositive adults in sub-Saharan Africa, including persons with and those without HIV infection. Shedding rates were particularly high among men, which may contribute to the high prevalence of HSV-2 and early acquisition among African women. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. Selective decrease in human immunodeficiency virus type 1 (HIV-1)-induced alpha interferon production by peripheral blood mononuclear cells during HIV-1 infection.

    OpenAIRE

    Ferbas, J; Navratil, J; Logar, A; Rinaldo, C

    1995-01-01

    We previously reported that human immunodeficiency virus type 1 (HIV-1), herpes simplex virus (HSV), and Sendai virus induce higher levels of alpha interferon (IFN-alpha) in blood dendritic cells than in monocytes of healthy donors. In the present study, the levels of IFN-alpha induced by T-cell tropic (IIIb and RF) and monocytotropic (BaL) strains of HIV-1 and by HSV were significantly decreased in peripheral blood mononuclear cells (PBMCs) derived from subjects with asymptomatic and symptom...

  20. The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment.

    Directory of Open Access Journals (Sweden)

    Benjamin B Gelman

    Full Text Available The National NeuroAIDS Tissue Consortium (NNTC performed a brain gene expression array to elucidate pathophysiologies of Human Immunodeficiency Virus type 1 (HIV-1-associated neurocognitive disorders.Twenty-four human subjects in four groups were examined A Uninfected controls; B HIV-1 infected subjects with no substantial neurocognitive impairment (NCI; C Infected with substantial NCI without HIV encephalitis (HIVE; D Infected with substantial NCI and HIVE. RNA from neocortex, white matter, and neostriatum was processed with the Affymetrix® array platform.With HIVE the HIV-1 RNA load in brain tissue was three log(10 units higher than other groups and over 1,900 gene probes were regulated. Interferon response genes (IFRGs, antigen presentation, complement components and CD163 antigen were strongly upregulated. In frontal neocortex downregulated neuronal pathways strongly dominated in HIVE, including GABA receptors, glutamate signaling, synaptic potentiation, axon guidance, clathrin-mediated endocytosis and 14-3-3 protein. Expression was completely different in neuropsychologically impaired subjects without HIVE. They had low brain HIV-1 loads, weak brain immune responses, lacked neuronally expressed changes in neocortex and exhibited upregulation of endothelial cell type transcripts. HIV-1-infected subjects with normal neuropsychological test results had upregulation of neuronal transcripts involved in synaptic transmission of neostriatal circuits.Two patterns of brain gene expression suggest that more than one pathophysiological process occurs in HIV-1-associated neurocognitive impairment. Expression in HIVE suggests that lowering brain HIV-1 replication might improve NCI, whereas NCI without HIVE may not respond in kind; array results suggest that modulation of transvascular signaling is a potentially promising approach. Striking brain regional differences highlighted the likely importance of circuit level disturbances in HIV/AIDS. In

  1. Type and severity of intimate partner violence and its relationship with PTSD in HIV-infected women.

    Science.gov (United States)

    Hansrod, Fatima; Spies, Georgina; Seedat, Soraya

    2015-01-01

    HIV has an impact on the presence and severity of both intimate partner violence (IPV) and posttraumatic stress disorder (PTSD) in infected women. However, the relationship of type and severity of IPV with PTSD in this population has not been adequately explored. We focus on the association between the type and severity of IPV and HIV status and PTSD in a sample of South African women. One hundred and sixty-nine women (114 HIV-positive and 55 HIV-negative controls), matched for geographical area, education, and socio-economic status, were recruited from HIV clinics. Clinical and demographic data were collected, including data on childhood trauma, other traumatic life events, IPV, posttraumatic stress symptoms, problematic alcohol use, and depressive symptoms. HIV-positive women had significantly more depressive symptoms, alcohol abuse, and childhood trauma exposure as well as significantly higher rates of PTSD (25.4%) when compared with uninfected women (10.9%). No significant group differences in the rate, pattern, and severity of physical, sexual, psychological, injury, and negotiation IPV were found. In logistic regression analysis, the rate and severity category of IPV did not significantly predict PTSD in HIV-positive women when childhood trauma and life events were controlled for. Our results indicate the need for screening for alcohol abuse, PTSD and depressive symptoms at HIV wellness, and ARV clinics. The high rates of PTSD in HIV-positive women indicate the need for specialized programs to manage PTSD and minimize negative sequelae in this population. These results also highlight the need for improved screening and prevention of childhood trauma and IPV both in infected and uninfected women.

  2. T cells detect intracellular DNA but fail to induce type I IFN responses: implications for restriction of HIV replication.

    Directory of Open Access Journals (Sweden)

    Randi K Berg

    Full Text Available HIV infects key cell types of the immune system, most notably macrophages and CD4+ T cells. Whereas macrophages represent an important viral reservoir, activated CD4+ T cells are the most permissive cell types supporting high levels of viral replication. In recent years, it has been appreciated that the innate immune system plays an important role in controlling HIV replication, e.g. via interferon (IFN-inducible restriction factors. Moreover, innate immune responses are involved in driving chronic immune activation and the pathogenesis of progressive immunodeficiency. Several pattern recognition receptors detecting HIV have been reported, including Toll-like receptor 7 and Retinoic-inducible gene-I, which detects viral RNA. Here we report that human primary T cells fail to induce strong IFN responses, despite the fact that this cell type does express key molecules involved in DNA signaling pathways. We demonstrate that the DNA sensor IFI16 migrates to sites of foreign DNA localization in the cytoplasm and recruits the signaling molecules stimulator of IFN genes and Tank-binding kinase, but this does not result in expression of IFN and IFN-stimulated genes. Importantly, we show that cytosolic DNA fails to affect HIV replication. However, exogenous treatment of activated T cells with type I IFN has the capacity to induce expression of IFN-stimulated genes and suppress HIV replication. Our data suggest the existence of an impaired DNA signaling machinery in T cells, which may prevent this cell type from activating cell-autonomous anti-HIV responses. This phenomenon could contribute to the high permissiveness of CD4+ T cells for HIV-1.

  3. Recovery of the wild type atomic flexibility in the HIV-1 protease double mutants.

    Science.gov (United States)

    De Conto, Valderes; Braz, Antônio S K; Perahia, David; Scott, Luis P B

    2015-06-01

    The emergence of drug resistant mutations due to the selective pressure exerted by antiretrovirals, including protease inhibitors (PIs), remains a major problem in the treatment of AIDS. During PIs therapy, the occurrence of primary mutations in the wild type HIV-1 protease reduces both the affinity for the inhibitors and the viral replicative capacity compared to the wild type (WT) protein, but additional mutations compensate for this reduced viral fitness. To investigate this phenomenon from the structural point of view, we combined Molecular Dynamics and Normal Mode Analysis to analyze and compare the variations of the flexibility of C-alpha atoms and the differences in hydrogen bond (h-bond) network between the WT and double mutants. In most cases, the flexibility profile of the double mutants was more often similar to that of the WT than to that of the related single base mutants. All single mutants showed a significant alteration in h-bond formation compared to WT. Most of the significant changes occur in the border between the flap and cantilever regions. We found that all the considered double mutants have their h-bond pattern significantly altered in comparison to the respective single base mutants affecting their flexibility profile that becomes more similar to that of WT. This WT flexibility restoration in the double mutants appears as an important factor for the HIV-1 fitness recovery observed in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients.

    Science.gov (United States)

    Goujard, Cécile; Bonarek, Mojgan; Meyer, Laurence; Bonnet, Fabrice; Chaix, Marie-Laure; Deveau, Christiane; Sinet, Martine; Galimand, Julie; Delfraissy, Jean-François; Venet, Alain; Rouzioux, Christine; Morlat, Philippe

    2006-03-01

    Treatment initiation at the time of primary human immunodeficiency virus (HIV) type 1 (HIV-1) infection has become less frequent in recent years. In the French prospective PRIMO Cohort, in which patients are enrolled at the time of primary HIV-1 infection, 30% of the 552 patients recruited during 1996-2004 did not start receiving antiretroviral treatment during the first 3 months after diagnosis. We analyzed the patients' clinical and immunological outcomes and examined potential predictors of disease progression. Progression was defined as the occurrence of an acquired immunodeficiency syndrome (AIDS)-related clinical event or a CD4 cell count <350 cells/mm3. Fifty-six (34%) of the untreated patients experienced immunological progression during a median duration of follow-up of 24 months, and 1 of these patients had an AIDS-related event. The estimated risks of progression were 25%, 34%, and 42% at 1, 2, and 3 years after enrollment, respectively. Compared with patients who did not have progression, those with progression had significantly lower CD4 cell counts at diagnosis (455 vs. 738 cells/mm3), higher plasma HIV RNA levels (4.9 vs. 4.5 log10 copies/mL), and higher HIV DNA levels (3.3 vs. 3.0 log(10) copies/10(6) peripheral blood mononuclear cells [PBMCs]). All 3 parameters were significantly associated with progression in univariate analysis. In multivariate analysis, only the CD4 cell count and HIV DNA level were independently predictive of disease progression (relative hazard for CD4 cell count, 1.84 per decrease of 100 cells/mm3; relative hazard for HIV DNA level, 2.73 per increase of 1 log(10) copies/10(6) PBMCs). Both a low initial CD4 cell count and a high HIV DNA level are predictive of rapid progression of untreated primary HIV-1 infection. Affected patients may therefore benefit from close clinical and laboratory monitoring and/or early administration of treatment.

  5. Molecular phylogenetics of transmitted drug resistance in newly diagnosed HIV Type 1 individuals in Denmark: a nation-wide study

    DEFF Research Database (Denmark)

    Audelin, Anne Margrethe; Gerstoft, Jan; Obel, Niels

    2011-01-01

    without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown......Abstract Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009...... was analyzed for TDR, and molecular-epidemiological links and progression of the infection were described based on data from standardized questionnaires, the prospective Danish HIV Cohort Study, and by phylogenetic analysis. Eighty-five individuals were found to be infected with virus harboring mutations...

  6. Molecular Phylogenetics of Transmitted Drug Resistance in Newly Diagnosed HIV Type 1 Individuals in Denmark, a Nation-Wide Study

    DEFF Research Database (Denmark)

    Audelin, Anne Margrethe; Gerstoft, Jan; Obel, Niels

    2011-01-01

    without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown......Abstract Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009...... was analyzed for TDR, and molecular-epidemiological links and progression of the infection were described based on data from standardized questionnaires, the prospective Danish HIV Cohort Study, and by phylogenetic analysis. Eighty-five individuals were found to be infected with virus harboring mutations...

  7. Association of CCR5-59029 A/G and CCL3L1 copy number polymorphism with HIV type 1 transmission/progression among HIV type 1-seropositive and repeatedly sexually exposed HIV type 1-seronegative North Indians.

    Science.gov (United States)

    Rathore, Anurag; Chatterjee, Animesh; Sivarama, P; Yamamoto, Naohiko; Singhal, Pradeep K; Dhole, Tapan N

    2009-11-01

    The CCR5Delta32 mutation does not account for HIV-1 resistance in the majority of persons who are repeatedly exposed to HIV-1 by high-risk activities but remain seronegative and uninfected. Therefore, we investigated the impact of CCR5 59029 A/G and CCL3L1 copy number polymorphism on HIV-1 disease susceptibility and progression among HIV-1-infected and HIV-1-exposed seronegative North Indians. HIV-1-seropositive (HSP, n = 196) patients, stratified on the basis of disease severity (Stages I, II, and III) and HIV-1-exposed seronegative (HES, n = 47) individuals were genotyped for CCR5-59029 A/G polymorphism by PCR-RFLP and CCL3L1 copy number by the real-time TaqMan PCR method. A group of ethnically matched HIV-1-seronegative (HSN, n = 315) healthy volunteers were also genotyped as controls. Statistical analysis was done by SPSS software. The CCR5-59029 AG genotype was significantly higher in the HES compared with the HSP group (57.44% vs. 37.24%, p = 0.014). The CCL3L1 mean copy number of HES was higher compared with the HSP groups (3.148 +/- 0.291 vs. 2.795 +/- 0.122, p = 0.212), but was not significant when compared with independent samples t test. Possession of CCL3L1 copies 2 was not associated with enhanced or reduced risk of HIV-1 acquisition. Gene-gene interaction studies showed enrichment of the CCR5-59029AG*CCL3L1>2 genotype in the HES group when compared with the HSP group (31.91% vs. 15.81%, p = 0.021, OR = 0.401, CI = 0.194-0.826). The increased frequency of the CCR5-59029AG*CCL3L1>2 genotype among HES individuals led us to conclude that the CCR5-59029 AG genotype and CCL3L1 gene dose appeared to have synergistic or interactive effects and are expected to be involved in the host innate resistance to HIV-1 infection.

  8. High-risk human papillomavirus types in HIV-infected and HIV-uninfected young women in KwaZulu-Natal, South Africa: implications for vaccination.

    Science.gov (United States)

    Mbatha, Joyce N; Taylor, Myra; Kleppa, Elisabeth; Lillebo, Kristine; Galapaththi-Arachchige, Hashini N; Singh, Deepak; Kjetland, Eyrun F; Baay, Marc F D; Mkhize-Kwitshana, Zilungile L

    2017-08-01

    High-risk human papillomavirus (hr-HPV) infections and low-grade squamous intraepithelial lesions occur frequently in young women. The available vaccines cover up to seven hr-HPV genotypes (HPV16, HPV18, HPV31, HPV33, HPV45, HPV52 and HPV58) and two low-risk HPV types (HPV6 and HPV11). The objective of this study was to describe the hr-HPV genotypes present among HIV-uninfected and HIV-infected young women in rural high schools. Cervicovaginal lavages were obtained from sexually active young women recruited from high schools in KwaZulu-Natal (n = 1223). HPV testing was done by the polymerase chain reaction using GP5+/GP6 + primers and enzyme immunoassay. HIV testing was done using rapid test kits. Of the 1223 cervicovaginal lavages, 301 (25%) were positive for hr-HPV. The HPV prevalence was higher in HIV infected (32.20%, 95% CI: 0.27-0.38) than in HIV-uninfected women (22.50%, 95% CI: 0.21-0.26), (p = .001). Similarly, multiple infections were slightly more common in HIV infected (59.32%) than in HIV-uninfected women (53.51%), (p = .37). The nine predominant genotypes in descending order were HPV types 16 (n = 99, 22.10%), 51 (n = 58, 12.91%), 18 (n = 56, 12.50%), 35 (n = 50, 11.10%), 33 (n = 47, 10.82%), 56 (n = 42, 9.31%), 45 (n = 34, 7.60%), 52 (n = 32, 7.14%) and 59 (n = 31, 6.91%). HPV 35, 51, 56 and 59 (40.62%), which are not covered by any vaccine, were among the most prevalent in the schools of KwaZulu-Natal. Four of the most predominant high-risk HPV types in this region are not covered by the new nine-valent HPV vaccine.

  9. Type I Interferon Upregulates Bak and Contributes to T Cell Loss during Human Immunodeficiency Virus (HIV) Infection

    Science.gov (United States)

    Fraietta, Joseph A.; Mueller, Yvonne M.; Yang, Guibin; Boesteanu, Alina C.; Gracias, Donald T.; Do, Duc H.; Hope, Jennifer L.; Kathuria, Noshin; McGettigan, Shannon E.; Lewis, Mark G.; Giavedoni, Luis D.; Jacobson, Jeffrey M.; Katsikis, Peter D.

    2013-01-01

    The role of Type I interferon (IFN) during pathogenic HIV and SIV infections remains unclear, with conflicting observations suggesting protective versus immunopathological effects. We therefore examined the effect of IFNα/β on T cell death and viremia in HIV infection. Ex vivo analysis of eight pro- and anti-apoptotic molecules in chronic HIV-1 infection revealed that pro-apoptotic Bak was increased in CD4+ T cells and correlated directly with sensitivity to CD95/Fas-mediated apoptosis and inversely with CD4+ T cell counts. Apoptosis sensitivity and Bak expression were primarily increased in effector memory T cells. Knockdown of Bak by RNA interference inhibited CD95/Fas-induced death of T cells from HIV-1-infected individuals. In HIV-1-infected patients, IFNα-stimulated gene expression correlated positively with ex vivo T cell Bak levels, CD95/Fas-mediated apoptosis and viremia and negatively with CD4+ T cell counts. In vitro IFNα/β stimulation enhanced Bak expression, CD95/Fas expression and CD95/Fas-mediated apoptosis in healthy donor T cells and induced death of HIV-specific CD8+ T cells from HIV-1-infected patients. HIV-1 in vitro sensitized T cells to CD95/Fas-induced apoptosis and this was Toll-like receptor (TLR)7/9- and Type I IFN-dependent. This sensitization by HIV-1 was due to an indirect effect on T cells, as it occurred in peripheral blood mononuclear cell cultures but not purified CD4+ T cells. Finally, peak IFNα levels and viral loads correlated negatively during acute SIV infection suggesting a potential antiviral effect, but positively during chronic SIV infection indicating that either the virus drives IFNα production or IFNα may facilitate loss of viral control. The above findings indicate stage-specific opposing effects of Type I IFNs during HIV-1 infection and suggest a novel mechanism by which these cytokines contribute to T cell depletion, dysregulation of cellular immunity and disease progression. PMID:24130482

  10. Mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette T [Los Alamos, NM; Fischer, William [Los Alamos, NM; Liao, Hua-Xin [Durham, NC; Haynes, Barton F [Durham, NC; Letvin, Norman [Boston, MA; Hahn,; Beatrice, H [Birmingham, AL

    2011-05-31

    The present invention relates to mosaic clade M HIV-1 Env polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  11. The role of triple infection with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV type-1 on CD4+ lymphocyte levels in the highly HIV infected population of North-Central Nigeria

    Directory of Open Access Journals (Sweden)

    JC Forbi

    2007-06-01

    Full Text Available We set out to determine the seroprevalence of hepatitis B and C among human immunodeficiency virus type-1 (HIV-1 infected individuals in North-Central Nigeria to define the influence of these infections on CD4+ lymphocytes cells among our patients as access to antiretroviral therapy improves across the Nigerian nation. The CD4+ values of 180 confirmed HIV-1 infected individuals were enumerated using a superior fluorescence-activated cell sorter system. These patients were tested for the presence of hepatitis B surface antigen and anti-hepatitis C virus (HCV using third generation enzyme-linked immunosorbent assays. Fifty (27.8% patients had active hepatitis B virus (HBV infection while 33 (18.3% tested positive for anti-HCV antibody. Of these infections, 110 (61.1%, 37 (20.6%, and 20 (11.1% had HIV only, HBV/HIV-only, and HCV/HIV-only respectively. A HBV/HCV/HIV coinfection prevalence of 7.2% (13 patients was recorded. Patients coinfected with HIV/HBV/HCV appeared to have lower CD4+ counts (mean = 107 cells/µl; AIDS defining when compared to HBV/HIV-only (mean = 377 cells/µl, HCV/HIV-only (mean = 373 cells/µl and patients with mono HIV infection (mean = 478 cells/µl. Coinfection with HBV or HCV is relatively common among HIV-infected patients in Nigeria and should be a big consideration in the initiation and choice of therapy.

  12. The role of triple infection with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) type-1 on CD4+ lymphocyte levels in the highly HIV infected population of North-Central Nigeria.

    Science.gov (United States)

    Forbi, J C; Gabadi, S; Alabi, R; Iperepolu, H O; Pam, C R; Entonu, P E; Agwale, S M

    2007-06-01

    We set out to determine the seroprevalence of hepatitis B and C among human immunodeficiency virus type-1 (HIV-1) infected individuals in North-Central Nigeria to define the influence of these infections on CD4+ lymphocytes cells among our patients as access to antiretroviral therapy improves across the Nigerian nation. The CD4+ values of 180 confirmed HIV-1 infected individuals were enumerated using a superior fluorescence-activated cell sorter system. These patients were tested for the presence of hepatitis B surface antigen and anti-hepatitis C virus (HCV) using third generation enzyme-linked immunosorbent assays. Fifty (27.8%) patients had active hepatitis B virus (HBV) infection while 33 (18.3%) tested positive for anti-HCV antibody. Of these infections, 110 (61.1%), 37 (20.6%), and 20 (11.1%) had HIV only, HBV/HIV-only, and HCV/HIV-only respectively. A HBV/HCV/HIV coinfection prevalence of 7.2% (13 patients) was recorded. Patients coinfected with HIV/HBV/HCV appeared to have lower CD4+ counts (mean = 107 cells/microl; AIDS defining) when compared to HBV/HIV-only (mean = 377 cells/microl), HCV/HIV-only (mean = 373 cells/microl) and patients with mono HIV infection (mean = 478 cells/microl). Coinfection with HBV or HCV is relatively common among HIV-infected patients in Nigeria and should be a big consideration in the initiation and choice of therapy.

  13. Effect of Different Types of Exercise in HIV + Mozambican Women Using Antiretroviral Therapy.

    Science.gov (United States)

    Mangona, Lucília; Daca, Timóteo; Tchonga, Francisco; Bule, Odete; Bhatt, Nilesh; Jani, Ilesh; Damasceno, Albertino; Prista, António

    2015-01-01

    The aim of this study was to evaluate and compare the effect of two types of exercises interventions on the regularity and health-related physical fitness in HIV-infected individuals who use antiretroviral therapy (ART). A total of 53 HIV+ African women (mean age=39.5±8.4 years) on ART participated in the study. Subjects were randomly divided into 3 groups, namely, formal exercise (FEG), playful exercise (PEG) and control (CG). During 12 weeks, the exercise groups underwent a program of 1-hour duration with a frequency of 3 times a week. The FEG performed a protocol that included 20 minutes of exercise, cycling at 60 % of V̇O2peak, increasing to 75 % and 85 % in the 4th and 8th weeks, respectively, and a muscular endurance circuit consisted of 6 exercises at 15 repetitions per minute (RM). The PEG followed a program consisting of active games. Before and after the intervention the participants were submitted to a clinical evaluation including immunological parameters (CD4+), cardiovascular risk factors, physical fitness and anthropometry. Comparison of somatic variables before and after the program showed no exercise effect. Immunological and cardiovascular variables were also independent of the exercise group. The main effect was found in cardiorespiratory fitness: exercise groups increased significantly in V̇O2peak (FEG=14.7 %; PEG=11.1 %) with no significant differences in CG. The percentage of high attendance was identical between the two groups. It was concluded that there is no contraindication for exercise in this type of population and the beneficial effect was mainly in cardiorespiratory fitness, regardless of the type of exercise performed.

  14. Low Prevalence of Antiretroviral Resistance Among HIV Type 1-Positive Prisoners in the Southeast United States

    OpenAIRE

    Menezes, Prema; Rosen, David; Wohl, David A.; Kiziah, Nichole; Sebastian, Joseph; Joseph J Eron; White, Becky

    2013-01-01

    Drug-resistant HIV complicates management of HIV infection. Although an estimated 14% of all HIV-positive persons pass through a prison or jail in the United States each year, little is known about the overall prevalence of antiretroviral (ARV) resistance in incarcerated persons. All genotypic sequence data on HIV-positive prisoners in the North Carolina (NC) Department of Corrections (DOC) were obtained from LabCorp. Screening for major resistance mutations in protease (PI) and reverse trans...

  15. Mucosal dendritic cells in HIV-1 susceptibility: a critical role for C-type lectin receptors

    NARCIS (Netherlands)

    Hertoghs, Nina; van Pul, Lisa; Geijtenbeek, Teunis B. H.

    2017-01-01

    Sexual transmission is the major route of HIV-1 infection worldwide. The interaction of HIV-1 with mucosal dendritic cells (DCs) might determine HIV-1 susceptibility as well as initial antiviral immunity controlling virus in the chronic phase. Different DC subsets reside in mucosal tissues and

  16. Human immunodeficiency virus type 1 (HIV-1) and Mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic profiles in a Brazilian cohort.

    Science.gov (United States)

    Pereira, Gisner A S; Stefani, Mariane M A; Araújo Filho, João A; Souza, Luís Carlos S; Stefani, Germana P; Martelli, Celina M T

    2004-11-01

    Co-infections with human immunodeficiency virus (HIV) and Mycobacterium leprae represent unique opportunities to investigate the interaction of both pathogens. We determined the immunologic, virologic, and histopathologic characteristics of 22 co-infected Brazilian patients (median age = 38 years, 81.8% males, 72.2% with paucibacillary leprosy, and 95.4% with acquired immunodeficiency syndrome). The HIV-1 subtypes B and BF predominated in envelope and gag heteroduplex mobility analysis. Borderline tuberculoid (BT), tuberculoid, lepromatous, and indeterminate morphology with CD3+, CD8+, and CD68+ cell distributions compatible with leprosy patients not infected with HIV were observed. Histologic evidence of nerve damage was observed in BT lesions. IgM antibody to M. leprae-specific phenolic glycolipid I was not detected. Two of six co-infected patients monitored during highly active antiretroviral therapy (HAART) developed a leprosy type 1 reaction after an increase in CD4+ cells, suggesting an immune restoration phenomenon. Clinical, immunologic, histopathologic, and virologic features among these HIV-leprosy co-infected patients indicate that each disease progressed as in single infection. However, HAART immune reconstitution may trigger potential adverse effects, such as leprosy acute inflammatory episodes.

  17. Restoration of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Responses in CD8+ T Cells from Late-Stage Patients on Prolonged Antiretroviral Therapy by Stimulation In Vitro with HIV-1 Protein-Loaded Dendritic Cells

    OpenAIRE

    Fan, Zheng; Huang, Xiao-Li; Borowski, LuAnn; John W. Mellors; Rinaldo, Charles R.

    2001-01-01

    We demonstrate that dendritic cells loaded in vitro with human immunodeficiency virus type 1 (HIV-1) protein-liposome complexes activate HLA class I-restricted anti-HIV-1 cytotoxic T-lymphocyte and gamma interferon (IFN-γ) responses in autologous CD8+ T cells from late-stage HIV-1-infected patients on prolonged combination drug therapy. Interleukin-12 enhanced this effect through an interleukin-2- and IFN-γ-mediated pathway. This suggests that dendritic cells from HIV-1-infected persons can b...

  18. Investigating signs of recent evolution in the pool of proviral HIV type 1 DNA during years of successful HAART

    DEFF Research Database (Denmark)

    Mens, Helene; Pedersen, Anders G; Jørgensen, Louise B

    2007-01-01

    In order to shed light on the nature of the persistent reservoir of human immunodeficiency virus type 1 (HIV-1), we investigated signs of recent evolution in the pool of proviral DNA in patients on successful HAART. Pro-viral DNA, corresponding to the C2-V3-C3 region of the HIV-1 env gene......, was collected from PBMCs isolated from 57 patients. Both "consensus" (57 patients) and clonal (7 patients) sequences were obtained from five time points spanning a 24-month period. The main computational strategy was to use maximum likelihood to fit a set of alternative phylogenetic models to the clonal data...

  19. Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Kløverpris, Henrik; Jensen, Kristoffer Jarlov

    2012-01-01

    The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design...... of a universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted...... from conserved regions of HIV-1 that were subdominant (i.e., infrequently targeted) within natural infections. Moreover, the epitopes were predicted to be restricted to at least one of the five common HLA supertypes (HLA-A01, A02, A03, B07, and B44). Here, we validated the resulting peptide...

  20. Anti-HIV-1 Activity of Eight Monofloral Iranian Honey Types

    OpenAIRE

    Mandana Behbahani

    2014-01-01

    Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs) used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR) assay and high pure viral nucleic acid kit. The results demonstrate...

  1. Amphetamine-type stimulants and HIV infection among men who have sex with men: implications on HIV research and prevention from a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Nga Thi Thu Vu

    2015-02-01

    Full Text Available Introduction: HIV infections and the use of amphetamine-type stimulants (ATS among men who have sex with men (MSM have been increasing internationally, but the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to summarize the association between ATS use and HIV infection among MSM. Methods: We conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO for relevant English, peer-reviewed articles of quantitative studies published between 1980 and 25 April 2013. Pooled estimates of the association – prevalence rate ratios (PRR, cross-sectional studies, odds ratio (OR, case-control studies and hazard ratio (HR, longitudinal studies, with 95% Confidence Intervals (CI – were calculated using random-effects models stratified by study design and ATS group (meth/amphetamines vs. ecstasy. We assessed the existence of publication bias in funnel plots and checked for sources of heterogeneity using meta-regression and subgroup analysis. Results: We identified 6710 article titles, screened 1716 abstracts and reviewed 267 full text articles. A total of 35 publications were eligible for data abstraction and meta-analysis, resulting in 56 records of ATS use. Most studies (31/35 were conducted in high-income countries. Published studies used different research designs, samples and measures of ATS use. The pooled association between meth/amphetamine use and HIV infection was statistically significant in all three designs (PRR=1.86; 95% CI: 1.57–2.17; OR=2.73; 95% CI: 2.16–3.46 and HR=3.43; 95% CI: 2.98–3.95, respectively, for cross-sectional, case-control and longitudinal studies. Ecstasy use was not associated with HIV infection in cross-sectional studies (PRR=1.15; 95% CI: 0.88–1.49; OR=3.04; 95% CI: 1.29–7.18 and HR=2.48; 95% CI: 1.42–4.35, respectively, for cross-sectional, case-control and longitudinal studies. Results in cross-sectional studies were highly heterogeneous due to issues with ATS

  2. Prevalence, type, and correlates of trauma exposure among adolescent men and women in Soweto, South Africa: implications for HIV prevention.

    Science.gov (United States)

    Closson, Kalysha; Dietrich, Janan Janine; Nkala, Busi; Musuku, Addy; Cui, Zishan; Chia, Jason; Gray, Glenda; Lachowsky, Nathan J; Hogg, Robert S; Miller, Cari L; Kaida, Angela

    2016-11-25

    Youth trauma exposure is associated with syndemic HIV risk. We measured lifetime prevalence, type, and correlates of trauma experience by gender among adolescents living in the HIV hyper-endemic setting of Soweto, South Africa. Using data from the Botsha Bophelo Adolescent Health Survey (BBAHS), prevalence of "ever" experiencing a traumatic event among adolescents (aged 14-19) was assessed using a modified Traumatic Event Screening Inventory-Child (TESI-C) scale (19 items, study alpha = 0.63). We assessed self-reported number of potentially traumatic events (PTEs) experienced overall and by gender. Gender-stratified multivariable logistic regression models assessed independent correlates of 'high PTE score' (≥7 PTEs). Overall, 767/830 (92%) participants were included (58% adolescent women). Nearly all (99.7%) reported experiencing at least one PTE. Median PTE was 7 [Q1,Q3: 5-9], with no gender differences (p = 0.19). Adolescent men reported more violent PTEs (e.g., "seen an act of violence in the community") whereas women reported more non-violent HIV/AIDS-related PTEs (e.g., "family member or someone close died of HIV/AIDS"). High PTE score was independently associated with high food insecurity among adolescent men and women (aOR = 2.63, 95%CI = 1.36-5.09; aOR = 2.57, 95%CI = 1.55-4.26, respectively). For men, high PTE score was also associated with older age (aOR = 1.40/year, 95%CI = 1.21-1.63); and recently moving to Soweto (aOR = 2.78, 95%CI = 1.14-6.76). Among women, high PTE score was associated with depression using the CES-D scale (aOR = 2.00, 95%CI = 1.31-3.03,) and inconsistent condom use vs. no sexual experience (aOR = 2.69, 95%CI = 1.66-4.37). Nearly all adolescents in this study experienced trauma, with gendered differences in PTE types and correlates, but not prevalence. Exposure to PTEs were distributed along social and gendered axes. Among adolescent women, associations with depression and inconsistent condom use suggest pathways for HIV risk. HIV

  3. Prevalence, type, and correlates of trauma exposure among adolescent men and women in Soweto, South Africa: implications for HIV prevention

    Directory of Open Access Journals (Sweden)

    Kalysha Closson

    2016-11-01

    Full Text Available Abstract Background Youth trauma exposure is associated with syndemic HIV risk. We measured lifetime prevalence, type, and correlates of trauma experience by gender among adolescents living in the HIV hyper-endemic setting of Soweto, South Africa. Methods Using data from the Botsha Bophelo Adolescent Health Survey (BBAHS, prevalence of “ever” experiencing a traumatic event among adolescents (aged 14–19 was assessed using a modified Traumatic Event Screening Inventory-Child (TESI-C scale (19 items, study alpha = 0.63. We assessed self-reported number of potentially traumatic events (PTEs experienced overall and by gender. Gender-stratified multivariable logistic regression models assessed independent correlates of ‘high PTE score’ (≥7 PTEs. Results Overall, 767/830 (92% participants were included (58% adolescent women. Nearly all (99.7% reported experiencing at least one PTE. Median PTE was 7 [Q1,Q3: 5-9], with no gender differences (p = 0.19. Adolescent men reported more violent PTEs (e.g., “seen an act of violence in the community” whereas women reported more non-violent HIV/AIDS-related PTEs (e.g., “family member or someone close died of HIV/AIDS”. High PTE score was independently associated with high food insecurity among adolescent men and women (aOR = 2.63, 95%CI = 1.36-5.09; aOR = 2.57, 95%CI = 1.55-4.26, respectively. For men, high PTE score was also associated with older age (aOR = 1.40/year, 95%CI = 1.21-1.63; and recently moving to Soweto (aOR = 2.78, 95%CI = 1.14-6.76. Among women, high PTE score was associated with depression using the CES-D scale (aOR = 2.00, 95%CI = 1.31-3.03, and inconsistent condom use vs. no sexual experience (aOR = 2.69, 95%CI = 1.66-4.37. Conclusion Nearly all adolescents in this study experienced trauma, with gendered differences in PTE types and correlates, but not prevalence. Exposure to PTEs were distributed along social and gendered axes. Among adolescent women, associations with

  4. Cell type specificity and structural determinants of IRES activity from the 5' leaders of different HIV-1 transcripts.

    Science.gov (United States)

    Plank, Terra-Dawn M; Whitehurst, James T; Kieft, Jeffrey S

    2013-07-01

    Internal ribosome entry site (IRES) RNAs are important regulators of gene expression, but their diverse molecular mechanisms remain partially understood. The HIV-1 gag transcript leader contains an IRES that may be a good model for understanding the function of many other IRESs. We investigated the possibility that this IRES' function is linked to both the structure of the RNA and its cellular environment. We find that in the context of a bicistronic reporter construct, HIV-1 gag IRES' activity is cell type-specific, with higher activity in T-cell culture systems that model the natural target cells for HIV-1 infection. This finding underscores how an IRES may be fine tuned to function in certain cells, perhaps owing to cell type-specific protein factors. Using RNA probing and mutagenesis, we demonstrate that the HIV-1 gag IRES does not use pre-folded RNA structure to drive function, a finding that gives insight into how conformationally dynamic IRESs operate. Furthermore, we find that a common exon drives IRES activity in a diverse set of alternatively spliced transcripts. We propose a mechanism in which a structurally plastic RNA element confers the ability to initiate translation internally, and activity from this common element is modulated by 3' nucleotides added by alternative splicing.

  5. Multi-nucleoside reverse transcriptase inhibitor resistant HIV type-1 in a patient from Sierra Leone failing stavudine, lamivudine and nevirapine

    NARCIS (Netherlands)

    Hamers, Raph L.; Wensing, Annemarie M. J.; Back, Nicole K. T.; Arcilla, Maria S.; Frissen, Jos P. H.

    2011-01-01

    We report a 33-year-old HIV type-1 (HIV-1)-infected male from Sierra Leone who harboured extensive drug resistance mutations to all nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs, including the multi-NRTI-resistance Q151M complex, K65R, M184I and Y181I, after using standard

  6. Immune restoration and onset of new AIDS-defining events with combination antiretroviral therapy in HIV type-1-infected immigrants in the Netherlands

    NARCIS (Netherlands)

    Kesselring, Anouk M.; Gras, Luuk; Wit, Ferdinand W.; Smit, Colette; Geerlings, Suzanne E.; Mulder, Jan W.; Schreij, Gerrit; Sprenger, Herman G.; Reiss, Peter; de Wolf, Frank

    2010-01-01

    Background: We investigated differences in immune restoration and onset of new AIDS-defining events on combination antiretroviral therapy (cART) among HIV type-1 (HIV-1)-infected patients of different regional origin now living in the Netherlands. Methods: Treatment-naive adults reaching plasma

  7. Antiretroviral therapy-induced Leber’s hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Anand Moodley

    2014-05-01

    Full Text Available Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON, a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects. 

  8. Epidemiological networks and drug resistance of HIV type 1 in Krasnoyarsk region, Russia

    NARCIS (Netherlands)

    Rumyantseva, Olga A.; Olkhovskiy, Igor A.; Malysheva, Marina A.; Ruzaeva, Ludmila A.; Vasiliev, Alexander V.; Kazennova, Elena V.; Bobkova, Marina R.; Lukashov, Vladimir V.

    2009-01-01

    To study the molecular epidemiology of HIV-1 in Krasnoyarsk region, Russia, where HIV-1 has spread rapidly since 2000, we obtained pol sequences from individuals living in this region (n = 67) as well as in the geographically closely related Altay region (n = 13). In both regions, subtype A viruses

  9. Impact of HIV Type 1 DNA Levels on Spontaneous Disease Progression: A Meta-Analysis

    DEFF Research Database (Denmark)

    Tsiara, Chrissa G; Nikolopoulos, Georgios K; Bagos, Pantelis G

    2012-01-01

    , and to compare the prognostic information obtained by HIV-1 DNA with that derived from plasma HIV-1 RNA. Eligible articles were identified through a comprehensive search of Medline, ISI Web of Science, Scopus, and Google Scholar. The analysis included univariate and bivariate random-effects models...

  10. Response to “Rapid tests for HIV type discrimination in West Africa may perform differently”

    National Research Council Canada - National Science Library

    Tchounga, Boris K; Ekouevi, Didier K; Eholie, Serge P

    2015-01-01

    ... of each test used for the initial discrimination of HIV‐positive patients. Our team previously conducted in 2004 a field evaluation of rapid HIV serologic tests in Côte d'Ivoire and highlighted the lower accuracy of Genie II for differentiating between HIV‐1, HIV‐2 and dually reactive patients [ 4 ]. In our most recent study, the initial HIV diag...

  11. Longing for belonging: Adolescents' experiences of living with HIV in different types of families in Swaziland

    NARCIS (Netherlands)

    Shabalala, F.S.

    2017-01-01

    This study illuminates adolescents’ everyday life experiences of living with HIV in different family contexts in the Manzini region in Swaziland, and the tactics they used to navigate the social and health system environments in their management of the HIV illness and disease. A significant

  12. Nucleic acids encoding mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    Science.gov (United States)

    Korber, Bette T; Fischer, William; Liao, Hua-Xin; Haynes, Barton F; Letvin, Norman; Hahn, Beatrice H

    2015-04-21

    The present invention relates to nucleic acids encoding mosaic clade M HIV-1 Env polypeptides and to compositions and vectors comprising same. The nucleic acids of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  13. Quantitation of Human Immunodeficiency Virus Type 1 (HIV-1) RNA in Cell-Free Cervicovaginal Secretions: Comparison of Reverse Transcription-PCR Amplification (AMPLICOR HIV-1 MONITOR 1.5) with Enhanced-Sensitivity Branched-DNA Assay (Quantiplex 3.0)

    Science.gov (United States)

    Si-Mohamed, Ali; Andreoletti, Laurent; Colombet, Isabelle; Carreno, Marie-Paule; Lopez, Gladys; Chatelier, Gilles; Kazatchkine, Michel D.; Belec, Laurent

    2001-01-01

    Two commercially available hypersensitive assays for human immunodeficiency virus type 1 (HIV-1) RNA quantitation, AMPLICOR HIV-1 Monitor Test 1.5 and Quantiplex HIV RNA 3.0, were compared to detect and quantify HIV-1 RNA in the cell-free fraction of cervicovaginal secretions collected by vaginal washing. Three panel specimens were used: pooled cervicovaginal secretions spiked with HIV-1 subtype A or HIV-1 subtype B and cervicovaginal lavages from HIV-positive and HIV-negative women. Compared to the AMPLICOR HIV-1 Monitor Test 1.5 assay, the Quantiplex HIV-1 3.0 assay yielded higher estimates of HIV-1 RNA concentrations in several tested samples spiked with HIV-1 RNA subtype A, as well as subtype B, particularly samples containing low amounts of HIV-1 RNA. The sensitivity and specificity of the AMPLICOR HIV-1 Monitor Test 1.5 assay were 93 and 100%, respectively; the sensitivity and specificity of the Quantiplex HIV RNA 3.0 assay were 97 and 50%, respectively. In conclusion, in quantifying HIV-1 RNA in cervicovaginal secretions, the Quantiplex HIV RNA 3.0 may lack specificity, and the AMPLICOR HIV-1 Monitor Test 1.5 assay, although highly specific, may lack sensitivity. PMID:11376034

  14. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

    2009-04-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  15. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Directory of Open Access Journals (Sweden)

    Gretja Schnell

    2009-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 invades the central nervous system (CNS shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA, targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2 mean = 2.27 days. However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2 range = 9.85 days to no initial decay. The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  16. Short communication: HIV type 1 escapes inactivation by saliva via rapid escape into oral epithelial cells.

    Science.gov (United States)

    Dietrich, Elizabeth A; Gebhard, Kristin H; Fasching, Claudine E; Giacaman, Rodrigo A; Kappes, John C; Ross, Karen F; Herzberg, Mark C

    2012-12-01

    Saliva contains anti-HIV-1 factors, which show unclear efficacy in thwarting mucosal infection. When incubated in fresh, unfractionated whole saliva, infectious HIV-1 IIIb and BaL (X4- and R5-tropic, respectively) persisted from 4 to at least 30 min in a saliva concentration-dependent manner. In salivary supernatant for up to 6 h, both infectious HIV-1 strains "escaped" into immortalized oral epithelial cells; infectious BaL showed selectively enhanced escape in the presence of saliva. Fluorescently labeled HIV-1 virus-like particles entered oral epithelial cells within minutes of exposure. Using a previously unrecognized mechanism, therefore, strains of HIV-1 escape inactivation by saliva via rapid uptake into oral epithelial cells.

  17. Inhibition of human immunodeficiency virus type 1 (HIV-1) penetration into target cells by synthetic peptides mimicking the N-terminus of the HIV-1 transmembrane glycoprotein

    NARCIS (Netherlands)

    Slepushkin, V. A.; Kornilaeva, G. V.; Andreev, S. M.; Sidorova, M. V.; Petrukhina, A. O.; Matsevich, G. R.; Raduk, S. V.; Grigoriev, V. B.; Makarova, T. V.; Lukashov, V. V.

    1993-01-01

    To investigate the mechanism of action of the 22-amino-acid HIV fusion peptide on HIV infection, we studied its influence on virus adsorption and HIV-induced syncytium formation. The effect of the peptide preparations on the synthesis of viral antigens in HIV-infected cell cultures was determined by

  18. Types and Characteristics of Childhood Sexual Abuse: How Do They Matter in HIV Sexual Risk Behaviors Among Women in Methadone Treatment in New York City?

    Science.gov (United States)

    Engstrom, Malitta; Winham, Katherine; Gilbert, Louisa

    2016-01-01

    Childhood sexual abuse (CSA) is often considered an important distal factor in HIV sexual risk behaviors; however, there are limited and mixed findings regarding this relationship among women experiencing substance use problems. In addition, research with this population of women has yet to examine differences in observed CSA-HIV sexual risk behaviors relationships by CSA type and characteristics. This study examines relationships between CSA coding, type, and characteristics and HIV sexual risk behaviors with main intimate partners among a random sample of 390 women in methadone treatment in New York City who completed individual interviews with trained female interviewers. Findings from logistic regression analyses indicate that CSA predicts substance use with sexual activity, with variations by CSA coding, type, and characteristics; however, the role of CSA is more limited than expected. Having a main partner with HIV risk mediates some relationships between CSA and drinking four or more drinks prior to sex. Intimate partner violence is the most consistent predictor of sexual risk behaviors. Other salient factors include polysubstance use, depression, social support, recent incarceration, relationship characteristics, and HIV status. This study contributes to understanding of relationships between CSA and HIV sexual risk behaviors and key correlates associated with HIV sexual risk behaviors among women in methadone treatment. It also highlights the complexity of measuring CSA and its association with sexual risk behaviors and the importance of comprehensive approaches to HIV prevention that address psychological, relational, situational, and substance use experiences associated with sexual risk behaviors among this population.

  19. Type I interferons and interferon regulatory factors regulate TNF-related apoptosis-inducing ligand (TRAIL in HIV-1-infected macrophages.

    Directory of Open Access Journals (Sweden)

    Yunlong Huang

    Full Text Available TNF-related apoptosis-inducing ligand (TRAIL is a member of the TNF family that participates in HIV-1 pathogenesis through the depletion of CD4+ T cells. TRAIL is expressed on the cell membrane of peripheral immune cells and can be cleaved into a soluble, secreted form. The regulation of TRAIL in macrophages during HIV-1 infection is not completely understood. In this study, we investigated the mechanism(s of TRAIL expression in HIV-1-infected macrophages, an important cell type in HIV-1 pathogenesis. A human monocyte-derived macrophage (MDM culture system was infected with macrophage-tropic HIV-1(ADA, HIV-1(JR-FL, or HIV-1(BAL strains. TRAIL, predominantly the membrane-bound form, increased following HIV-1 infection. We found that HIV-1 infection also induced interferon regulatory factor (IRF-1, IRF-7 gene expression and signal transducers and activators of transcription 1 (STAT1 activation. Small interfering RNA knockdown of IRF-1 or IRF-7, but not IRF-3, reduced STAT1 activation and TRAIL expression. Furthermore, the upregulation of IRF-1, IRF-7, TRAIL, and the activation of STAT1 by HIV-1 infection was reduced by the treatment of type I interferon (IFN-neutralizing antibodies. In addition, inhibition of STAT1 by fludarabine abolished IRF-1, IRF-7, and TRAIL upregulation. We conclude that IRF-1, IRF-7, type I IFNs, and STAT1 form a signaling feedback loop that is critical in regulating TRAIL expression in HIV-1-infected macrophages.

  20. HIV risks vary according to type of sex work in a cross-sectional survey from Nagaland, India.

    Science.gov (United States)

    O'Halloran, Anna B Z; Armstrong, Gregory; Medhi, Gajendra K; Sono, Collins Z; Mahanta, Jagadish; Kermode, Michelle

    2014-11-12

    Human immunodeficiency virus (HIV) infection is a significant problem among female sex workers (FSWs) in Nagaland, India. Place of solicitation and sex vary considerably in this context. The aim of this study was to investigate the relationship between categories of sex work and HIV risks. In 2009 a survey was undertaken among 417 FSWs in Dimapur, Nagaland using an interviewer-administered questionnaire and blood and urine samples. Using this data, we constructed a typology of sex work by combining usual place of solicitation and place of sex, and examined variations in demographics, sex work patterns, sexually transmitted infections (STIs) and HIV prevalence across typology categories. Binary logistic regression analyses were done to examine the association between category of sex work and HIV, STIs, and condom use. By combining place of solicitation with place of sex, seven distinct categories of sex work emerged. The largest category were women who usually solicited in a public place and had sex in a rented room or lodge (31.7%, n = 132). One-tenth of participants were HIV positive (10.3%) and 35.4% had at least one STI (reactive syphilis serology, gonorrhoea or chlamydia). FSWs who both solicited and entertained in a rented room or lodge (OR = 13.3; 95% CI 2.2, 81.5) and those who solicited by phone and had sex in a rented room or lodge (OR = 6.3; 95% CI 1.0, 38.0) were more likely to be HIV positive compared to home-based FSWs. Women who both solicited and entertained in public (OR = 6.7; 95% CI 1.6, 28.0) and who solicited in public and entertained in a rented room or lodge (OR = 2.5; 95% CI 1.1, 6.0) were more likely to test positive for an STI compared to home-based FSWs. The results indicate that different categories of sex work are associated with different HIV and STI risk profiles. Local contextual understanding of the different types of sex work and the associated levels of risk assist NGOs to target their interventions more

  1. Documentation of subtype C HIV Type 1 strains in Argentina, Paraguay, and Uruguay.

    Science.gov (United States)

    Carrion, G; Eyzaguirre, L; Montano, S M; Laguna-Torres, V; Serra, M; Aguayo, N; Avila, M M; Ruchansky, D; Pando, M A; Vinoles, Jose; Perez, J; Barboza, A; Chauca, G; Romero, A; Galeano, A; Blair, P J; Weissenbacher, M; Birx, D L; Sanchez, J L; Olson, J G; Carr, J K

    2004-09-01

    HIV subtypes B, F, and BF recombinants have been previously reported in South America. This report describes the presence of HIV-1 subtype C infection in the countries of Argentina, Uruguay, and Paraguay dating back to at least 1999. Surveillance for uncommon non-B/non-F subtype viruses circulating in South America has been conducted in samples obtained from nine countries. Peripheral blood mononuclear cells (PBMC), dried filter paper (FP), and fresh blood (FB) samples were collected from HIV-positive patients from Ecuador, Colombia, Venezuela, Peru, Chile, Bolivia, Argentina, Uruguay, and Paraguay. From a total of 2962 HIV seropositive samples examined during a 9-year period (1995-2003), only 11 (0.4%) were found to be infected with non-B/non-F HIV variants. Eight of these 11 strains were determined to be subtype C by heteroduplex mobility assay (HMA). Five of these 8 strains were further characterized by sequencing and phylogenetic analysis of the protease (Pro) and reverse transcriptase (RT) region of the genome and two were sequenced full length. One of the strains was found to be a unique BC recombinant. The spread of a third subtype of HIV, subtype C, should raise the question of its potential future role in the HIV epidemic in this region.

  2. HIV type 1 Thai subtype E is predominant in South Vietnam.

    Science.gov (United States)

    Menu, E; Truong, T X; Lafon, M E; Nguyen, T H; Müller-Trutwin, M C; Nguyen, T T; Deslandres, A; Chaouat, G; Duong, Q T; Ha, B K; Fleury, H J; Barré-Sinoussi, F

    1996-05-01

    Samples of peripheral blood mononuclear cells from 50 HIV-1-infected individuals in South Vietnam were analyzed to determine with which HIV-1 subtype the subjects were infected. Participants were from Ho Chi Minh city and five surrounding provinces; 16 samples from female prostitutes, 32 from IV drug users, and one each from a man and woman not in any HIV risk group. 32 individuals were therefore most likely infected by IV drug use and the rest through sexual contacts. PCR amplification and heteroduplex mobility assay found all but one case to be infected with HIV-1 subtype E. The only nonsubtype E infection was HIV-1 subtype B in a woman sexually infected by her seropositive partner who was most likely exposed to the virus in Europe. HIV-1 subtype E strongly predominates in South Vietnam. The homogeneous geographic distribution of subtype E suggests the recent introduction of the virus into the country. A Thai origin can be considered given the genetic relationship between the Thai and Vietnamese subtypes E. It may be assumed that subtype E infections of Vietnamese prostitutes are related to the progressive entry and spread of HIV-1 subtype E from Thailand to Cambodia and then to southern Vietnam.

  3. Interleukin-27 is a potent inhibitor of cis HIV-1 replication in monocyte-derived dendritic cells via a type I interferon-independent pathway.

    Directory of Open Access Journals (Sweden)

    Qian Chen

    Full Text Available IL-27, a member of the IL-12 family of cytokines, plays an important and diverse role in the function of the immune system. Whilst generally recognized as an anti-inflammatory cytokine, in addition IL-27 has been found to have broad anti-viral effects. Recently, IL-27 has been shown to be a potent inhibitor of HIV-1 infection in CD4+ T cells and macrophages. The main objective of this study was to see whether IL-27 has a similar inhibitory effect on HIV-1 replication in dendritic cells (DCs. Monocytes were differentiated into immature DCs (iDCs and mature DCs (mDCs with standard techniques using a combination of GM-CSF, IL-4 and LPS. Following differentiation, iDCs were infected with HIV-1 and co-cultured in the presence or absence of IL-27. IL-27 treated DCs were shown to be highly potent inhibitors of cis HIV-1, particularly of CCR5 tropic strains. Of note, other IL-12 family members (IL-12, IL-23 and IL-35 had no effect on HIV-1 replication. Microarray studies of IL-27 treated DCs showed no up-regulation of Type I (IFN gene expression. Neutralization of the Type-I IFN receptor had no impact on the HIV inhibition. Lastly, IL-27 mediated inhibition was shown to act post-viral entry and prior to completion of reverse transcription. These results show for the first time that IL-27 is a potent inhibitor of cis HIV-1 infection in DCs by a Type I IFN independent mechanism. IL-27 has previously been reported to inhibit HIV-1 replication in CD4+ T cells and macrophages, thus taken together, this cytokine is a potent anti-HIV agent against all major cell types targeted by the HIV-1 virus and may have a therapeutic role in the future.

  4. Risk factors for herpes simplex virus type 2 and HIV among women at high risk in northwestern Tanzania: preparing for an HSV-2 intervention trial

    National Research Council Canada - National Science Library

    Watson-Jones, Deborah; Weiss, Helen A; Rusizoka, Mary; Baisley, Kathy; Mugeye, Kokugonza; Changalucha, John; Everett, Dean; Balira, Rebecca; Knight, Louise; Ross, David; Hayes, Richard J

    2007-01-01

    To determine prevalence of and risk factors for herpes simplex virus type 2 (HSV-2) and HIV among women being screened for a randomized, controlled trial of HSV suppressive therapy in northwestern Tanzania...

  5. High prevalence of herpes simplex virus (HSV)- type 2 co-infection among HIV-positive women in Ukraine, but no increased HIV mother-to-child transmission risk.

    Science.gov (United States)

    Aebi-Popp, Karoline; Bailey, Heather; Malyuta, Ruslan; Volokha, Alla; Thorne, Claire

    2016-04-27

    Over 3500 HIV-positive women give birth annually in Ukraine, a setting with high prevalence of sexually transmitted infections. Herpes simplex virus Type 2 (HSV-2) co-infection may increase HIV mother-to-child transmission (MTCT) risk. We explored factors associated with HSV-2 seropositivity among HIV-positive women in Ukraine, and its impact on HIV MTCT. Data on 1513 HIV-positive women enrolled in the Ukraine European Collaborative Study from 2007 to 2012 were analysed. Poisson and logistic regression models respectively were fit to investigate factors associated with HSV-2 seropositivity and HIV MTCT. Median maternal age was 27 years (IQR 24-31), 53% (796/1513) had been diagnosed with HIV during their most recent pregnancy and 20% had a history of injecting drugs. Median antenatal CD4 count was 430 cells/mm(3) (IQR 290-580). Ninety-six percent had received antiretroviral therapy antenatally. HSV-2 seroprevalence was 68% (1026/1513). In adjusted analyses, factors associated with HSV-2 antibodies were history of pregnancy termination (APR 1.30 (95% CI 1.18-1.43) for ≥ 2 vs. 0), having an HIV-positive partner (APR 1.15 (95% CI 1.05-1.26) vs partner's HIV status unknown) and HCV seropositivity (APR 1.23 (95 % CI 1.13-1.35)). The overall HIV MTCT rate was 2.80% (95% CI 1.98-3.84); no increased HIV MTCT risk was detected among HSV-2 seropositive women after adjusting for known risk factors (AOR 1.43 (95% CI 0.54-3.77). No increased risk of HIV MTCT was detected among the 68% of HIV-positive women with antibodies to HSV-2, in this population with an overall HIV MTCT rate of 2.8%. Markers of ongoing sexual risk among HIV-positive HSV-2 seronegative women indicate the importance of interventions to prevent primary HSV-2 infection during pregnancy in this high-risk group.

  6. Incorporating the type and direction information in predicting novel regulatory interactions between HIV-1 and human proteins using a biclustering approach

    Science.gov (United States)

    2014-01-01

    Background Discovering novel interactions between HIV-1 and human proteins would greatly contribute to different areas of HIV research. Identification of such interactions leads to a greater insight into drug target prediction. Some recent studies have been conducted for computational prediction of new interactions based on the experimentally validated information stored in a HIV-1-human protein-protein interaction database. However, these techniques do not predict any regulatory mechanism between HIV-1 and human proteins by considering interaction types and direction of regulation of interactions. Results Here we present an association rule mining technique based on biclustering for discovering a set of rules among human and HIV-1 proteins using the publicly available HIV-1-human PPI database. These rules are subsequently utilized to predict some novel interactions among HIV-1 and human proteins. For prediction purpose both the interaction types and direction of regulation of interactions, (i.e., virus-to-host or host-to-virus) are considered here to provide important additional information about the regulation pattern of interactions. We have also studied the biclusters and analyzed the significant GO terms and KEGG pathways in which the human proteins of the biclusters participate. Moreover the predicted rules have also been analyzed to discover regulatory relationship between some human proteins in course of HIV-1 infection. Some experimental evidences of our predicted interactions have been found by searching the recent literatures in PUBMED. We have also highlighted some human proteins that are likely to act against the HIV-1 attack. Conclusions We pose the problem of identifying new regulatory interactions between HIV-1 and human proteins based on the existing PPI database as an association rule mining problem based on biclustering algorithm. We discover some novel regulatory interactions between HIV-1 and human proteins. Significant number of predicted

  7. MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1 seropositive individuals

    Directory of Open Access Journals (Sweden)

    Smith Stephen M

    2008-12-01

    Full Text Available Abstract MicroRNAs (miRNAs play diverse roles in regulating cellular and developmental functions. We have profiled the miRNA expression in peripheral blood mononuclear cells from 36 HIV-1 seropositive individuals and 12 normal controls. The HIV-1-positive individuals were categorized operationally into four classes based on their CD4+ T-cell counts and their viral loads. We report that specific miRNA signatures can be observed for each of the four classes.

  8. Detection of human immunodeficiency virus type 1 (HIV-1) Tat protein by aptamer-based biosensors

    Science.gov (United States)

    Hashim, Uda; Fatin, M. F.; Ruslinda, A. R.; Gopinath, Subash C. B.; Uda, M. N. A.

    2017-03-01

    A study was conducted to detect the human immunodeficiency virus (HIV-1) Tat protein using interdigitated electrodes. The measurements and images of the IDEs' finger gaps and the images of chitosan-carbon nanotubes deposited on top of the interdigitated electrodes were taken using the Scanning Electron Microscope. The detection of HIV-1 Tat protein was done using split aptamers and aptamer tail. Biosensors were chosen as diagnostic equipment due to their rapid diagnostic capabilities.

  9. Niacin nutritional status in HIV type 1-positive children: preliminary data.

    Science.gov (United States)

    Tremeschin, Marina Hjertquist; Cervi, Maria Célia; Camelo Júnior, José Simon; Negrini, Bento Vidal de Moura; Martinez, Francisco Eulógio; Motta, Fabrízio; Meirelles, Mônica Silva de Souza; Vanucchhi, Helio; Monteiro, Jacqueline Pontes

    2007-05-01

    HIV infection induces a state of pellagra in cell culture models. This study compared the nutritional status and the 24-hour urine excretion of N-methylnicotinamide between HIV-positive children and HIV-negative children who were or were not born of mothers with HIV-1 infection. Forty patients were included in the study: HIV-positive children (group 1; n = 20), HIV-negative children born to infected mothers (group 2; n = 10), and HIV-negative control children (group 3; n = 10). Usual dietary intake was assessed by a semiquantitative food-frequency questionnaire. Weight and height were assessed and compared with the reference data of the U.S. National Center for Health Statistics/Centers for Disease Control and Prevention. For the estimation of fat-free mass and total body water, bioelectrical impedance technique was used. N-methylnicotinamide was measured by a modified method of high-performance liquid chromatography. Groups were matched in relation to age, sex, percentage of malnutrition, anthropometric measures, and body composition. Daily niacin intake did not differ statistically across groups (group 1 = 18.0 +/- 11.4 mg/day; group 2 = 18.9 +/- 8.0 mg/day; group 3 = 14.2 +/- 5.2 mg/day), nor did intake of tryptophan, vitamin B6, and zinc. The values of urinary niacin per gram of creatinine were similar and adequate across the groups (group 1 = 4.68 [0.75-14.9]; group 2 = 3.74 [1.13-5.69]; group 3 = 3.85 [1.80-8.19]). HIV-positive children excreted the same amount of N-methylnicotinamide in urine as did the control children. These findings may be attributed to similarities in nutritional status, adequate intestinal absorption (no children experienced diarrhea) and stable clinical condition.

  10. Nucleic acids encoding modified human immunodeficiency virus type 1 (HIV-1) group M consensus envelope glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Haynes, Barton F [Durham, NC; Gao, Feng [Durham, NC; Korber, Bette T [Los Alamos, NM; Hahn, Beatrice H [Birmingham, AL; Shaw, George M [Birmingham, AL; Kothe, Denise [Birmingham, AL; Li, Ying Ying [Hoover, AL; Decker, Julie [Alabaster, AL; Liao, Hua-Xin [Chapel Hill, NC

    2011-12-06

    The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralizes a wide spectrum of HIV primary isolates and/or to an immunogen that induces a T cell immune response. The invention also relates to a method of inducing anti-HIV antibodies, and/or to a method of inducing a T cell immune response, using such an immunogen. The invention further relates to nucleic acid sequences encoding the present immunogens.

  11. Inhibition of human immunodeficiency virus type-1 (HIV-1 glycoprotein-mediated cell-cell fusion by immunor (IM28

    Directory of Open Access Journals (Sweden)

    Akoume Marie-Yvonne

    2005-02-01

    Full Text Available Abstract Background Immunor (IM28, an analog of dehydroepiandrosterone (DHEA, inhibits human immunodeficiency virus type-1 (HIV-1 by inhibiting reverse transcriptase. We assessed the ability of IM28 to inhibit the cell-cell fusion mediated by HIV envelope glycoprotein in an in vitro system. For this purpose, we co-cultured TF228.1.16, a T-cell line expressing stably HIV-1 glycoprotein envelopes, with an equal number of 293/CD4+, another T cell line expressing CD4, and with the SupT1 cell line with or without IM28. Results In the absence of IM28, TF228.1.16 fused with 293/CD4+, inducing numerous large syncytia. Syncytia appeared more rapidly when TF228.1.16 was co-cultured with SupT1 cells than when it was co-cultured with the 293/CD4+ cell line. IM28 (1.6 – 45 μg/ml completely inhibits cell-cell fusion. IM28 also prevented the development of new syncytia in infected cells and protected naive SupT1 cells from HIV-1 infection. Evaluation of 50% inhibitory dose (IC50 of IM28 revealed a decrease in HIV-1 replication with an IC50 of 22 mM and 50% cytotoxicity dose (CC50 as determined on MT2 cells was 75 mM giving a selectivity index of 3.4 Conclusions These findings suggest that IM28 exerts an inhibitory action on the env proteins that mediate cell-cell fusion between infected and healthy cells. They also suggest that IM28 interferes with biochemical processes to stop the progression of existing syncytia. This property may lead to the development of a new class of therapeutic drug.

  12. Two types of nanoparticle-based bio-barcode amplification assays to detect HIV-1 p24 antigen

    Directory of Open Access Journals (Sweden)

    Dong Huahuang

    2012-08-01

    Full Text Available Abstract Background HIV-1 p24 antigen is a major viral component of human immunodeficiency virus type 1 (HIV-1 which can be used to identify persons in the early stage of infection and transmission of HIV-1 from infected mothers to infants. The detection of p24 is usually accomplished by using an enzyme-linked immunosorbent assay (ELISA with low detection sensitivity. Here we report the use of two bio-barcode amplification (BCA assays combined with polymerase chain reaction (PCR and gel electrophoresis to quantify HIV-1 p24 antigen. Method A pair of anti-p24 monoclonal antibodies (mAbs were used in BCA assays to capture HIV-1 p24 antigen in a sandwich format and allowed for the quantitative measurement of captured p24 using PCR and gel electrophoresis. The first 1 G12 mAb was coated on microplate wells or magnetic microparticles (MMPs to capture free p24 antigens. Captured p24 in turn captured 1D4 mAb coated gold nanoparticle probes (GNPs containing double-stranded DNA oligonucleotides. One strand of the oligonucleotides was covalently immobilized whereas the unbound complimentary bio-barcode DNA strand could be released upon heating. The released bio-barcode DNA was amplified by PCR, electrophoresed in agarose gel and quantified. Results The in-house ELISA assay was found to quantify p24 antigen with a limit of detection (LOD of 1,000 pg/ml and a linear range between 3,000 and 100,000 pg/ml. In contrast, the BCA-based microplate method yielded an LOD of 1 pg/ml and a linear detection range from 1 to 10,000 pg/ml. The BCA-based MMP method yielded an LOD of 0.1 pg/ml and a linear detection range from 0.1 to 1,000 pg/ml. Conclusions When combined with PCR and simple gel electrophoresis, BCA-based microplate and MMPs assays can be used to quantify HIV-1 p24 antigen. These methods are 3–4 orders of magnitude more sensitive than our in-house ELISA-based assay and may provide a useful approach to detect p24 in patients newly infected

  13. The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

    Directory of Open Access Journals (Sweden)

    Burger Marieta

    2011-02-01

    Full Text Available Abstract Background One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1 and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1, an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.

  14. Transmission of GB Virus Type C via Transfusion in a Cohort of HIV-Infected Patients

    Science.gov (United States)

    Petersen, M.; Rutherford, G.; Busch, M.; Assmann, S.; Stapleton, J. T.; Custer, B.

    2012-01-01

    Background. GB virus C (GBV-C) infection is transmitted by blood exposure and associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients. Methods. We used a limited-access database from the National Heart Lung and Blood Institute’s Viral Activation Transfusion Study, a randomized controlled trial of leukoreduced versus nonleukoreduced transfusions received by HIV-infected, transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers in pretransfusion and posttransfusion samples. We estimated the risk of acquiring GBV-C RNA and predictors of GBV-C acquisition, using pooled logistic regression. Results. GBV-C RNA was detected ≤120 days following the first transfusion in 22 (7.5%) of 294 subjects who were GBV-C negative before transfusion. The risk of GBV-C RNA acquisition increased with each unit transfused (odds ratio, 1.09; 95% confidence interval, 1.06–1.11). Lower baseline HIV load and use of antiretroviral therapy were associated with subsequent GBV-C RNA acquisition, after control for units of blood transfused. Leukoreduced status of transfused units was not associated with GBV-C transmission. Conclusions. Blood transfusion is associated with a significant risk of GBV-C acquisition among HIV-infected patients. Transmission of GBV-C by blood transfusion was inversely related to HIV load. PMID:22438325

  15. HIV Information and Behavioral Skills Moderate the Effects of Relationship Type and Substance Use on HIV Risk Behaviors Among African American Youth

    Science.gov (United States)

    Byck, Gayle R.; Newcomb, Michael E.; Henry, David; Bolland, John; Dick, Danielle

    2013-01-01

    Abstract The HIV/AIDS epidemic is disproportionately impacting young African Americans. Efforts to understand and address risk factors for unprotected sex in this population are critical in improving prevention efforts. Situational risk factors, such as relationship type and substance use before sex, are in need of further study. This study explored how established cognitive predictors of risky sexual behavior moderated the association between situational factors and unprotected sex among low-income, African American adolescents. The largest main effect on the number of unprotected sex acts was classifying the relationship as serious (event rate ratio=10.18); other significant main effects were alcohol use before sex, participant age, behavioral skills, and level of motivation. HIV information moderated the effect of partner age difference, motivation moderated the effects of partner age difference and drug use before sex, and behavioral skills moderated the effects of alcohol and drug use before sex. This novel, partnership-level approach provides insight into the complex interactions of situational and cognitive factors in sexual risk taking. PMID:23701198

  16. Genetic characterization of HIV type 1 from migrant workers in three South African gold mines.

    Science.gov (United States)

    Bredell, H; Williamson, C; Sonnenberg, P; Martin, D J; Morris, L

    1998-05-20

    The phylogenetic relationships between 44 HIV-1 isolates from 43 infected subjects employed by three adjacent South African gold mines were investigated. The patients were migrant workers originating from rural areas of South Africa and the neighboring countries of Lesotho, Botswana, Swaziland, and Mozambique. Proviral HIV-1 DNA was subtyped using a heteroduplex mobility assay (HMA) based on the 700-bp V3-V5 region of the env gene. DNA sequence analysis was used to confirm the subtype designation and to determine phylogenetic relationships between isolates. All 44 HIV-1 isolates were identified as env subtype C using both HMA and phylogenetic analysis. These isolates did not show a distinct phylogenetic relatedness based on the geographic origins of the migrant workers or show close homology to other subtype C sequences from southern Africa or India. However, five clusters of closely related sequences were identified, mainly involving miners of disparate geographic origins, suggesting possible epidemiological linkage in these few cases. The characteristic tetrapeptide sequence, GPGQ, at the tip of the V3 loop of subtype C viruses was conserved in the predicted amino acid sequences of most isolates. The heterogeneity of HIV-1 sequences among migrant workers in a mining cohort suggests multiple introductions of HIV-1 subtype C into this population that are not apparently linked to the geographic origins of the patients.

  17. Behavioral intention to take up different types of HIV testing among men who have sex with men who were never-testers in Hong Kong.

    Science.gov (United States)

    Wang, Zixin; Lau, Joseph T F; She, Rui; Ip, Mary; Jiang, Hui; Ho, Shara P Y; Yang, XueYing

    2018-01-01

    Human immunodeficiency virus (HIV) testing is an important global prevention strategy but underutilized by local men who have sex with men (MSM). This study investigated the prevalence of behavioral intention to take up HIV testing (specific or any type), in the next six months among MSM who had not been tested for HIV in the last three years (never-testers) in Hong Kong. The data was based on 141 never-testers of 430 MSM who completed the anonymous baseline telephone survey of an ongoing randomized controlled trial from January 2015 to August 2015. Only 17.7% of them showed strong intention to take up any type of HIV testing in the next six months. Adjusted analysis showed that perceived benefit of HIV testing (adjusted odds ratio [AOR]: 1.29, 95% confidence interval [CI]: 1.01, 1.66), perceived psychological barriers of HIV testing (AOR: 0.85, 95%CI: 0.73, 1.00), and perceived self-efficacy in taking up HIV testing (AOR: 1.28, 95%CI: 1.07, 1.52) were significantly associated with behavioral intention to take up any HIV testing. Perceived cue to action from non-governmental organization staff was positively associated with a marginal p-value of 0.077 (AOR: 2.37, 95%CI: 0.97, 5.77). It is warranted to strengthen perceived benefit, remove psychological barriers, and increase perceived self-efficacy related to HIV testing. Innovative and effective health promotions are greatly needed to increase HIV testing coverage among never-testers.

  18. Performance characteristics of serologic tests for human immunodeficiency virus type 1 (HIV-1) antibody among Minnesota blood donors. Public health and clinical implications.

    Science.gov (United States)

    MacDonald, K L; Jackson, J B; Bowman, R J; Polesky, H F; Rhame, F S; Balfour, H H; Osterholm, M T

    1989-04-15

    To evaluate performance characteristics of sequential enzyme immunoassay (EIA) and Western blot human immunodeficiency virus type 1 (HIV-1) antibody testing in a low-risk population. Three-year prospective study of a selected sample from a community-based population. Two blood collection facilities in Minnesota. Minnesota blood donors. During the study period, 630,190 units of blood (donations) from an estimated 290,110 Minnesota-resident donors were screened for HIV-1 antibody. Seventeen Minnesota-resident donors were identified as positive for HIV-1 antibody. Sixteen donors were available for follow-up HIV-1 culture: all were culture positive. The other donor, who was not available for follow-up culture, was likely infected with HIV-1 based on a history of high-risk behavior and positive serologic findings for hepatitis B surface antigen. Using 95% binomial confidence intervals, performance characteristics for sequential EIA and Western blot HIV-1 antibody serology were as follows: false-positive rate by number of donations, 0% to 0.0006%; specificity by number of donations, 99.9994% to 100%; predictive value of a positive test, 81% to 100%. In this low-risk population, the false-positive rate of serologic tests for HIV-1 antibody, using HIV-1 culture as the definitive standard for infection status, was extremely low and test specificity was extremely high.

  19. HIV-1 and herpes simplex virus type-2 genital shedding among co-infected women using self-collected swabs in Chiang Rai, Thailand.

    Science.gov (United States)

    Forhan, S E; Dunne, E F; Sternberg, M R; Whitehead, S J; Leelawiwat, W; Thepamnuay, S; Chen, C; Evans-Strickfaden, Tt; McNicholl, J M; Markowitz, L E

    2012-08-01

    We analysed 528 genital self-collected swabs (SCS) from 67 HIV-1 and herpes simplex virus type-2 (HSV-2) co-infected women collected during the placebo month of a randomized crossover clinical trial of suppressive acyclovir in Chiang Rai, Thailand. In this first longitudinal study of HIV-1 and HSV-2 co-infected women using genital SCS specimens, we found frequent mucosal HIV-1 shedding. Overall, 372 (70%) swabs had detectable HIV-1 RNA with median HIV-1 viral load of 2.61 log(10) copies/swab. We found no statistically significant association between detectable HIV-1 RNA and HSV-2 DNA in the same SCS specimen (adjusted odds ratio [aOR] 1.40; 95% confidence intervals [CI], 0.78-2.60, P = 0.25). Only baseline HIV-1 plasma viral load was independently associated with genital HIV-1 RNA shedding (aOR, 7.6; 95% CI, 3.3-17.2, P genital sampling, and inclusion of genital sites other than the cervix.

  20. A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1

    Science.gov (United States)

    Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

    2009-09-01

    Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.

  1. Association of HIV infection with distribution and viral load of HPV types in Kenya: a survey with 820 female sex workers

    Directory of Open Access Journals (Sweden)

    Delva Wim

    2010-01-01

    Full Text Available Abstract Background Human papillomavirus (HPV and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low. Methods Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional Pap smears. Results Median age of the 820 participants was 28 years (inter-quartile range [IQR] = 24-36 years. One third of women were HIV infected (283/803; 35.2% and these women were y more likely to have abnormal cervical cytology than HIV-negative women (27%, 73/269, versus 8%, 42/503; P P P = 0.98. High-risk HPV types other than 16 and 18 were common in LSIL (74.7%; 56/75 and HSIL (84.6%; 22/26; even higher among HIV-infected women. Conclusions HIV-infected sex workers had almost four-fold higher prevalence of high-risk HPV, raised viral load and more precancerous lesions. HPV 16 and HPV 18, preventable with current vaccines, were associated with cervical disease, though other high-risk types were commoner. HIV-infected sex workers likely contribute disproportionately to HPV transmission dynamics in the general population. Current efforts to prevent HIV and HPV are inadequate. New interventions are required and improved implementation of existing strategies.

  2. Human Immunodeficiency Virus (HIV types Western blot (WB band profiles as potential surrogate markers of HIV disease progression and predictors of vertical transmission in a cohort of infected but antiretroviral therapy naïve pregnant women in Harare, Zimbabwe

    Directory of Open Access Journals (Sweden)

    Chirenje Mike Z

    2011-01-01

    Full Text Available Abstract Background Expensive CD4 count and viral load tests have failed the intended objective of enabling access to HIV therapy in poor resource settings. It is imperative to develop simple, affordable and non-subjective disease monitoring tools to complement clinical staging efforts of inexperienced health personnel currently manning most healthcare centres because of brain drain. Besides accurately predicting HIV infection, sequential appearance of specific bands of WB test offers a window of opportunity to develop a less subjective tool for monitoring disease progression. Methods HIV type characterization was done in a cohort of infected pregnant women at 36 gestational weeks using WB test. Student-t test was used to determine maternal differences in mean full blood counts and viral load of mothers with and those without HIV gag antigen bands. Pearson Chi-square test was used to assess differences in lack of bands appearance with vertical transmission and lymphadenopathy. Results Among the 64 HIV infected pregnant women, 98.4% had pure HIV-1 infection and one woman (1.7% had dual HIV-1/HIV-2 infections. Absence of HIV pol antigen bands was associated with acute infection, p = 0.002. All women with chronic HIV-1 infection had antibody reactivity to both the HIV-1 envelope and polymerase antigens. However, antibody reactivity to gag antigens varied among the women, being 100%, 90%, 70% and 63% for p24, p17, p39 and p55, respectively. Lack of antibody reactivity to gag p39 antigen was associated with disease progression as confirmed by the presence of lymphadenopathy, anemia, higher viral load, p = 0.010, 0.025 and 0.016, respectively. Although not statistically significant, women with p39 band missing were 1.4 times more likely to transmit HIV-1 to their infants. Conclusion Absence of antibody reactivity to pol and gag p39 antigens was associated with acute infection and disease progression, respectively. Apart from its use in HIV disease

  3. GB virus type C interactions with HIV: the role of envelope glycoproteins

    OpenAIRE

    Mohr, Emma L.; Stapleton, Jack T.

    2009-01-01

    GB virus C/hepatitis G virus (GBV-C/HGV) is the most closely related human virus to hepatitis C virus (HCV). GBV-C is lymphotropic and not associated with any known disease, although it is associated with improved survival in HIV-infected individuals. In peripheral blood mononuclear cells, GBV-C induces the release of soluble ligands for HIV entry receptors (RANTES, MIP-1a, MIP-1b and SDF-1), suggesting that GBV-C may interact with lymphocytes to induce a chemokine and/or cytokine milieu that...

  4. New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands Clinic, Harare, Zimbabwe: retrospective cohort analysis.

    Science.gov (United States)

    Chimbetete, Cleophas; Mugglin, Catrina; Shamu, Tinei; Kalesan, Bindu; Bertisch, Barbara; Egger, Matthias; Keiser, Olivia

    2017-07-01

    To assess the incidence and associated factors of Type 2 Diabetes Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. We analysed data of all HIV-infected patients older than 16 years who attended Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers patients whose random blood sugar is higher than 11.1 mmol/l and which is confirmed by a fasting blood sugar higher than 7.0 mmol/l to have T2DM. T2DM is also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors for developing T2DM were identified using Cox proportional hazard models adjusted for confounding. Missing baseline BMI data were multiply imputed. Results are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). Data for 4,110 participants were included: 67.2% were women; median age was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337) cells/mm3 . The proportion of participants with hypertension at baseline was 15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57 patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per 1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR: 1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30 kg/m2 ) (aHR=2.26, 95% CI: 1.17-4.36), age >40 years (aHR=2.16, 95% CI: 1.22-3.83) and male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO clinical stage) were not independent risk factors for developing T2DM. Although the incidence of T2DM in this HIV cohort was lower than that has been observed in others, our results show that risk factors for developing T2DM among HIV-infected people are similar to those of the general population. HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care that includes better health services for prevention, early

  5. 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.

  6. Human immunodeficiency virus type 1 (HIV-1 genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    JC Couto-Fernandez

    2005-02-01

    Full Text Available In order to assess the human immunodeficiency virus type 1 (HIV-1 drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation. Viral resistance genotyping was performed using ViroSeqTM Genotyping System (Celera Diagnostic-Abbott, US. The HIV-1 subtyping based on polymerase (pol gene sequences (protease and reverse transcriptase-RT regions was as follows: subtype B (91.2%, subtype F (4.9%, and B/F viral recombinant forms (3.3%. The subtype C was identified in two patients (0.4% and the recombinant CRF_02/AG virus was found infecting one patient (0.2%. The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.

  7. 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.

  8. Neutralizing antibody and perinatal transmission of human immunodeficiency virus type 1. New York City Perinatal HIV Transmission Collaborative Study Group.

    Science.gov (United States)

    Hengel, R L; Kennedy, M S; Steketee, R W; Thea, D M; Abrams, E J; Lambert, G; McDougal, J S

    1998-04-10

    The major immunologic determinants for perinatal transmission of human immunodeficiency virus type 1 (HIV-1) remain largely unknown. The presence of maternal neutralizing antibodies has been proposed as an explanation for why the majority of infants born to untreated HIV-1-infected women do not become infected. Using maternal and infant specimens collected as part of a longitudinal cohort study of perinatal transmission in New York City between 1991 and 1995, we successfully obtained primary viral isolates from 10 of 20 perinatally nontransmitting (NTR) women, 14 of 20 perinatally transmitting (TR) women, and 13 of 13 of their HIV-1-infected infants. Neutralizing antibody titers were then determined using a titer reduction assay. TR and NTR women did not differ in their ability to neutralize autologous virus or laboratory strains LAI and MN. Infant viruses were not less sensitive to neutralization by maternal sera than autologous viruses. Similarly, TR and NTR isolates were neutralized equally well using a reference serum with broad neutralizing ability. Finally, a heteroduplex tracking assay (HTA) was used to analyze the degree of viral homology within 13 TR maternal-infant pairs. In eight pairs, maternal and infant isolates were highly homologous. In five pairs, lesser degrees of homology were observed, consistent with perinatal transmission of a minor species. However, these isolates were no more or less resistant to maternal sera than were homologous isolates. Thus we found no association between the presence of neutralizing antibody in maternal sera as measured by a titer reduction neutralization (inactivation) assay and perinatal transmission of HIV-1.

  9. Hydrolysis of RNA/DNA hybrids containing nonpolar pyrimidine isosteres defines regions essential for HIV type 1 polypurine tract selection.

    Science.gov (United States)

    Rausch, Jason W; Qu, Jin; Yi-Brunozzi, Hye Young; Kool, Eric T; Le Grice, Stuart F J

    2003-09-30

    Both x-ray crystallography and chemical footprinting indicate that bases of the HIV type 1 (HIV-1) polypurine tract (PPT)-containing RNA/DNA hybrid deviate from standard Watson-Crick base pairing. However, the contribution of these structural anomalies to the accuracy of plus-strand primer selection by HIV-1 reverse transcriptase is not immediately clear. To address this issue, DNA templates harboring single and pairwise non-hydrogen-bonding isosteres of cytosine (2-fluoro-4-methylbenzene deoxyribonucleoside) and thymine (2,4-difluoro-5-methylbenzene deoxyribonucleoside) were synthesized and hybridized to PPT-containing RNA primers as a means of locally removing hydrogen bonding and destabilizing paired structure. Cleavage of these hybrids was examined with p66/p51 HIV-1 reverse transcriptase and a mutant carrying an alteration in the p66 RNase H primer shown to specifically impair PPT processing. Analog insertion within the PPT (rG):(dC) and central (rA):(dT) tracts repositioned the RNase H domain such that the RNA/DNA hybrid was cleaved 3-4 bp from the site of insertion, a distance corresponding closely to the spatial separation between the catalytic center and RNase H primer grip. However, PPT processing was significantly impaired when the junction between these tracts was substituted. Substitutions within the upstream (rA):(dT) tract, where maximum distortion had previously been observed, destroyed PPT processing. Collectively, our scanning mutagenesis approach implicates multiple regions of the PPT in the accuracy with which it is excised from (+) U3 RNA and DNA, and also provides evidence for close cooperation between the RNase H primer grip and catalytic center in achieving this cleavage.

  10. Immunological predictors of survival in HIV type 2-infected rural villagers in Guinea-Bissau

    DEFF Research Database (Denmark)

    Jaffar, Shabbar; Van der Loeff, Maarten Schim; Eugen-Olsen, Jesper

    2005-01-01

    %, and plasma viral load were associated independently with survival in multivariate analyses. Neopterin and suPAR did not reach statistical significance. These findings suggest that immune activation is central to the pathogenesis of HIV. They also have important implications for resource-poor settings where...

  11. Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy.

    NARCIS (Netherlands)

    Beukel, CJ van den Bout-va; Fievez, L.; Michels, M.; Sweep, F.C.; Hermus, A.R.M.M.; Bosch, M.E.; Burger, D.M.; Bravenboer, B.; Koopmans, P.P.; Ven, A.J.A.M. van der

    2008-01-01

    Vitamin D regulates bone metabolism but has also immunoregulatory properties. In HIV-infected patients bone disorders are increasingly observed. Furthermore, low 1,25(OH)(2)D(3) levels have been associated with low CD4(+) counts, immunological hyperactivity, and AIDS progression rates. Few studies

  12. The effect of cholecalciferol and calcitriol on biochemical bone markers in HIV type 1-infected males

    DEFF Research Database (Denmark)

    Bang, Ulrich Christian; Kolte, Lilian; Hitz, Mette

    2013-01-01

    conducted a placebo-controlled randomized study running for 16 weeks including 61 HIV-1-infected males, of whom 51 completed the protocol. Nineteen participants were randomized to daily treatment with (A) 0.5-1.0 μg calcitriol and 1,200 IU (30 μg) cholecalciferol, 17 participants to (B) 1,200 IU...

  13. Plasma concentrations of generic lopinavir/ritonavir in HIV type-1-infected individuals

    NARCIS (Netherlands)

    van der Lugt, Jasper; Lange, Joep; Avihingsanon, Anchalee; Ananworanich, Jintanat; Sealoo, Siriporn; Burger, David; Gorowara, Meena; Phanuphak, Praphan; Ruxrungtham, Kiat

    2009-01-01

    Generic drugs can contribute to access to treatment for HIV-infected patients. However quality and safety remains an issue of concern. Therefore, we evaluated minimal plasma concentrations and short-term safety of a generic lopinavir/ritonavir 200/50 mg tablet formulation. In a single-centre

  14. Plasma concentrations of generic lopinavir/ritonavir in HIV type-1-infected individuals.

    NARCIS (Netherlands)

    Lugt, J. van der; Lange, J.; Avihingsanon, A.; Ananworanich, J.; Sealoo, S.; Burger, D.M.; Gorowara, M.; Phanuphak, P.; Ruxrungtham, K.

    2009-01-01

    BACKGROUND: Generic drugs can contribute to access to treatment for HIV-infected patients. However quality and safety remains an issue of concern. Therefore, we evaluated minimal plasma concentrations and short-term safety of a generic lopinavir/ritonavir 200/50 mg tablet formulation. METHODS: In a

  15. Anti-human immunodeficiency virus type 1 (HIV-1) activity of lectins from Narcissus species.

    Science.gov (United States)

    López, Susana; Armand-Ugon, Mercedes; Bastida, Jaume; Viladomat, Francesc; Esté, José A; Stewart, Derek; Codina, Carles

    2003-02-01

    Mannose-specific lectins (MSLs) were isolated from bulbs of fifteen wild Narcissus species growing in Spain and assayed for their HIV-1 infection inhibitory activity in MT-4 cells and compared to the Narcissus pseudonarcissus agglutinin (NPA), the commercially available MSL obtained from daffodils. Almost all the tested MSLs were found to be active, showing EC50 values (microg/mL) similar to that of NPA, with some being comparable to those obtained with dextran sulfate without significant cytotoxicity. However, on a molar basis almost all of the MSLs tested exhibited lower EC50 values than dextran sulfate whilst six MSLs had values lower than AZT. The most efficacious anti-HIV-1 activity was exhibited by the Narcissus tortifolious MSL, which was 10- (microg/mL) and 100- (molarity) fold more potent than dextran sulfate. Significantly, although this MSL was 15-fold less potent than AZT in terms of quantity (microg/mL), it was 68-fold more potent on a molar basis. The antiviral indices, a ratio of the concentrations that produce cytotoxicity and HIV-1 replication, were calculated and three of the MSLs, N. confusus, N. leonensis and N. tortifolius reported 1.5-, 2- and 8.5-fold greater AI values than dextran sulfate or AZT. Comparison of MSL haemagglutination activities (HAA) to their anti-HIV-1 activities showed that there was no significant correlation. It was suggested that this may be due to a dissociation between both activities as a consequence of multiple isolectin composition.

  16. Dyadic dynamics of HIV risk among transgender women and their primary male sexual partners: the role of sexual agreement types and motivations.

    Science.gov (United States)

    Gamarel, Kristi E; Reisner, Sari L; Darbes, Lynae A; Hoff, Colleen C; Chakravarty, Deepalika; Nemoto, Toru; Operario, Don

    2016-01-01

    Transgender women - individuals assigned a male sex at birth who identify as women, female, or on the male-to-female trans feminine spectrum - are at high-risk of HIV worldwide. Prior research has suggested that transgender women more frequently engage in condomless sex with primary cisgender (i.e., non-transgender) male partners compared with casual or paying partners, and that condomless sex in this context might be motivated by relationship dynamics such as trust and intimacy. The current study examined sexual agreement types and motivations as factors that shape HIV risk behaviors in a community sample of 191 transgender women and their cisgender primary male partners who completed a cross-sectional survey. Overall, 40% of couples had monogamous, 15% open, and 45% discrepant sexual agreements (i.e., partners disagreed on their type of agreement). Actor-partner interdependence models were fit to examine the influence of sexual agreement type and motivations on extra-dyadic HIV risk (i.e., condomless sex with outside partners) and intra-dyadic HIV serodiscordant risk (i.e., condomless sex with serodiscordant primary partners). For male partners, extra-dyadic risk was associated with their own and their partners' sexual agreement motives, and male partners who engaged in extra-dyadic HIV risk had an increased odds of engaging in HIV serodiscordant intra-dyadic risk. Study findings support inclusion of the male partners of transgender women into HIV prevention efforts. Future research is warranted to explore the interpersonal and social contexts of sexual agreement types and motivations in relationships between transgender women and their male partners to develop interventions that meet their unique HIV prevention needs.

  17. Intrahost and interhost variability of the HIV type 1 nef gene in Brazilian children.

    Science.gov (United States)

    Cavalieri, Elizabeth; Florido, Camila; Leal, Elcio; Machado, Daisy Maria; Camargo, Michelle; Diaz, Ricardo S; Janini, Luiz Mario

    2009-11-01

    Many aspects of HIV-1 pathogenesis are affected by Nef protein activity, and efforts have been made to study variation in the nef gene and how that variation relates to disease outcome. We studied the genetic diversity of the nef gene in distinct clones obtained from the same patient (intrahost) and in sequences obtained from different hosts (interhost). The set of sequences analyzed was obtained from HIV-1-infected Brazilian children and contained 112 clones from 25 children (intrahost samples), as well as 55 sequences from epidemiologically unlinked children (interhost samples). We found extensive site polymorphisms and amino acid length variations, mainly in the amino terminal region of the nef gene, between the myristoylation motif (MGxxxS) and the MHC-1 downregulation motif (Rxx). Analysis of the sequences deposited in the Los Alamos HIV sequences database ( www.hiv.lanl.gov ) indicated that the most frequent motif at the MHC-1 downregulation site in the subtype B strain is R(86%)A(64%)E(82%) (n = 1040) and R(78%)T(74%)E(56%) in the subtype C strain (n = 549). Conversely, the Brazilian subtype B isolates presented the motif R(81%)T(62%)E(67%) at this site (n = 64). A detailed analysis of selective pressures identified a concentration of codons under strong positive selection in the amino terminal region of the nef gene. We also determined that different sites are under positive selection in the subtype B and subtype C viruses. The amino acid composition in the MHC-1 downregulation motif of the nef gene in our sequences may indicate a distinct adaptive pattern of HIV-1 subtype B to the Brazilian host population.

  18. Lipidomic dataset of plasma from patients infected with wild type and nef-deficient HIV-1 strain

    Directory of Open Access Journals (Sweden)

    Peter Meikle

    2016-03-01

    Full Text Available Previous in vitro and in vivo studies demonstrated that HIV protein nef plays a key role in impairing cellular and systemic cholesterol metabolism in HIV disease, but clinical support for these findings is lacking. Here we present the data of comparative lipidomic analysis (330 lipid species of plasma samples from HIV-negative subjects, patients infected with WT HIV-1 strain and patients infected with nef-deficient strain of HIV-1. We determine which effects of HIV on plasma lipidome are explained by the presence of nef. The data can be used to evaluate cardiovascular risk in HIV disease and to assess the role of nef in HIV-induced disturbances in systemic lipid metabolism. The full impact of nef deficiency on lipid and lipoprotein metabolism in HIV-infected patients is presented in the accompanying study “Lipid Metabolism in Patients Infected with Nef-deficient HIV-1 Strain” [1].

  19. Low prevalence of antiretroviral resistance among HIV type 1-positive prisoners in the Southeast United States.

    Science.gov (United States)

    Menezes, Prema; Rosen, David; Wohl, David A; Kiziah, Nichole; Sebastian, Joseph; Eron, Joseph J; White, Becky

    2013-01-01

    Drug-resistant HIV complicates management of HIV infection. Although an estimated 14% of all HIV-positive persons pass through a prison or jail in the United States each year, little is known about the overall prevalence of antiretroviral (ARV) resistance in incarcerated persons. All genotypic sequence data on HIV-positive prisoners in the North Carolina (NC) Department of Corrections (DOC) were obtained from LabCorp. Screening for major resistance mutations in protease (PI) and reverse transcriptase (NRTI and NNRTI) was done using Genosure and the Stanford HIV Database. For subjects with multiple genotype reports, each mutation was counted only once and considered present on all subsequent genotypes. Between October 2006 and February 2010, the NC DOC incarcerated 1,911 HIV(+) individuals of whom 19.2% (n=367) had at least one genotype performed. The overall prevalence of a major resistance mutation was 28.3% (95% CI 23.7, 33.0). Among prisoners ever exposed to an ARV during incarceration (n=329) prevalence of a major resistance mutation was 29.8% (95% CI 24.9, 34.7); resistance by class was 20.4% (95% CI 16.0, 24.7) for NRTIs, 19.8% (95% CI 15.5, 24.1) for NNRTIs, and 8.8% (95% CI 5.8,11.9) for PIs. Single class drug resistance was most prevalent at 14.2% (10.2,17.7) followed by dual 12.5% (I8.9,16.0) and triple class 3.3% (1.4,5.3) resistance. The three most prevalent mutations were K103N 15.8% (12.0, 20.2), M184V 14.3% (10.7,18.5), and M41L 4.9% (2.8,7.8). In the NC DOC ARV resistance prevalence, dual and triple class drug resistance was moderate over the study period. Resistance to PIs was lower than NNRTIs and NRTIs, likely reflecting higher usage of these two classes or a lower barrier to resistance.

  20. The power of siblings and caregivers: under-explored types of social support among children affected by HIV and AIDS.

    Science.gov (United States)

    Sharer, Melissa; Cluver, Lucie; Shields, Joseph J; Ahearn, Frederick

    2016-03-01

    Children affected by HIV and AIDS have significantly higher rates of mental health problems than unaffected children. There is a need for research to examine how social support functions as a source of resiliency for children in high HIV-prevalence settings such as South Africa. The purpose of this research was to explore how family social support relates to depression, anxiety, and post-traumatic stress (PTS). Using the ecological model as a frame, data were drawn from a 2011 cross-sectional study of 1380 children classified as either orphaned by AIDS and/or living with an AIDS sick family member. The children were from high-poverty, high HIV-prevalent rural and urban communities in South Africa. Social support was analyzed in depth by examining the source (e.g. caregiver, sibling) and the type (e.g. emotional, instrumental, quality). These variables were entered into multiple regression analyses to estimate the most parsimonious regression models to show the relationships between social support and depression, anxiety, and PTS symptoms among the children. Siblings emerged as the most consistent source of social support on mental health. Overall caregiver and sibling support explained 13% variance in depression, 12% in anxiety, and 11% in PTS. Emotional support was the most frequent type of social support associated with mental health in all regression models, with higher levels of quality and instrumental support having the strongest relation to positive mental health outcomes. Although instrumental and quality support from siblings were related to positive mental health, unexpectedly, the higher the level of emotional support received from a sibling resulted in the child reporting more symptoms of depression, anxiety, and PTS. The opposite was true for emotional support provided via caregivers, higher levels of this support was related to lower levels of all mental health symptoms. Sex was significant in all regressions, indicating the presence of moderation.

  1. CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Piekarz Andrew D

    2012-07-01

    Full Text Available Abstract Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2 to bind to N-type voltage-activated calcium channels (CaV2.2 [Brittain et al. Nature Medicine 17:822–829 (2011]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of

  2. Identification of a Novel Scaffold for Allosteric Inhibition of Wild Type and Drug Resistant HIV-1 Reverse Transcriptase by Fragment Library Screening

    NARCIS (Netherlands)

    Geitmann, M.; Elinder, M; Seeger, C; Brandt, P; de Esch, I.J.P.; Danielson, U.H.

    2011-01-01

    A novel scaffold inhibiting wild type and drug resistant variants of human immunodeficiency virus type 1 reverse transcriptase (HIV-1RT) has been identified in a library consisting of 1040 fragments. The fragments were significantly different from already known non-nucleoside reverse transcriptase

  3. Immunogenicity and safety of two doses of catch-up immunization with Haemophilus influenzae type b conjugate vaccine in Indian children living with HIV.

    Science.gov (United States)

    Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Saha, Malay K; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Das, Ranjan Saurav; Mallick, Mausom; Mandal, Sutapa

    2016-04-27

    Children living with HIV are at increased risk of disease from Haemophilus influenzae type b (Hib). Data are limited on the immunogenicity of a two-dose, catch-up schedule for Hib conjugate vaccine (HibCV) among HIV-infected children accessing antiretroviral therapy (ART) late. The objectives of the study were to: (1) evaluate baseline immunity to Hib and the immunogenicity and safety of two doses of HibCV among HIV-infected Indian children; and (2) document the threshold antibody level required to prevent Hib colonization among HIV-infected children following immunization. We conducted a prospective cohort study among HIV-infected children 2-15 years of age and HIV-uninfected children 2-5 years of age. HIV-infected children received two doses of HibCV and uninfected children received one. Serum anti-Hib PRP IgG antibodies were measured at baseline and two months after immunization in the HIV-infected children. Nasopharyngeal (NP) swabs were collected at baseline and follow-up. 125 HIV-infected and 44 uninfected children participated. 40% of HIV-infected children were receiving ART and 26% had a viral load >100,000 copies/mL. The geometric mean concentration of serum anti-Hib PRP antibody increased from 0.25 μg/mL at baseline to 2.65 μg/mL after two doses of HibCV, representing a 10.6-fold increase (pchildren mounted an immune response. Moderate or severe immune suppression, trimethoprim/sulfamethoxazole prophylaxis, and lower baseline antibody levels were associated with lower post-vaccine serum anti-Hib PRP IgG antibodies. A serum anti-Hib PRP IgG antibody level ≥ 3.3 μg/mL was protective against Hib NP colonization. There were no differences in adverse events between HIV-infected and uninfected children. Including a catch-up immunization schedule for older HIV infected children in countries introducing Hib vaccines is important. Older HIV-infected children with delayed access to ART and without suppressed viral loads mounted an adequate immune response

  4. Introduction of HIV type 1 into an isolated population: molecular epidemiologic study from Greenland

    DEFF Research Database (Denmark)

    Madsen, Tina V; Leitner, Thomas; Lohse, Nicolai

    2007-01-01

    Database. All Greenlandic sequences were subtype B except one sequence found to be a recombinant (probably CRF13). Sequence clusters in the phylogenetic trees indicated that there had been at least nine introductions of HIV-1 into Greenland. One cluster, supported by bootstrap values of 81, 76, and 96......% for gag, pol, and env, corresponding to one introduction, contained 53 (76%) of the Greenland patients. The patients in the cluster differed from other Greenlandic patients in epidemiological parameters. Two distinct subgroups within the main cluster were concentrated around the two largest Greenlandic...... towns. Although HIV-1 has been introduced into Greenland at least nine times, only one introduction gave rise to an epidemic. The phylogeny did not indicate from where the main Greenland cluster had been introduced as no database sequence from outside Greenland was genetically close to this cluster...

  5. Differential effects of P-class versus other CpG oligodeoxynucleotide classes on the impaired innate immunity of plasmacytoid dendritic cells in HIV type 1 infection.

    Science.gov (United States)

    Donhauser, Norbert; Helm, Martin; Pritschet, Kathrin; Schuster, Philipp; Ries, Moritz; Korn, Klaus; Vollmer, Jörg; Schmidt, Barbara

    2010-02-01

    Abstract Human plasmacytoid dendritic cells (PDC) are the major producers of type I interferons (IFN) after stimulation with CpG oligodeoxynucleotides (ODN). HIV-1-infected patients show a deficit in PDC numbers and function with progression of disease. CpG ODN appear to be attractive therapeutics to support the impaired innate immunity in HIV-1 infection. PDC counts, phenotype, and function were analyzed in 23 HIV-infected untreated individuals and 16 controls. Markers for migration (CCR7), activation (CD80), maturation (CD83), and endocytosis (BDCA2) were evaluated at baseline and 20 h after in vitro stimulation with class A, B, C, and P ODN. PDC counts and the expression of BDCA2 on these cells were significantly lower in HIV-1-infected subjects compared to controls (both p classes (A > P > C > B) in patients and controls (p class ODN may be effective in reversing this innate immune defect, which should be further evaluated in vivo.

  6. Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env

    DEFF Research Database (Denmark)

    Mens, Helene; Jørgensen, Louise Bruun; Kronborg, Gitte

    2009-01-01

    BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure....... METHODS: Individuals with MDR HIV-1 receiving therapy for > or =3 months were included. CD4+ T-cell count slopes and pol and clonal env sequences were determined. Genetic analyses were performed using distance-based and maximum likelihood methods. Synonymous mutations rates of env were used to estimate...... for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response (P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes (r= -0.56, P=0.04 and r...

  7. Impact of acyclovir on genital and plasma HIV-1 RNA, genital herpes simplex virus type 2 DNA, and ulcer healing among HIV-1-infected African women with herpes ulcers: a randomized placebo-controlled trial.

    Science.gov (United States)

    Mayaud, Philippe; Legoff, Jérôme; Weiss, Helen A; Grésenguet, Gérard; Nzambi, Khonde; Bouhlal, Hicham; Frost, Eric; Pépin, Jacques; Malkin, Jean-Elie; Hayes, Richard J; Mabey, David C W; Bélec, Laurent

    2009-07-15

    Little is known about the impact of episodic treatment of herpes on human immunodeficiency virus type 1 (HIV-1). Women from Ghana and the Central African Republic who had genital ulcers were enrolled in a randomized, double-blind, placebo-controlled trial of acyclovir plus antibacterials and were monitored for 28 days. Ulcer etiologies and detection of lesional HIV-1 RNA were determined by polymerase chain reaction (PCR). Cervicovaginal HIV-1 RNA and herpes simplex virus type 2 (HSV-2) DNA and plasma HIV-1 RNA were quantitated by real-time PCR. Primary analyses included 118 HIV-1-infected women with HSV-2 ulcers (54 of whom were given acyclovir and 64 of whom were given placebo). Acyclovir had little impact on (1) detection of cervicovaginal HIV-1 RNA (risk ratio [RR], 0.96; 95% confidence interval [CI], 0.8-1.2) at day 7 of treatment, (2) the mean cervicovaginal HIV-1 RNA load (-0.06 log(10) copies/mL; 95% CI, -0.4 to 0.3 log(10) copies/mL) at day 7 of treatment, or (3) the plasma HIV-1 RNA load (+0.09 log(10) copies/mL; 95% CI, -0.1 to 0.3 log(10) copies/mL) at day 14 of treatment. At day 7, women receiving acyclovir were less likely to have detectable lesional HIV-1 RNA (RR, 0.70; 95% CI, 0.4-1.2) or cervicovaginal HSV-2 DNA (RR, 0.69; 95% CI, 0.4-1.3), had a lower quantity of HSV-2 DNA (-0.99 log(10) copies/mL; 95% CI, -1.8 to -0.2 log(10) copies/mL), and were more likely to have a healed ulcer (RR, 1.26; 95% CI, 0.9-1.9). Episodic therapy for herpes reduced the quantity of cervicovaginal HSV-2 DNA and slightly improved ulcer healing, but it did not decrease genital and plasma HIV-1 RNA loads. ClinicalTrials.gov identifier NCT00158483 .

  8. Evaluation of circulating natural type 1 interferon-producing cells in HIV/GBV-C and HIV/HCV coinfected patients: a preliminary study.

    Science.gov (United States)

    Haji Molla Hoseini, Mostafa; Pourfathollah, Ali-Akbar; Mohraz, Minoo; Soheili, Zahra; Amini, Sedigheh; Aghaiepour, Mahnaz; Samiee, Shahram; Nikoogoftar, Mahin; Meshkani, Reza

    2007-11-01

    GB virus-C (GBV-C) is a flavivirus that probably influences HIV infection-associated disease among HIV/GBV-C coinfected patients and inhibits the progression of HIV infection to AIDS. To address the possibility of immune-modulating effects of GBV-C coinfection in HIV patients, we evaluated interferon-producing cells in HIV/GBV-C coinfected patients and compared them to HIV-infected patients. We performed a pilot study to enumerate interferon-producing cell count by two-color flow cytometric analysis and also for determining the frequency of ongoing GBV-C and HCV infection among patients infected with HIV. Then, 83 asymptomatic HIV-positive patients were considered for evaluation of interferon-producing cells. Eighty three patients were stratified in four groups according to the HCV and GBV-C infection status: patients infected with HCV and GBV-C (GBV-C+/HCV+), patients infected with GBV-C but not with HCV (GBV-C+/HCV-), patients infected with HCV but not with GBV-C (GBV-C-/HCV+), and patients not infected by GBV-C and HCV (GBV-C-/HCV-). GBV-C was detected in plasma samples from 15.5% of HIV-infected patients and the frequency of HCV infection was 47.5%. Interferon-producing cells in GBV-C coinfected individuals revealed a wider range of numbers; however, there was no significant difference in the interferon-producing cell count among HIV-infected individuals. It does not appear that GBV-C coinfection affects generation or redistribution of interferon-producing cells in HIV-infected patients with relatively intact immune system.

  9. Mortality and morbidity among HIV type-1-infected patients during the first 5 years of a multicountry HIV workplace programme in Africa

    NARCIS (Netherlands)

    van der Borght, Stefaan F.; Clevenbergh, Philippe; Rijckborst, Henk; Nsalou, Paul; Onyia, Ngozi; Lange, Joep M.; Rinke de Wit, Tobias F.; van der Loeff, Maarten F. Schim

    2009-01-01

    BACKGROUND: This study aimed to evaluate the effectiveness of an HIV workplace programme in sub-Saharan Africa. METHODS: The international brewing company, Heineken, introduced an HIV workplace programme in its African subsidiaries in 2001. Beneficiaries from 16 sites in 5 countries were eligible.

  10. Rise in seroprevalence of herpes simplex virus type 1 among highly sexual active homosexual men and an increasing association between herpes simplex virus type 2 and HIV over time (1984-2003)

    NARCIS (Netherlands)

    Smit, Colette; Pfrommer, Christiaan; Mindel, Adrian; Taylor, Janette; Spaargaren, Joke; Berkhout, Ben; Coutinho, Roel; Dukers, Nicole H. T. M.

    2007-01-01

    OBJECTIVES: Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) are both highly prevalent. The rate of genital HSV-1 transmission is reportedly increasing over time. HSV-2 is considered to be an important risk factor for HIV transmission. We therefore studied changes in the HSV-1 and HSV-2

  11. Seroepidemiology of herpes simplex virus type 2 (HSV2) in HIV infected patients in Kermanshah-Iran

    OpenAIRE

    Janbakhash, Alireza; Mansouri, Feizollah; Vaziri, Siavash; Sayad, Babak; Afsharian, Mandana; Abedanpor, Ahmadreza

    2012-01-01

    Background: HSV2 has an important role in acquiring and transmitting HIV through genital ulcers. This study was conducted to determine the prevalence of this virus in HIV infected subject in Kermanshah, Iran.

  12. Molecular Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 in Yaoundé, Cameroon: Evidence of Major Drug Resistance Mutations in Newly Diagnosed Patients Infected with Subtypes Other than Subtype B▿

    Science.gov (United States)

    Ndembi, Nicaise; Abraha, Awet; Pilch, Heather; Ichimura, Hiroshi; Mbanya, Dora; Kaptue, Lazare; Salata, Robert; Arts, Eric J.

    2008-01-01

    Prior to current studies on the emergence of drug resistance with the introduction of antiretroviral therapy (ART) in Cameroon, we performed genotypic analysis on samples from drug-naïve, human immunodeficiency virus (HIV)-infected individuals in this country. Of the 79 HIV type 1 (HIV-1) pol sequences analyzed from Cameroonian samples, 3 (3.8%) were identified as HIV-1 group O, 1 (1.2%) was identified as an HIV-2 intergroup B/A recombinant, and the remaining 75 (95.0%) were identified as HIV-1 group M. Group M isolates were further classified as subtypes A1 (n = 4), D (n = 4), F2 (n = 6), G (n = 12), H (n = 2), and K (n = 1) and as circulating recombinant forms CRF02_AG (n = 41), CRF11_cpx (n = 1), and CRF13_cpx (n = 2). Two pol sequences were identified as unique recombinant forms of CRF02_AG/F2 (n = 2). M46L (n = 2), a major resistance mutation associated with resistance to protease inhibitors, was observed in 2/75 (2.6%) group M samples. Single mutations associated with resistance to nucleoside reverse transcriptase inhibitors (T215Y/F [n = 3]) and nonnucleoside reverse transcriptase inhibitors (V108I [n = 1], L100I [n = 1], and Y181C [n = 2]) were observed in 7 of 75 (9.3%) group M samples. None of the patients had any history of ART exposure. Population surveillance of transmitted HIV drug resistance is required and should be included to aid in the development of appropriate guidelines. PMID:17855574

  13. Adhesion and fusion efficiencies of human immunodeficiency virus type 1 (HIV-1) surface proteins

    Science.gov (United States)

    Dobrowsky, Terrence M.; Rabi, S. Alireza; Nedellec, Rebecca; Daniels, Brian R.; Mullins, James I.; Mosier, Donald E.; Siliciano, Robert F.; Wirtz, Denis

    2013-10-01

    In about half of patients infected with HIV-1 subtype B, viral populations shift from utilizing the transmembrane protein CCR5 to CXCR4, as well as or instead of CCR5, during late stage progression of the disease. How the relative adhesion efficiency and fusion competency of the viral Env proteins relate to infection during this transition is not well understood. Using a virus-cell fusion assay and live-cell single-molecule force spectroscopy, we compare the entry competency of viral clones to tensile strengths of the individual Env-receptor bonds of Env proteins obtained from a HIV-1 infected patient prior to and during coreceptor switching. The results suggest that the genetic determinants of viral entry were predominantly enriched in the C3, HR1 and CD regions rather than V3. Env proteins can better mediate entry into cells after coreceptor switch; this effective entry capacity does not correlate with the bond strengths between viral Env and cellular receptors.

  14. Use of Capillary Electrophoresis to Study the Binding Interaction of Aptamers with Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT : Studying the Binding Interaction of Wild-Type, K103N, and Double Mutant (K103N/Y181C) HIV-1 RT with Aptamers by Performing the Capillary Electrophoresis.

    Science.gov (United States)

    Aeksiri, Niran; Warakulwit, Chompunuch; Hannongbua, Supa; Unajak, Sasimanas; Choowongkomon, Kiattawee

    2017-06-01

    A number of nucleic acid aptamers with high affinities to human immunodeficiency virus reverse transcriptase (HIV-1 RT) are currently known. They can potentially be developed as broad-spectrum antiviral drugs, but there is little known about their binding interaction with mutant HIV-1 RT. Therefore, we utilized non-equilibrium capillary electrophoresis of equilibrium mixture (NECEEM) to study the interaction of three HIV-1 RTs (wild type, K103N, and double mutant (K103N/Y181C)) with RT1t49 and RT12 aptamers. This approach was used to study and evaluate the K d values of these molecules. The results showed that the K d values of the tested aptamers were lower than that of the DNA substrate. The results also pointed out that RT1t49 could bind with all HIV-1 RTs and compete with the DNA substrate at the active site. Moreover, we studied the binding stoichiometry of HIV-1 RT using aptamers as probes. The findings showed evidence of two binding stoichiometries with HIV-1 RT and the RT12 aptamer but only one binding stoichiometry for RT1t49. In addition, RT1t49 could bind specifically with the wild-type, K103N, and double mutants in Escherichia coli lysate. This result also indicated that the aptamer could detect HIV-1 RT in the presence of E. coli lysate.

  15. The HIV type 1 epidemic in Belarus: predominance of Eastern European subtype A strains and circulation of subtype B viruses

    NARCIS (Netherlands)

    Lazouskaya, Natallia V.; Eremin, Vladimir F.; Adema, Karen W.; Gasich, Elena L.; Baan, Elly; Lukashov, Vladimir V.

    2005-01-01

    To study the molecular epidemiology of HIV-1 in Belarus, where the rapid spread of HIV-1 has been registered since 1996, we obtained HIV-1 sequences from 30 individuals living in five cities in both the main geographic areas of the epidemic (Gomel and Minsk regions) and territories where spreading

  16. Phylodynamic and Phylogeographic Patterns of the HIV Type 1 Subtype F1 Parenteral Epidemic in Romania

    Science.gov (United States)

    Hué, Stéphane; Buckton, Andrew J.; Myers, Richard E.; Duiculescu, Dan; Ene, Luminita; Oprea, Cristiana; Tardei, Gratiela; Rugina, Sorin; Mardarescu, Mariana; Floch, Corinne; Notheis, Gundula; Zöhrer, Bettina; Cane, Patricia A.; Pillay, Deenan

    2012-01-01

    Abstract In the late 1980s an HIV-1 epidemic emerged in Romania that was dominated by subtype F1. The main route of infection is believed to be parenteral transmission in children. We sequenced partial pol coding regions of 70 subtype F1 samples from children and adolescents from the PENTA-EPPICC network of which 67 were from Romania. Phylogenetic reconstruction using the sequences and other publically available global subtype F sequences showed that 79% of Romanian F1 sequences formed a statistically robust monophyletic cluster. The monophyletic cluster was epidemiologically linked to parenteral transmission in children. Coalescent-based analysis dated the origins of the parenteral epidemic to 1983 [1981–1987; 95% HPD]. The analysis also shows that the epidemic's effective population size has remained fairly constant since the early 1990s suggesting limited onward spread of the virus within the population. Furthermore, phylogeographic analysis suggests that the root location of the parenteral epidemic was Bucharest. PMID:22251065

  17. Hematologic toxicity associated with interferon-based hepatitis C therapy in HIV type 1-coinfected subjects.

    Science.gov (United States)

    Behler, Caroline M; Vittinghoff, Eric; Lin, Feng; Chung, Raymond T; Peters, Marion G; Robbins, Gregory K; Volberding, Paul A

    2007-05-15

    This study investigates whether dose modifications for adverse hematologic effects or the use of hematopoietic growth factors influenced the outcome of therapy for hepatitis C virus (HCV) infection in patients who were coinfected with HCV and human immunodeficiency virus (HIV) and who were participants in a randomized, controlled trial. Subjects were randomized to receive ribavirin plus interferon-alfa-2a (IFN-alfa-2a) or pegylated IFN-alfa-2a for a total of 48 weeks. Doses were modified for a number of adverse effects (including hematologic toxicity), and hematopoietic growth factors were administered at the discretion of the physician. Associations of dose modifications or initiation of hematopoietic growth factor support with treatment outcomes were determined by standard statistical methods. One hundred thirty-three subjects were included in this study. Subjects treated with pegylated IFN-alfa-2a were more likely to have had dose modifications (dose reduction or discontinuation) than were those treated with IFN-alfa-2a. By multivariate analysis, treatment with pegylated IFN-alfa-2a is associated with higher sustained virologic and/or histologic response. Dose modifications for nonhematologic toxicity are independently associated with lower sustained virologic and/or histologic responses. Although hematologic toxicity was not directly associated with clinical outcome in this analysis, use of hematopoietic growth factors was associated with an increased sustained virologic and/or histologic response. Dose modifications for anti-HCV therapy may adversely affect the outcome of treatment of HCV in individuals who are coinfected with HIV. The use of hematopoietic growth factor support may be associated with an improved clinical response to therapy.

  18. Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

    DEFF Research Database (Denmark)

    Costagliola, Dominique; Ledergerber, Bruno; Torti, Carlo

    2013-01-01

    Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure....

  19. Risk factors for anal human papillomavirus infection type 16 among HIV-positive men who have sex with men in San Francisco

    Science.gov (United States)

    Hernandez, Alexandra L.; Efird, Jimmy T.; Holly, Elizabeth A.; Berry, J. Michael; Jay, Naomi; Palefsky, Joel M.

    2015-01-01

    Background and Objective HIV-positive men who have sex with men (MSM) are at high risk of anal cancer compared with the general population. Human papillomavirus (HPV) infection, particularly HPV 16, is causally associated with anal cancer. However, risk factors for anal HPV 16 infection are poorly understood. We determined the prevalence and risk factors for anal HPV 16 infection in a population of HIV-positive MSM, most of whom were being treated with antiretroviral therapy. Design Cross-sectional data from the baseline visit of a 4-year prospective cohort study. Methods 348 HIV-positive MSM were recruited in San Francisco and received a detailed sexual behavior risk-factor questionnaire. An anal swab was used to collect specimens for HPV type-specific DNA testing using L1 HPV DNA PCR. We used log-binomial multivariable models to determine risk factors for anal HPV 16 infection. Results 92% of HIV-positive MSM had at least one anal HPV type, 80% had at least one oncogenic HPV type and 42% had HPV 16. Non-Hispanic white race and higher level of education were associated with a decreased risk of HPV 16 infection. A higher number of total male partners was associated with HPV 16 (RR: 1.6, 95%CI 1.1–2.4, p=0.01) for 201–1000 partners compared with 1–200. Injection drug use (IDU) was independently associated with anal HPV 16 infection (RR: 1.5, 95%CI 1.2–1.9, p=0.003). Conclusions The prevalence of anal HPV infection, including HPV 16, is high in HIV-positive MSM. HIV-positive MSM should be counseled about the risk associated with increased partners and IDU. PMID:23614994

  20. Protein-Protein Interaction between Surfactant Protein D and DC-SIGN via C-Type Lectin Domain Can Suppress HIV-1 Transfer.

    Science.gov (United States)

    Dodagatta-Marri, Eswari; Mitchell, Daniel A; Pandit, Hrishikesh; Sonawani, Archana; Murugaiah, Valarmathy; Idicula-Thomas, Susan; Nal, Béatrice; Al-Mozaini, Maha M; Kaur, Anuvinder; Madan, Taruna; Kishore, Uday

    2017-01-01

    Surfactant protein D (SP-D) is a soluble C-type lectin, belonging to the collectin (collagen-containing calcium-dependent lectin) family, which acts as an innate immune pattern recognition molecule in the lungs at other mucosal surfaces. Immune regulation and surfactant homeostasis are salient functions of SP-D. SP-D can bind to a range of viral, bacterial, and fungal pathogens and trigger clearance mechanisms. SP-D binds to gp120, the envelope protein expressed on HIV-1, through its C-type lectin or carbohydrate recognition domain. This is of importance since SP-D is secreted by human mucosal epithelial cells and is present in the female reproductive tract, including vagina. Another C-type lectin, dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), present on the surface of the DCs, also binds to HIV-1 gp120 and facilitates viral transfer to the lymphoid tissues. DCs are also present at the site of HIV-1 entry, embedded in vaginal or rectal mucosa. In the present study, we report a direct protein-protein interaction between recombinant forms of SP-D (rfhSP-D) and DC-SIGN via their C-type lectin domains. Both SP-D and DC-SIGN competed for binding to immobilized HIV-1 gp120. Pre-incubation of human embryonic kidney cells expressing surface DC-SIGN with rfhSP-D significantly inhibited the HIV-1 transfer to activated peripheral blood mononuclear cells. In silico analysis revealed that SP-D and gp120 may occupy same sites on DC-SIGN, which may explain the reduced transfer of HIV-1. In summary, we demonstrate, for the first time, that DC-SIGN is a novel binding partner of SP-D, and this interaction can modulate HIV-1 capture and transfer to CD4+ T cells. In addition, the present study also reveals a novel and distinct mechanism of host defense by SP-D against HIV-1.

  1. Seroprevalence of Herpes Simplex Virus type-2 (HSV-2) among pregnant women who participated in a national HIV surveillance activity in Haiti.

    Science.gov (United States)

    Domercant, Jean Wysler; Jean Louis, Frantz; Hulland, Erin; Griswold, Mark; Andre-Alboth, Jocelyne; Ye, Tun; Marston, Barbara J

    2017-08-18

    Herpes simplex virus type 2 (HSV-2), one the most common causes of genital ulcers, appears to increase both the risk of HIV acquisition and HIV transmission. HSV-2/HIV co-infection among pregnant women may increase the risk of perinatal transmission of HIV. This study describes rates of HSV-2 among pregnant women in Haiti and HSV-2 test performance in this population. Unlinked residual serum specimens from the 2012 National HIV and Syphilis Sentinel Surveillance Survey among pregnant women in Haiti were tested using two commercial kits (Focus HerpeSelect, Kalon) for HSV-2 antibodies. We evaluated rates of HSV-2 seropositivity and HSV-2/HIV co-infection, associations between HSV-2 and demographic characteristics using multivariable Cox proportional hazards modeling, and HSV-2 test performance in this population. Serum samples from 1000 pregnant women (all 164 HIV positive and 836 random HIV negative) were selected. The overall weighted prevalence of HSV-2 was 31.4% (95% CI: 27.7-35.4) and the prevalence of HIV-positivity among HSV-2 positive pregnant women was five times higher than the prevalence among HSV-2 negative women (4.8% [95% CI: 3.9-6.0] vs. 0.9% [95% CI: 0.6-1.3], respectively). Factors significantly associated with HSV-2 positivity were HIV-positivity (PR: 2.27 [95% CI: 1.94-2.65]) and older age (PRs: 1.41 [95% CI: 1.05-1.91] for 20-24 years, 1.71 [95% CI:1.13-2.60] for 30-34 years, and 1.55 [95% CI: 1.10-2.19] for 35 years or greater]), while rural residence was negatively associated with HSV-2 positivity (PR 0.83 [95% CI: 0.69-1.00]), after controlling for other covariables. For this study a conservative Focus index cutoff of 3.5 was used, but among samples with a Focus index value ≥2.5, 98.4% had positive Kalon tests. The prevalence of HSV-2 is relatively high among pregnant women in Haiti. Public health interventions to increase access to HSV-2 screening in antenatal services are warranted.

  2. Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.

    Directory of Open Access Journals (Sweden)

    Gareth A D Hardy

    Full Text Available Type-I interferon (IFN-I has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFNα in HCV-infected subjects to model the effect of IFNα on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p = 0.012, and IFNα was the predominant IFN-I subtype correlating with IFN-I bioactivity (r = 0.658, p<0.001. IFNα was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFNα mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFNα in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p = 0.003 and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p = 0.009. In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p = 0.003. These studies identify IFNα derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection.

  3. Evaluating HIV Prevention Programs: Herpes Simplex Virus Type 2 Antibodies as Biomarker for Sexual Risk Behavior in Young Adults in Resource-Poor Countries.

    Directory of Open Access Journals (Sweden)

    Juliane Behling

    Full Text Available Measuring effectiveness of HIV prevention interventions is challenged by bias when using self-reported knowledge, attitude or behavior change. HIV incidence is an objective marker to measure effectiveness of HIV prevention interventions, however, because new infection rates are relatively low, prevention studies require large sample sizes. Herpes simplex virus type 2 (HSV-2 is similarly transmitted and more prevalent and could thus serve as a proxy marker for sexual risk behavior and therefore HIV infection.HSV-2 antibodies were assessed in a sub-study of 70,000 students participating in an education intervention in Western Province, Kenya. Feasibility of testing for HSV-2 antibodies was assessed comparing two methods using Fisher's exact test. Three hundred and ninety four students (aged 18 to 22 years were randomly chosen from the cohort and tested for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Out of these, 139 students were tested for HSV-2 with ELISA and surveyed for sexual risk behavior and 89 students were additionally tested for HSV-2 with a point-of-contact (POC test.Prevalence rates were 0.5%, 1.8%, 0.3% and 2.3% for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, respectively. Prevalence of HSV-2 antibodies was 3.4 % as measured by POC test (n=89 and 14.4 % by ELISA (n=139. Specificity of the POC test compared with ELISA was 100%, and the sensitivity only 23.1%. Associations between self-reported sexual behavior and HSV-2 serostatus could not be shown.Associations between self-reported sexual risk behavior and HSV-2 serostatus could not be shown, probably due to social bias in interviews since its transmission is clearly linked. HSV-2 antibody testing is feasible in resource-poor settings and shows higher prevalence rates than other sexually transmitted diseases thus representing a potential biomarker for evaluation of HIV prevention interventions.

  4. Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env

    DEFF Research Database (Denmark)

    Mens, Helene; Jørgensen, Louise Bruun; Kronborg, Gitte

    2009-01-01

    BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure....... METHODS: Individuals with MDR HIV-1 receiving therapy for > or =3 months were included. CD4+ T-cell count slopes and pol and clonal env sequences were determined. Genetic analyses were performed using distance-based and maximum likelihood methods. Synonymous mutations rates of env were used to estimate...... viral replication. RESULTS: Of 1,000 patients treated between 1995 and 2003, 72 individuals fulfilled the definition for triple-class failure, but 25 were non-compliant, 21 were successfully resuppressed and 3 had died or quit therapy. Of the 23 that fulfilled study criteria, 16 had samples available...

  5. Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus.

    Science.gov (United States)

    Behl, Tapan; Kotwani, Anita; Kaur, Ishneet; Goel, Heena

    2015-05-15

    Nephrogenic diabetes insipidus is a clinical sub-type of a diversely expounded disorder, named diabetes insipidus. It is characterized by inability of the renal cells to sense and respond to the stimulus of vasopressin. Amongst its various etiologies, one of the most inevitable causes includes lithium-induced instigation. Numerous studies reported marked histological damage to the kidneys upon long-term treatment with lithium. The recent researches have hypothesized many lithium-mediated mechanisms to explain the damage and dysfunction caused in the kidneys following lithium exposure. These mechanisms, widely, intend to justify the lithium-induced electrolyte imbalance, its interference with some vital proteins and a specific steroidal hormone, obstruction caused to a certain imperative transducer pathway and the renal tubular acidification defect produced on its prolonged therapy. Thorough study of such mechanisms aids in better understanding of the role of lithium in the pathophysiology of this disorder. Hence, the ameliorated knowledge regarding disease-pathology might prove beneficial in developing therapies that aim on disrupting the various lithium-mediated pathways. Hence, this may effectively lead to the demonstration of a novel treatment for nephrogenic diabetes insipidus, which is, at present, limited to the use of diuretics which block lithium reuptake into the body. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans.

    Science.gov (United States)

    Thanos, S M; Halliday, G M; Damian, D L

    2012-09-01

    The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown. To determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans. Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression. High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045). While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  7. Total Raltegravir Concentrations in Cerebrospinal Fluid Exceed the 50-Percent Inhibitory Concentration for Wild-Type HIV-1▿

    OpenAIRE

    Croteau, David; Letendre, Scott; Best, Brookie M.; Ellis,Ronald J.; Breidinger, Sheila; Clifford, David; Collier, Ann; Gelman, Benjamin; Marra, Christina; Mbeo, Gilbert; McCutchan, Allen; Morgello, Susan; Simpson, David; Way, Lauren; Vaida, Florin

    2010-01-01

    HIV-associated neurocognitive disorders continue to be common. Antiretrovirals that achieve higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV and improved cognition. The objective of this study was to measure total raltegravir (RAL) concentrations in CSF and to compare them with matched concentrations in plasma and in vitro inhibitory concentrations. Eighteen subjects with HIV-1 infection were enrolled based on the use of RAL-containing regimens and ...

  8. Therapeutic Vaccination Using Cationic Liposome-Adjuvanted HIV Type 1 Peptides Representing HLA-Supertype-Restricted Subdominant T Cell Epitopes

    DEFF Research Database (Denmark)

    Román, Victor Raúl Gómez; Jensen, Kristoffer Jarlov; Jensen, Sanne Skov

    2013-01-01

    We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity...... is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against...

  9. Maintenance of syncytium-inducing phenotype of HIV type 1 is associated with positively charged residues in the HIV type 1 gp120 V2 domain without fixed positions, elongation, or relocated N-linked glycosylation sites

    NARCIS (Netherlands)

    Cornelissen, M.; Hogervorst, E.; Zorgdrager, F.; Hartman, S.; Goudsmit, J.

    1995-01-01

    The prevalence of HIV-1 sequences of the envelope domains V1V2 and V3 was analyzed by RT-PCR amplification. Two distinct biological phenotypes of HIV-1 have been described: the nonsyncytium-inducing (NSI) phenotype, best characterized by the inability to infect MT-2 cells, and the syncytium-inducing

  10. HIV/AIDS and the Flu

    Science.gov (United States)

    ... Influenza Types Seasonal Avian Swine/Variant Pandemic Other HIV/AIDS and the Flu Questions & Answers Language: English ( ... people with HIV and AIDS. Should people with HIV/AIDS receive the inactivated influenza vaccine? People with ...

  11. A systematic review of the effects of different types of therapeutic exercise on physiologic and functional measurements in patients with HIV/AIDS.

    Science.gov (United States)

    Gomes-Neto, Mansueto; Conceição, Cristiano Sena; Oliveira Carvalho, Vitor; Brites, Carlos

    2013-01-01

    Several studies have reported the benefits of exercise training for adults with HIV, although there is no consensus regarding the most efficient modalities. The aim of this study was to determine the effects of different types of exercise on physiologic and functional measurements in patients with HIV using a systematic strategy for searching randomized controlled trials. The sources used in this review were the Cochrane Library, EMBASE, MEDLINE, and PEDro from 1950 to August 2012. We selected randomized controlled trials examining the effects of exercise on body composition, muscle strength, aerobic capacity, and/or quality of life in adults with HIV. Two independent reviewers screened the abstracts using the Cochrane Collaboration's protocol. The PEDro score was used to evaluate methodological quality. In total, 29 studies fulfilled the inclusion criteria. Individual studies suggested that exercise training contributed to improvement of physiologic and functional parameters, but that the gains were specific to the type of exercise performed. Resistance exercise training improved outcomes related to body composition and muscle strength, with little impact on quality of life. Aerobic exercise training improved body composition and aerobic capacity. Concurrent training produced significant gains in all outcomes evaluated, although moderate intensity and a long duration were necessary. We concluded that exercise training was shown to be a safe and beneficial intervention in the treatment of patients with HIV.

  12. A quantum mechanic/molecular mechanic study of the wild-type and N155S mutant HIV-1 integrase complexed with diketo acid.

    Science.gov (United States)

    Alves, Cláudio Nahum; Martí, Sergio; Castillo, Raquel; Andrés, Juan; Moliner, Vicent; Tuñón, Iñaki; Silla, Estanislao

    2008-04-01

    Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes essential for effective viral replication. Recently, mutation studies have been reported that have shown that a certain degree of viral resistance to diketo acids (DKAs) appears when some amino acid residues of the IN active site are mutated. Mutations represent a fascinating experimental challenge, and we invite theoretical simulations for the disclosure of still unexplored features of enzyme reactions. The aim of this work is to understand the molecular mechanisms of HIV-1 IN drug resistance, which will be useful for designing anti-HIV inhibitors with unique resistance profiles. In this study, we use molecular dynamics simulations, within the hybrid quantum mechanics/molecular mechanics (QM/MM) approach, to determine the protein-ligand interaction energy for wild-type and N155S mutant HIV-1 IN, both complexed with a DKA. This hybrid methodology has the advantage of the inclusion of quantum effects such as ligand polarization upon binding, which can be very important when highly polarizable groups are embedded in anisotropic environments, for example in metal-containing active sites. Furthermore, an energy terms decomposition analysis was performed to determine contributions of individual residues to the enzyme-inhibitor interactions. The results reveal that there is a strong interaction between the Lys-159, Lys-156, and Asn-155 residues and Mg(2+) cation and the DKA inhibitor. Our calculations show that the binding energy is higher in wild-type than in the N155S mutant, in accordance with the experimental results. The role of the mutated residue has thus been checked as maintaining the structure of the ternary complex formed by the protein, the Mg(2+) cation, and the inhibitor. These results might be useful to design compounds with more interesting anti-HIV-1 IN activity on the basis of its three-dimensional structure.

  13. Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD

  14. Prevention of mother-to-child transmission of HIV type 1: the role of neonatal and infant prophylaxis.

    Science.gov (United States)

    Hurst, Stacey A; Appelgren, Kristie E; Kourtis, Athena P

    2015-02-01

    The prevention of mother-to-child transmission (PMTCT) of HIV is one of the great public health successes of the past 20 years. Much concerted research efforts and dedicated work have led to the achievement of very low rates of PMTCT of HIV in settings that can implement optimal prophylaxis. Though several implementation challenges remain, global elimination of pediatric HIV infection seems now more than ever to be an attainable goal. Often overlooked, the role of prophylaxis of the newborn is nevertheless a very important component of PMTCT. In this paper, we focus on the role of neonatal and infant prophylaxis, discuss mechanisms of protection, and present the clinical trial-generated evidence that led to the current recommendations for preventing infections in breastfed and non-breastfed infants. PMTCT of HIV should not end at birth; a continuum of care extending postpartum and postnatally is required to minimize the risk of new pediatric HIV infections.

  15. Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters

    Science.gov (United States)

    Azizi, Ali; Anderson, David E; Ghorbani, Masoud; Gee, Katrina; Diaz-Mitoma, Francisco

    2006-01-01

    Background One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters. Results We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E Conclusion Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity. PMID:17076905

  16. Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters

    Directory of Open Access Journals (Sweden)

    Ghorbani Masoud

    2006-10-01

    Full Text Available Abstract Background One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters. Results We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E Conclusion Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120 resulted in a quantitative improvement in vaccine-induced immunity.

  17. Seroepidemiology of herpes simplex virus type 2 (HSV2) in HIV infected patients in Kermanshah-Iran.

    Science.gov (United States)

    Janbakhash, Alireza; Mansouri, Feizollah; Vaziri, Siavash; Sayad, Babak; Afsharian, Mandana; Abedanpor, Ahmadreza

    2012-01-01

    HSV2 has an important role in acquiring and transmitting HIV through genital ulcers. This study was conducted to determine the prevalence of this virus in HIV infected subject in Kermanshah, Iran. This descriptive study was performed among 170 HIV positive patients (case group) and 165 non-HIV cases (control group)) referred to Behavioral Counseling Center of Kermanshah, western of Iran. For the evaluation of HSV2 infection, blood sample was obtained and assessed for IgG antibody of HSV2 using ELISA method. The data were collected and analyzed. Out of 170 cases, 11 were seropositive for HSV2 (6.5%) in case group and 2 of 165 (1.21%) in control group (p=0.015). Seropositivity was 17.6% in female and 5.2% in male, 59% under and 8% age over 40. In HIV infected subjects, seroprevalence in female was 17.6% and in male was 5.2% (p=0.083). It can be derived that the seroprevalence of HSV2 in HIV positive patients in our region is relatively low. Hence, we do not recommend that HSV2 needs to be considered in HIV pretreatment evaluation program.

  18. 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, ...

  19. Transmission of nevirapine-resistant HIV type 1 via breast milk to infants after single-dose nevirapine in Beira, Mozambique.

    Science.gov (United States)

    Micek, Mark A; Dross, Sandra; Blanco, Ana Judith; Beck, Ingrid A; Matunha, Laurinda; Seidel, Kristy; Montoya, Pablo; Matediana, Eduardo; Gantt, Soren; Gloyd, Stephen; Frenkel, Lisa

    2014-08-15

    Acquisition of nevirapine (NVP)-resistant human immunodeficiency virus type 1 (HIV-1) by breast-feeding infants after receipt of single-dose NVP to prevent mother-to-child transmission is not well defined. A prospective observational study of 307 infants evaluated the rate of breast milk transmission of NVP-resistant HIV and the concentrations of mutants over time. NVP resistance was detected in 9 of 24 infants (37.5%; 95% confidence interval, 18.8%-59.4%) infected via breast milk. Eight had a pure mutant HIV population at the time infection was first detected, and majority mutant populations persisted in all 6 infants with follow-up specimens. Infection of breast-feeding infants with NVP-resistant HIV resulted in mutants persisting as the dominant virus, which may indefinitely compromise treatment with NVP-based antiretroviral regimens. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. 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 ...

  1. Nadir CD4+, religion, antiretroviral therapy, incidence of type 2 diabetes mellitus, and increasing rates of obesity among black Africans with HIV disease.

    Science.gov (United States)

    Mandina Ndona, Madone; Longo-Mbenza, Benjamin; Wumba, Roger; Tandu Umba, Barthelemy; Buassa-Bu-Tsumbu, Baudouin; Mbula Mambimbi, Marcel; Wobin, Thaddée Odio; Mbungu Fuele, Simon

    2012-01-01

    The purpose of this study was to determine the cross-sectional association between some sociodemographic factors and antiretroviral therapy (ART), as well as the incidence and predictors of type 2 diabetes mellitus among Central Africans with human immunodeficiency virus (HIV) disease. This study had a cross-sectional design and was a prospective analysis of 102 patients with HIV disease (49 on ART versus 53 not on ART) in Kinshasa, Democratic Republic of Congo, between 2004 and 2008. A Cox regression model was used to assess for any relationship between type 2 diabetes and exposure to combination ART without protease inhibitors, after adjusting for known risk factors for type 2 diabetes, nadir CD4 and CD8 levels, viral load, marital status, and religion. Unexpectedly elevated rates of smoking, excess alcohol intake, and ART-related total, abdominal, and peripheral obesity were observed in our study group of HIV patients. At the end of follow-up, five patients were diagnosed with type 2 diabetes (incidence rate 4.9%, 9.8 per 1000 person-years). Univariate risk factors for type 2 diabetes were male gender (relative risk [RR] 1.1, 95% confidence interval [CI] 1.01-1.4; P = 0.019), traditional religion versus new charismatic religion (RR 1.1, 95% CI 1.01-1.3; P = 0.046), exposure to ART (RR 1.1, 95% CI 1.002-1.3; P = 0.034), and single status (RR 6.2, 95% CI 1.5-15; P = 0.047). In multivariate analysis, strong significant independent predictors of type 2 diabetes were belonging to a traditional religion (HR 2.1, 95% CI 1.1-4.2; P = 0.036) and a relative increase in nadir CD4 cell count (beta coefficient 0.003; P religion status appear to be the strongest independent predictors of type 2 diabetes.

  2. Human papilloma virus types in the oral and cervical mucosa of HIV-positive South African women prior to antiretroviral therapy.

    Science.gov (United States)

    Richter, Karin L; van Rensburg, Estrelita Janse; van Heerden, Willie F P; Boy, Sonja C

    2008-10-01

    To evaluate the prevalence of human papilloma virus (HPV) infection and types in the oral and cervix mucosa of treatment-naïve HIV-1-positive women with CD4 counts less than 300 cells per ml with no HPV-associated oral lesions. Oral epithelium was harvested from the buccal mucosa and lateral borders of the tongue and cervical samples were collected from the endocervical area of 30 women, 22-64 years old. Cytobrush Plus cell collectors were used for sampling both anatomical areas. Genital pathology, obstetric and gynaecological history, co-morbid disease, hormone therapy, sexual behavior and smoking history were assessed via physical examination and clinical interviews. Special investigations included cervical Papanicolau smears, CD4 counts and HIV-1 viral loads. The linear array HPV test was used to determine HPV genotypes present in the specimens. Oral HPV were identified in 20% (n = 6) of the patients, of which two had infection with two HPV types. Genital HPV was found in 96.7% (n = 29) of the women, of which only 14 had cytological abnormalities on Papanicolau smear. Infection with multiple HPV types were present in 93.1% (n = 27) of the patients, with an average of four HPV types per individual. South African HIV-positive women with CD4 counts less than 300 cells per ml have a significant risk of cervical HPV strains and multiple strain infection of the cervix. The prevalence of HPV in normal oral mucosa was low but high-risk types were present. Limited correlation between oral HPV types and those identified in the cervical mucosa was found.

  3. The EVVA Cohort Study: Anal and Cervical Type-Specific Human Papillomavirus Prevalence, Persistence, and Cytologic Findings in Women Living With HIV.

    Science.gov (United States)

    de Pokomandy, Alexandra; Kaufman, Elaina; de Castro, Christina; Mayrand, Marie-Hélène; Burchell, Ann N; Klein, Marina; Charest, Louise; Auger, Manon; Rodrigues-Coutlée, Sophie; Coutlée, François

    2017-08-15

    The risk of anal cancer due to high-risk human papillomavirus (HR-HPV) is higher in women living with human immunodeficiency virus (HIV) than in the general population. We present findings of cervical and anal HPV and cytologic tests at baseline in the EVVA cohort study and HPV persistence data 6 months after baseline. Semiannual visits included questionnaires, chart reviews, cervical/anal cytologic and cervical/anal HPV testing for 2 years. Genotyping for 36 HPV genotypes was performed using the Roche Linear Array HPV genotyping test. A total of 151 women living with HIV were recruited. At baseline, 75% had anal HPV, 51% had anal HR-HPV, 50% had cervical HPV, and 29% had cervical HR-HPV. Anal HPV-16 and HPV-51 were more frequent in women born in Canada (31% and 29%, respectively, compared with ≤16% for other women). Most anal HR-HPV types detected at 6 months (57%-93%) were persistent from baseline. Findings of anal cytologic tests were abnormal for 37% of women. Anal HPV is highly prevalent in women living with HIV, and type distribution varies by place of birth. High-resolution anoscopy was indicated in more than one third of results. As anal cancer is potentially preventable, these important findings need to be considered when selecting the best approach for anal cancer screening programs.

  4. Estimation of the Binding Free Energy of AC1NX476 to HIV-1 Protease Wild Type and Mutations Using Free Energy Perturbation Method.

    Science.gov (United States)

    Ngo, Son Tung; Mai, Binh Khanh; Hiep, Dinh Minh; Li, Mai Suan

    2015-10-01

    The binding mechanism of AC1NX476 to HIV-1 protease wild type and mutations was studied by the docking and molecular dynamics simulations. The binding free energy was calculated using the double-annihilation binding free energy method. It is shown that the binding affinity of AC1NX476 to wild type is higher than not only ritonavir but also darunavir, making AC1NX476 become attractive candidate for HIV treatment. Our theoretical results are in excellent agreement with the experimental data as the correlation coefficient between calculated and experimentally measured binding free energies R = 0.993. Residues Asp25-A, Asp29-A, Asp30-A, Ile47-A, Gly48-A, and Val50-A from chain A, and Asp25-B from chain B play a crucial role in the ligand binding. The mutations were found to reduce the receptor-ligand interaction by widening the binding cavity, and the binding propensity is mainly driven by the van der Waals interaction. Our finding may be useful for designing potential drugs to combat with HIV. © 2015 John Wiley & Sons A/S.

  5. Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Nawei; Zhang, Zhenyu [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Feng, Shan [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China); Wang, Qingtao [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Malamud, Daniel [NYU College of Dentistry, 345 East 24th Street, New York, NY 10010 (United States); Deng, Haiteng, E-mail: dht@mail.tsinghua.edu.cn [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China)

    2013-04-24

    Highlights: ► A high-throughput method for profiling and quantification of the differentially expressed proteins in saliva samples was developed. ► Identified that DMBT1, S100A7, S100A8, S100A9 and alpha defensin were up-regulated in saliva from HIV-1 seropositive patients. ► Established analytical strategies are translatable to the clinical setting. -- Abstract: In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity.

  6. The association between urinary liver-type fatty acid-binding protein and chronic kidney disease classification in HIV-infected Japanese patients.

    Science.gov (United States)

    Hikasa, Shinichi; Yasuda, Megumi; Hideta, Kyoko; Kawakami, Mai; Higasa, Satoshi; Sawada, Akihiro; Tokugawa, Tazuko; Kimura, Takeshi

    2017-12-01

    Renal dysfunction is recognized with increasing frequency among the noninfectious comorbidities associated with human immunodeficiency virus (HIV) infection. Urinary liver-type fatty acid-binding protein (L-FABP) has been shown to be a new biomarker to screen for not only tubulointerstitial damage but also kidney dysfunction. We performed a cross-sectional study to determine the association between the urinary L-FABP and chronic kidney disease (CKD) among 77 HIV-infected Japanese patients by backward-stepwise multivariable logistic regression. The prevalence of individuals in the low risk was 80 %. Urinary L-FABP level was not associated with antiretroviral therapy and tenofovir disoproxil fumarate. On the other hand, urinary L-FABP level was independently associated with the CKD classification. Urinary L-FABP may be used as an adjunct to diagnose the CKD stage.

  7. Clinical research in HIV-1 infected children

    OpenAIRE

    Fraaij, Pieter

    2005-01-01

    textabstractAcquired immune deficiency syndrome (AIDS) was described for the first time in 1981. Two years later the previously unknown human immunodeficiency virus (HIV) was identified as the causative agent. HIV has been included in the genus Lent/viruses of the Retroviridae family. Two types are recognized: HIV-1 and HIV-2. Of these, HIV-1 is the primary etiologic agent of the current pandemic. HIV probably originates from simian immunodeficiency virus (SIV) which is endemic in African mon...

  8. HIV Type 1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels.

    Science.gov (United States)

    Eller, Michael A; Opollo, Marc S; Liu, Michelle; Redd, Andrew D; Eller, Leigh Anne; Kityo, Cissy; Kayiwa, Joshua; Laeyendecker, Oliver; Wawer, Maria J; Milazzo, Mark; Kiwanuka, Noah; Gray, Ronald H; Serwadda, David; Sewankambo, Nelson K; Quinn, Thomas C; Michael, Nelson L; Wabwire-Mangen, Fred; Sandberg, Johan K; Robb, Merlin L

    2015-05-15

    Untreated human immunodeficiency virus type 1 (HIV) infection is associated with persistent immune activation, which is an independent driver of disease progression in European and United States cohorts. In Uganda, HIV-1 subtypes A and D and recombinant AD viruses predominate and exhibit differential rates of disease progression. HIV-1 seroconverters (n = 156) from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow-up. The frequency of activated T cells was increased in HIV-1-infected Ugandans, compared with community matched uninfected individuals, but did not differ significantly between viral subtypes. Higher HIV-1 load, subtype D, older age, and high T-cell activation levels were associated with faster disease progression to AIDS or death. In a multivariate Cox regression analysis, HIV-1 load was the strongest predictor of progression, with subtype also contributing. T-cell activation did not emerge an independent predictor of disease progression from this particular cohort. These findings suggest that the independent contribution of T-cell activation on morbidity and mortality observed in European and North American cohorts may not be directly translated to the HIV epidemic in East Africa. In this setting, HIV-1 load appears to be the primary determinant of disease progression. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Parasite susceptibility to amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum.

    Science.gov (United States)

    Lachaud, Laurence; Bourgeois, Nathalie; Plourde, Marie; Leprohon, Philippe; Bastien, Patrick; Ouellette, Marc

    2009-01-15

    Visceral leishmaniasis (VL) is an opportunistic infection that can occur among patients infected with human immunodeficiency virus type 1 (HIV-1) in areas where both infections are endemic. Highly active antiretroviral therapy has decreased the incidence of VL in southern Europe among HIV-1-infected patients, but VL is still observed among patients with low CD4 cell counts, and most coinfected patients receiving highly active antiretroviral therapy experienced relapse, despite initial treatment with liposomal amphotericin B. Through long-term monitoring of VL in 10 patients with HIV-1 infection and/or AIDS, we compared parasite strains derived from primary and secondary episodes of VL. All the patients have received many courses of amphotericin B treatment and/or prophylaxis. Through molecular techniques, we have shown that secondary episodes of VL can be attributable to relapse (7 of 10 episodes) or reinfection (3 of 10). We developed an assay to measure amphotericin B susceptibility and found no evidence of decreased susceptibility among strains isolated from patients, some of whom were infected with the same isolate for up to 10 years. This apparent absence of resistance, as determined by in vitro susceptibility testing, has important consequences and suggests that amphotericin B will remain a useful drug of choice against VL, even after repetitive treatments or prophylactic use.

  10. Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of Elvitegravir-resistance HIV-1 integrase

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi [Shanghai Jiao Tong Univ., Shanghai (China). State Key Lab. of Microbial Metabolism and College of Life Science and Biotechnology; Cheng, Xiaolin [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Molecular Biophysics; Univ. of Tennessee, Knoxville, TN (United States). Dept. of Biochemistry and Cellular and Molecular Biology; Wei, Dongqing [Shanghai Jiao Tong Univ., Shanghai (China). State Key Lab. of Microbial Metabolism and College of Life Science and Biotechnology; Xu, Qin [Shanghai Jiao Tong Univ., Shanghai (China). State Key Lab. of Microbial Metabolism and College of Life Science and Biotechnology

    2014-11-06

    Although Elvitegravir (EVG) is a newly developed antiretrovirals drug to treat the acquired immunodeficiency syndrome (AIDS), drug resistance has already been found in clinic, such as E92Q/N155H and Q148H/G140S. Several structural investigations have already been reported to reveal the molecular mechanism of the drug resistance. As full length crystal structure for HIV-1 integrase is still unsolved, we use in this paper the crystal structure of the full length prototype foamy virus (PFV) in complex with virus DNA and inhibitor Elvitegravir as a template to construct the wild type and E92Q/N155H mutant system of HIV-1 integrase. Molecular dynamic simulations was used to revel the binding mode and the drug resistance of the EVG ligand in E92Q/N155H. Several important interactions were discovered between the mutated residues and the residues in the active site of the E92Q/N155H double mutant pattern, and cross correlation and clustering methods were used for detailed analysis. The results from the MD simulation studies will be used to guide the experimental efforts of developing novel inhibitors against drug-resistant HIV integrase mutants.

  11. Seventeen-year-old mother-to-child HIV type 1 transmission identified by phylogeny and signature patterns

    DEFF Research Database (Denmark)

    Katzenstein, T.L.; Petersen, A.B.; Jorgensen, L.B.

    2008-01-01

    A case, in which the clinical suspicion of perinatal HIV transmission of a newly diagnosed 17-year-old woman was supported by the phylogenetic analyses of pol sequences obtained for routine resistance testing and further substantiated by analyses of gag and env, is described Udgivelsesdato: 2008/8...

  12. Characterization of near full-length genomes of HIV type 1 strains in Denmark: Basis for a universal therapeutic vaccine

    DEFF Research Database (Denmark)

    Andresen, Betina S.; Vinner, Lasse; Tang, Sheila Tuyet

    2007-01-01

    We report here the near full-length sequence characterization of 17 Danish clinical HIV-1 strains isolated from HLA-A02 patients not in need of ART, with relatively low viral loads and normal CD4 cell counts. Sequencing was performed directly on DNA extracted from short-term cocultures of PBMCs. ...

  13. Comparison of commercial kits for the detection of antibody to human immunodeficiency virus type 1 (HIV-1) in Nigeria.

    Science.gov (United States)

    Chikwem, J O; Mohammed, I; Ola, T O

    1990-03-01

    Four commercial kits for the detection of antibodies to HIV-1 were compared with regard to their sensitivity, specificity and positive predictive value. The Wellcozyme competitive enzyme immunoassay was the least sensitive (62.5%), while Roche EIA, was the most sensitive (100%). All the commercial kits gave false negative results except the Roche EIA system. The Serodia particle agglutination test had the least positive predictive value of 26.9% while Roche EIA had the highest (88.9%). Our results show that commercial HIV-I antibody test kits are not equally sensitive in detecting positive sera. The practice of using Wellcozyme EIA alone for screening blood meant for transfusion should be discouraged because it does not detect all positive sera and might therefore increase the chances of transfusing HIV-I positive blood. The Roche EIA system appears to be the most reliable for screening blood. Test systems which detect HIV-2 should also be used for screening blood meant for transfusion.

  14. Potent cross-reactive immune response against the wild-type and drug-resistant forms of HIV reverse transcriptase after the chimeric gene immunization.

    Science.gov (United States)

    Starodubova, Elizaveta; Boberg, Andreas; Ivanov, Alexander; Latyshev, Oleg; Petrakova, Natalia; Kuzmenko, Yulia; Litvina, Marina; Chernousov, Alexander; Kochetkov, Sergey; Karpov, Vadim; Wahren, Britta; Isaguliants, Maria G

    2010-02-23

    HIV reverse transcriptase (RT) can be considered as a target and an instrument of immunotherapy aimed at limiting the emergence and spread of drug-resistant HIV. The chimeric genes coding for the wild-type and multi-drug-resistant RT (RT1.14) fused to lysosome-associated membrane protein 1 (LAMP-1) were injected intramuscularly into BALB/c mice. The immune response was assessed by ELISpot, cytokine ELISA intracellular IFN-gamma staining, and antibody ELISA. The genes for RT- and RT1.14-LAMP fusions (RT-LAMP and RT1.14-LAMP) were immunogenic generating a mixed Th1/Th2-profile of immune response, while the wild-type RT gene induced only weak immune response. Specific secretion of Th1-cytokines increased with increasing level of RT modification: RTtype variants. Gene immunization induced specific IgG (10(3)), and transient serum IgA (10(2)). Low immunogenicity of the parental RT may be explained by tolerance to the enzyme that is a common endogenous retroviral antigen. Potent immune recognition of RT after immunization with chimeric RT genes indicates that this tolerance could be overcome. Immunization with mutant HIV genes may represent an immunotherapeutical supplement to antiretroviral treatment preventing the emergence of drug resistance. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Thermal stability of the human immunodeficiency virus type 1 (HIV-1 receptors, CD4 and CXCR4, reconstituted in proteoliposomes.

    Directory of Open Access Journals (Sweden)

    Mikhail A Zhukovsky

    2010-10-01

    Full Text Available The entry of human immunodeficiency virus (HIV-1 into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4.We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E(a of 269 kJ/mol (64.3 kcal/mol and an inactivation temperature (T(i of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E(a of 278 kJ/mol (66.5 kcal/mol, and a T(i of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules.Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors.

  17. Psychoneuroimmunology and HIV-1.

    Science.gov (United States)

    Antoni, Michael H.; And Others

    1990-01-01

    Presents evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high risk human immunodeficiency virus-Type 1 (HIV-1) seronegative and very early stage seropositive homosexual men. HIV-1 infection is cast as chronic disease for which early…

  18. HIV and AIDS

    Science.gov (United States)

    ... one of the most serious, deadly diseases in human history. HIV causes a condition called acquired immunodeficiency syndrome — better known as AIDS . HIV destroys a type of defense cell in the body called a CD4 helper lymphocyte (pronounced: LIM-foe- ...

  19. Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(' in China.

    Directory of Open Access Journals (Sweden)

    Hanping Li

    Full Text Available OBJECTIVE: Mutations associated with HIV drug resistance have been extensively characterized at the HIV-1 polymerase domain, but more studies have verified that mutations outside of the polymerase domain also results in resistance to antiviral drugs. In this study, mutations were identified in 354 patients experiencing antiretroviral therapy (ART failure and in 97 naïve-therapy patients. Mutations whose impact on antiviral drugs was unknown were verified by phenotypic testing. METHODS: Pol sequences of HIV subtype B(' obtained from patients experiencing ART failure and from naïve-therapy patients were analyzed for mutations distinct between two groups. Mutations that occurred at a significantly higher frequency in the ART failure than the naïve-therapy group were submitted to the Stanford HIV Drug Resistance Database (SHDB to analyze the correlation between HIV mutations and drug resistance. For mutations whose impact on the antiviral drug response is unknown, the site-directed mutagenesis approach was applied to construct plasmids containing the screened mutations. 50% inhibitory concentration (IC(50 to AZT, EFV and NVP was measured to determine the response of the genetically constructed viruses to antiviral drugs. RESULTS: 7 mutations at 6 positions of the RT region, D123E, V292I, K366R, T369A, T369V, A371V and I375V, occurred more frequently in the ART failure group than the naïve-therapy group. Phenotypic characterization of these HIV mutants revealed that constructed viruses with mutations A371V and T369V exhibited dual resistance to AZT and EFV respectively, whereas the other 5 mutations showed weak resistance. Although the impact of the other six mutations on response to NVP was minimal, mutation T369V could enhance resistance to NVP. CONCLUSIONS: This study demonstrated that mutations at the RT C-terminal in subtype B' could result in resistance to RT inhibitors if the mutations occurred alone, but that some mutations could promote

  20. Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress

    Science.gov (United States)

    Garg, Abhishek D; Maes, Hannelore; van Vliet, Alexander R; Agostinis, Patrizia

    2015-01-01

    The endoplasmic reticulum (ER) is at the center of a number of vital cellular processes such as cell growth, death, and differentiation, crosstalk with immune or stromal cells, and maintenance of proteostasis or homeostasis, and ER functions have implications for various pathologies including cancer. Recently, a number of major hallmarks of cancer have been delineated that are expected to facilitate the development of anticancer therapies. However, therapeutic induction of ER stress as a strategy to broadly target multiple hallmarks of cancer has been seldom discussed despite the fact that several primary or secondary ER stress-inducing therapies have been found to exhibit positive clinical activity in cancer patients. In the present review we provide a brief historical overview of the major discoveries and milestones in the field of ER stress biology with important implications for anticancer therapy. Furthermore, we comprehensively discuss possible strategies enabling the targeting of multiple hallmarks of cancer with therapy-induced ER stress. PMID:27308392

  1. Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis From HPV Infection to Cervical Cancer.

    Science.gov (United States)

    Clifford, Gary M; Tully, Stephen; Franceschi, Silvia

    2017-05-01

    Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population. A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11739 with normal cytological findings; 1784 with atypical squamous cells of undetermined significance (ASCUS); 2173 with low-grade and 1282 with high-grade squamous intraepithelial lesions (HSILs) diagnosed cytologically; 1198 with cervical intraepithelial neoplasia grade 1 (CIN1), 456 with CIN2, and 455 with CIN3 diagnosed histologically; and 796 with invasive cervical cancers (ICCs). A large proportion of WHIV, and almost all with ICCs, were from Africa. In Africa, HPV 16 accounted for 13% of HPV-positive WHIV with normal cytological findings, but this proportion increased through ASCUS, low-grade squamous intraepithelial lesions, CIN1, and CIN2 (18%-25%), up to 41%-47% for CIN3 and ICCs. Only HPV 16, HPV 18, and HPV 45 accounted for a greater proportion of HPV infections in ICCs compared with normal cytological findings (ICC:normal ratios, 3.68, 2.47, and 2.55, respectively). Other high-risk types accounted for important proportions of low- and/or high-grade lesions, but their contribution dropped in ICCs, with ICC:normal ratios in Africa ranging from 0.79 for HPV 33 down to 0.38 for HPV 56. Findings for HPV 16 and HPV 18 in Europe/North America, Asia, and Latin America were compatible with those from Africa. HPV 16 and HPV 18 in particular, but also HPV 45, at least in Africa, warrant special attention in WHIV. Broad consistency of findings with those in HIV-uninfected population would suggest that the risk stratification offered by partial HPV genotyping tests also have relevance for HIV-positive women.

  2. Drug susceptibility to etravirine and darunavir among Human Immunodeficiency Virus Type 1-derived pseudoviruses in treatment-experienced patients with HIV/AIDS in South Korea.

    Science.gov (United States)

    Kwon, Oh-Kyung; Kim, Sung Soon; Rhee, Jee Eun; Kee, Mee-Kyung; Park, Mina; Oh, Hye-Ri; Choi, Ju-Yeon

    2015-04-09

    In South Korea, about 20 types of antiretroviral drugs are used in the treatment of patients with human immunodeficiency virus/acquired immune deficiency syndrome. Since 2010, raltegravir, etravirine, and darunavir have been spotlighted as new drugs for highly active antiretroviral therapy (HAART)-experienced adults with resistant HIV-1 in South Korea. In this study, we investigated potential susceptibility of pseudoviruses derived from treatment-experienced Korean patients to etravirine vs efavirenz and to darunavir vs amprenavir and indinavir using a modified single-round assay. Pseudoviruses derived from nine treatment-experienced patients infected with HIV-1 were investigated by comparison with the wild-type strain pNL4-3. The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared. The intensity of genotypic drug resistance was classified based on the 'SIR' interpretation of the Stanford data base. Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients. Pseudoviruses derived from patients KRB4025 and KRB8014, who exhibited long-term use of protease inhibitors, showed an outside of tested drug concentration, especially for amprenavir and indinavir. However, they exhibited a lower fold-change in resistance to darunavir. Etravirine and darunavir have been used in HAART since 2010 in South Korea. Therefore, these antiretroviral drugs together with other newly introduced antiretroviral drugs are interesting for the optimal treatment of patients with treatment failure. This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

  3. International Patterns of Practice in the Management of Radiation Therapy-induced Nausea and Vomiting

    Energy Technology Data Exchange (ETDEWEB)

    Dennis, Kristopher; Zhang Liying [Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Lutz, Stephen [Blanchard Valley Health Systems, Findlay, Ohio (United States); Baardwijk, Angela van [Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Linden, Yvette van der [Leiden University Medical Center, Leiden (Netherlands); Holt, Tanya [Radiation Oncology Mater Centre, Princess Alexandra Hospital, Brisbane (Australia); Arnalot, Palmira Foro [Parc de Salut Mar. Universitat Pompeu Fabra Barcelona (Spain); Lagrange, Jean-Leon [AP-HP Hopital Henri-Mondor, Universite Paris Est Creteil, Creteil (France); Maranzano, Ernesto [' S. Maria' Hospital, Terni (Italy); Liu, Rico [Queen Mary Hospital, Hong Kong (China); Wong, Kam-Hung [Queen Elizabeth Hospital, Hong Kong (Hong Kong); Wong, Lea-Choung [National University Cancer Institute (Singapore); Vassiliou, Vassilios [Bank of Cyprus Oncology Centre, Nicosia (Cyprus); Corn, Benjamin W. [Tel Aviv Medical Center, Tel Aviv (Israel); De Angelis, Carlo; Holden, Lori; Wong, C. Shun [Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2012-09-01

    Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT){sub 3} receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk

  4. Sexual risk behaviors by relationship type and trauma history among HIV-positive men who have sex with men.

    Science.gov (United States)

    Kamen, Charles; Etter, Darryl; Flores, Sergio; Sharp, Susan; Lee, Susanne; Gore-Felton, Cheryl

    2013-02-01

    The association of trauma exposure and coping style to sexual risk behavior has yet to be fully examined in the context of primary and casual sexual partnerships. The current study assessed a high risk sexual behavior-unprotected anal intercourse (UAI)-in a high risk population of HIV-positive men who have sex with men (MSM) with a history of trauma. Using audio computer-assisted self-interview technology, 132 HIV-positive MSM completed measures of trauma exposure, trauma symptoms, coping strategies, and sexual risk behavior. Hierarchical logistic regression analyses indicated that completing more years of education and having experienced sexual abuse were positively associated with UAI with casual partners. Additionally, use of active coping was negatively associated with UAI with casual partners and the final model significantly predicted variance in UAI with casual partners. However, no variables were significantly associated with UAI with primary partners, suggesting that sexual risk behavior with primary partners may be associated with factors not commonly assessed in risk prediction or prevention research. We discuss the results in the context of developing new or modifying existing interventions to address rates of sexual risk in the relationships of HIV-positive MSM.

  5. 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, ...

  6. 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 ...

  7. Nadir CD4+, religion, antiretroviral therapy, incidence of type 2 diabetes mellitus, and increasing rates of obesity among black Africans with HIV disease

    Directory of Open Access Journals (Sweden)

    Mbungu Fuele S

    2012-11-01

    Full Text Available Madone Mandina Ndona,1 Benjamin Longo-Mbenza,2 Roger Wumba,3 Barthelemy Tandu Umba,4 Baudouin Buassa-bu-Tsumbu,5 Marcel Mbula Mambimbi,1 Thaddée Odio Wobin,1 Simon Mbungu Fuele61Department of Internal Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo; 2Walter Sisulu University, Faculty of Health Sciences, Mthatha, Eastern Cape, South Africa; 3Tropical Medicine Department, Infectious and Parasitic Diseases, University Clinic of Kinshasa and University of Kinshasa, Kinshasa, Democratic Republic of Congo; 4Department of Gynecology, 5Department of Biochemistry, University of Kinshasa, Kinshasa, Democratic Republic of Congo; 6Biostatistics Unit of Lomo Medical Center and Heart of Africa Center of Cardiology, Kinshasa, Democratic Republic of CongoBackground: The purpose of this study was to determine the cross-sectional association between some sociodemographic factors and antiretroviral therapy (ART, as well as the incidence and predictors of type 2 diabetes mellitus among Central Africans with human immunodeficiency virus (HIV disease.Methods: This study had a cross-sectional design and was a prospective analysis of 102 patients with HIV disease (49 on ART versus 53 not on ART in Kinshasa, Democratic Republic of Congo, between 2004 and 2008. A Cox regression model was used to assess for any relationship between type 2 diabetes and exposure to combination ART without protease inhibitors, after adjusting for known risk factors for type 2 diabetes, nadir CD4 and CD8 levels, viral load, marital status, and religion.Results: Unexpectedly elevated rates of smoking, excess alcohol intake, and ART-related total, abdominal, and peripheral obesity were observed in our study group of HIV patients. At the end of follow-up, five patients were diagnosed with type 2 diabetes (incidence rate 4.9%, 9.8 per 1000 person-years. Univariate risk factors for type 2 diabetes were male gender (relative risk [RR] 1.1, 95% confidence interval [CI] 1

  8. Performance of 3 Rapid Tests for Discrimination Between HIV-1 and HIV-2 in Guinea-Bissau, West Africa

    DEFF Research Database (Denmark)

    Hønge, Bo Langhoff; Bjarnason Obinah, Magnús Pétur; Jespersen, Sanne

    2014-01-01

    As HIV-2 is intrinsically resistant to nonnucleoside reverse transcriptase inhibitors, it is mandatory to discriminate between HIV types before initiating antiretroviral treatment. Guinea-Bissau has the world's highest prevalence of HIV-2 and HIV-1/HIV-2 dually infected individuals. We evaluated ...

  9. Introducing Catastrophe-QSAR. Application on Modeling Molecular Mechanisms of Pyridinone Derivative-Type HIV Non-Nucleoside Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    Marius Lazea

    2011-12-01

    Full Text Available The classical method of quantitative structure-activity relationships (QSAR is enriched using non-linear models, as Thom’s polynomials allow either uni- or bi-variate structural parameters. In this context, catastrophe QSAR algorithms are applied to the anti-HIV-1 activity of pyridinone derivatives. This requires calculation of the so-called relative statistical power and of its minimum principle in various QSAR models. A new index, known as a statistical relative power, is constructed as an Euclidian measure for the combined ratio of the Pearson correlation to algebraic correlation, with normalized t-Student and the Fisher tests. First and second order inter-model paths are considered for mono-variate catastrophes, whereas for bi-variate catastrophes the direct minimum path is provided, allowing the QSAR models to be tested for predictive purposes. At this stage, the max-to-min hierarchies of the tested models allow the interaction mechanism to be identified using structural parameter succession and the typical catastrophes involved. Minimized differences between these catastrophe models in the common structurally influential domains that span both the trial and tested compounds identify the “optimal molecular structural domains” and the molecules with the best output with respect to the modeled activity, which in this case is human immunodeficiency virus type 1 HIV-1 inhibition. The best molecules are characterized by hydrophobic interactions with the HIV-1 p66 subunit protein, and they concur with those identified in other 3D-QSAR analyses. Moreover, the importance of aromatic ring stacking interactions for increasing the binding affinity of the inhibitor-reverse transcriptase ligand-substrate complex is highlighted.

  10. Human immunodeficiency type-1 virus (HIV-1) infection in serodiscordant couples (SDCs) does not have an impact on embryo quality or intracytoplasmic sperm injection (ICSI) outcome.

    Science.gov (United States)

    Melo, Marco Antonio Barreto; Meseguer, Marcos; Bellver, José; Remohí, José; Pellicer, Antonio; Garrido, Nicolás

    2008-01-01

    To evaluate the embryo quality in our program for human immunodeficiency type-1 virus (HIV-1) serodiscordant couples (SDCs) with the male infected in comparison with a tubal-factor infertility control group. Retrospective case-control study. Instituto Valenciano de Infertilidad, Valencia, Spain. Thirty SDC and 79 control couples without HIV-1 infection attending for intracytoplasmic sperm injection (ICSI). Only first cycles were considered. Controlled ovarian hyperstimulation and ICSI in both groups; sperm wash, nested polymerase chain reaction (PCR) in semen sample, and capacitation by swim-up after thawing the semen sample in the SDC group; and sperm capacitation by swim-up after thawing the semen sample in the control group. ICSI procedure and embryo characteristics (fertilization, cleavage, embryo morphology, and development) and cycle outcome (ongoing pregnancy and miscarriage rates). Fertilization and cleavage rates were similar between the groups. On days 2 and 3 of embryo development, very similar embryo features were found between the groups. There was no difference in mean number of optimal embryos on day 3. When embryos were cultured up to 5-6 days, a significant increase in embryo blockage was found in the SDC group compared with the control group. The mean number of optimal blastocysts on day 6 was comparable in both groups. No difference was found regarding the number of cryopreserved and transferred embryos or implantation, pregnancy, multiple pregnancy, or miscarriage rates between the groups. HIV-1 infection in SDCs with infected males does not appear to have a significantly negative impact on embryo development or ICSI outcome.

  11. Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: effects on nucleoside analog resistance.

    Science.gov (United States)

    Song, Q; Yang, G; Goff, S P; Prasad, V R

    1992-12-01

    A Glu-89-->Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, or Lys displayed only moderate or no resistance. A similar result was obtained with inhibition by PFA, except that the Asp-89 mutant also displayed resistance. Furthermore, the introduction of Glu-89-->Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA.

  12. Comparison of Parasitological, Serological, and Molecular Tests for Visceral Leishmaniasis in HIV-Infected Patients: A Cross-Sectional Delayed-Type Study

    Science.gov (United States)

    Cota, Gláucia Fernandes; de Sousa, Marcos Roberto; de Freitas Nogueira, Betânia Mara; Gomes, Luciana Inácia; Oliveira, Edward; Assis, Tália Santana Machado; de Mendonça, Andréa Laender Pessoa; Pinto, Bruna Fernandes; Saliba, Juliana Wilke; Rabello, Ana

    2013-01-01

    The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnosis of visceral leishmaniasis (VL) in a large series of human immunodeficiency virus (HIV)-infected patients. In this delayed-type cross-sectional study, 113 HIV-infected symptomatic patients were evaluated by an adjudication committee after clinical follow-up to establish the presence or absence of VL as the target condition (reference test). The index tests were recombinant K39 antigen-based immunochromatographic test (rK39), indirect fluorescent antibody test (IFAT), prototype kit of direct agglutination test (DAT-LPC), and real-time polymerase chain reaction (qPCR) in peripheral blood. Compared with parasitological test and adjudication committee diagnosis or latent class model analyses, IFAT and rk39 dipstick test presented the lowest sensitivity. DAT-LPC exhibited good overall performance, and there was no statistical difference between DAT-LPC and qPCR diagnosis accuracy. Real-time PCR emerges as a less invasive alternative to parasitological examination for confirmation of cases not identified by DAT. PMID:23836568

  13. Enrichment of HLA Types and Single-Nucleotide Polymorphism Associated With Non-progression in a Strictly Defined Cohort of HIV-1 Controllers

    Directory of Open Access Journals (Sweden)

    Samantha J. Westrop

    2017-06-01

    Full Text Available HIV-1 controllers (HIC are extremely rare patients with the ability to control viral replication, maintain unchanging CD4 T-cell count, and evade disease progression for extensive periods of time, in the absence of antiretroviral therapy. In order to establish the representation of key genetic correlates of atypical disease progression within a cohort of HIV-1+ individuals who control viral replication, we examine four-digit resolution HLA type and single-nucleotide polymorphisms (SNP previously identified to be correlated to non-progressive infection, in strictly defined HIC. Clinical histories were examined to identify patients exhibiting HIC status. Genomic DNA was extracted, and high definition HLA typing and genome-wide SNP analysis was performed. Data were compared with frequencies of SNP in European long-term non-progressors (LTNP and primary infection cohorts. HLA-B alleles associated with atypical disease progression were at very high frequencies in the group of five HIC studied. All four HIC of European ancestry were HLA-B*57+ and half were also HLA-B*27+. All HIC, including one of self-reported African ethnicity, had the HLA-Cw*0602 allele, and the HLA-DQ9 allele was present only in HIC of European ancestry. A median 95% of the top 19 SNP known to be associated with LTNP status was observed in European HIC (range 78–100%; 17/19 of the SNP considered mapped to chromosome 6 in the HLA region, whereas 2/19 mapped to chromosome 8. The HIC investigated here demonstrated high enrichment of HLA types and SNP previously associated with long-term non-progression. These findings suggest that the extreme non-progressive phenotype considered here is associated with a genetic signature characterized by a single-genetic unit centered around the HLA-B*57 haplotype and the possible additive effect of HLA-B*27.

  14. Active replication of hepatitis B virus (HBV in HIV type 1 and in HIV type 2 infected patients Replicação ativa do vírus da hepatite B (HBV em doentes infectados pelo vírus da imunodeficiência humana (HIV de tipo 1 ou de tipo 2

    Directory of Open Access Journals (Sweden)

    M.F. Barros

    1996-08-01

    Full Text Available To evaluate the effect of concurrent infection by HIV on HBV infection or immunity, we have studied a group of 66 HIV1+ symptomatic Caucasian patients and another of 38 African HIV2+ asymptomatic individuals, concerning their HBV status: serological markers of infection and presence of HBV-DNA in serum, the last taken as sign of hepatitis B virus active replication, were monitored. HIV+ groups were compared with seronegative controls, adequately matched for age, sex and ethnological background. HBV DNA was found in 7.6% of HIV1+ Caucasian patients and 3.2% of seronegative controls; in African HIV2+ individuals 2.6% were also HBV DNA+, a percentage close to that found in HIV2 seronegative controls (2.9%. No correlation was found between HIV infection and HBV active replication. Immunodepression that follows HIV infection over time may be compatible with a degree of T cell function capable of avoiding reinfection with or reactivation of HBV, even in symptomatic stages of acquired immunodeficiency syndrome. Our findings are relevant to the choice of preventive strategies in populations at risk for HIV and HBV infection.A fim de avaliar as conseqüências da infecção por HIV no curso da infecção por HBV, ou na imunidade anteriormente adquirida, estudamos um grupo de 66 doentes Caucasóides HIV1+ sintomáticos e outro de 38 indivíduos seropositivos para HIV2 e provenientes da África, quanto a marcadores serológicos de infecção por HBV e quanto à presença de DNA viral circulante, tomada como sinal de replicação ativa do vírus da hepatite. Os grupos HIV+ foram comparados com controles seronegativos adequados tendo-se verificado que 7.6% dos doentes HIV1+ eram também HBV-DNA+ (versus 3.2% nos seronegativos bem como 2.6% dos HIV2+ (versus 2.9% nos controles seronegativos, não sendo as diferenças estatisticamente significativas em qualquer um dos casos e não tendo sido encontrada correlação entre infecção por HIV e replicação ativa

  15. Evaluation of screening kits for the detection of anti-human immunodeficiency virus type 1 and 2 (HIV-1/2) antibodies.

    Science.gov (United States)

    Chin, L T; Yang, B S; Chen, J W; Yang, C M; Chou, C C; Li, L; Hung, C M; Tsai, S J; Lin, K S

    1995-08-01

    HIV-1/HIV-2 3rd generation (Abbott), Wellcozyme HIV 1 + 2 (Murex), Enzygnost Anti-HIV 1/-HIV 2 (Behring), and Genelavia Mixt (Sanofi Diagnostics Pasteur) are currently registered by authorities as enzyme immunoassays (EIAs) for detecting HIV-1/2 infection. The present study dissects these reagents by means of the major antigenic components, assay principles and their actual performance. The performances have been evaluated by their test results in international panels of seroconversion, mixed titer performance and HIV-1/2 combination, respectively. Those EIA tests were further used to examine 26 potentially false-reacting samples, serial diluted sera prepared from two confirmed positive specimens and 720 specimens obtained from random blood donors in the Taipei Blood Center, Chinese Blood Services Foundation (CBSF). The results showed that, although standard sera of the mixed titer, performance and HIV-1/2 combination rows could not distinguish significantly among various EIAs, the seroconverting samples clearly showed their differences. The differences, as calculated by using 3 of 4 seroconverting sera, was a backward window period ranging from 19 to 23 days as compared to the detection of HIV-1 antigens. Together, these studies strongly suggest that assays which are capable of detecting HIV-specific IgM and IgG antibodies have a shorter seroconversion window. Furthermore, the HIV-2 antigen seems to be crucial for successful detection of anti-HIV-2. Finally, testing anti-HIV-1/2 in the routine screenings is expected not to increase the exclusion rate of blood units currently acquired from the examination of anti-HIV-1. Consequently, with both HIV-1/2 specificities and the ability of early detection, IgM/IgG-captured EIAs may represent a better screening method than assays based solely on the detection of HIV-specific IgG.

  16. Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: effects on nucleoside analog resistance.

    OpenAIRE

    Song, Q; Yang, G; Goff, S P; Prasad, V R

    1992-01-01

    A Glu-89-->Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, ...

  17. Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells

    Science.gov (United States)

    Chan, Tze-Sian; Pai, Vincent C.; Tan, Kok-Tong; Yen, Chia-Jui; Hsu, Shu-Ching; Chen, Wei-Yu; Shan, Yan-Shen; Lee, Michael T.; Chu, Jui-Mei

    2016-01-01

    Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy–treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif–positive (ELR+) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR+ chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy. PMID:27881732

  18. Bloodborne transmission of Hiv/Aids in Africa: Challenges and ...

    African Journals Online (AJOL)

    The causative agent of Acquired Immune Deficiency Syndrome (AIDS), is the human immuno-deficiency virus(HIV). Two types of HIV( types 1 and 2), have been linked with AIDS. HIV-2, has been described mainly in West Africa. HIV can be transmitted both in cellular and plasma components of blood. Bloodborne ...

  19. Enzymatic properties and sensitivity to inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with Glu-138-->Arg and Tyr-188-->His mutations.

    Science.gov (United States)

    Zhang, H; Vrang, L; Bäckbro, K; Unge, T; Noréen, R; Oberg, B

    1994-05-01

    Two mutants of HIV-1 reverse transcriptase (RT), Tyr-188-->His and Glu-138-->Arg have been prepared and their catalytic properties and sensitivities to inhibitors studied. As compared to wild type RT, a reduction in catalytic efficiency and turn over number was observed, especially for the Tyr-188-->His mutant. The non-nucleoside inhibitors nevirapine, L-697,661 and 9-Cl-TIBO caused a mixed type of inhibition of RT (Arg-138) with respect to substrate, and with the exception of a non-competitive inhibition by nevirapine, also a mixed type of inhibition of RT (His-188). Foscarnet (PFA) caused a non-competitive type of inhibition of RT (Arg-138) and a mixed inhibition of RT (His-188). The inhibition by ddG-TP was competitive with both mutant RTs. Inhibition by nevirapine gave IC50 values of 0.15, 0.23 and 0.72 microM; by 9-Cl-TIBO of 0.20, 2.50 and 10.3 microM; by L-697,661 of 0.064, 0.28 and 0.60 microM; by ddGTP of 0.13, 0.14 and 0.02 microM; by PFA of 17.0, 48.0 and 15.0 microM for RT wt, RT (Arg-138) and RT (His-188), respectively.

  20. Possible allosteric interactions of monoindazole-substituted P2 cyclic urea analogues with wild-type and mutant HIV-1 protease

    Science.gov (United States)

    Garg, Rajni; Bhhatarai, Barun

    2008-10-01

    Our ongoing efforts to understand the difference in the binding pattern of HIV-1 protease inhibitor (HIVPI) with the wild-type and mutant HIV-1 protease (HIVPR) and to provide mechanistic insight are continued further. We report here the results of a recent quantitative structure-activity relationship (QSAR) study on monoindazole-substituted P2 analogues of cyclic urea HIVPIs. The QSAR models revealed an inverted parabolic relationship between biological activity and calculated molar refractivity (CMR). That is, biological activity first decreases with increase in CMR and at a certain minimum point (inversion point) it suddenly changes and increases with further increase in CMR. CMR is a measure of volume-dependent-polarizability and is an indication of the polar interactions between ligand and receptor. The results seem to be best rationalized by larger molecules inducing a change in a receptor unit that allows for a new mode of interaction. Similar QSAR models were also observed for the biological activity of these molecules tested against a panel of mutant viruses including mutant strains with single amino acid substitution (I84V), double amino acid substitutions (I84V/V82F), and multiple amino acid changes corresponding to mutations observed in clinical isolates of patients treated with Ritonavir®. Interestingly the inversion points for these mutant strains were found larger than for wild-type. The subtle but significant difference in the inversion point indicates change in the shape and size of the binding pocket. Earlier QSAR studies have shown that the correlation of biological activity with an inverted parabola is an indicative of the `allosteric interaction' of the ligands with the receptor. This report presents a detail analysis of these observations.

  1. Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

    Science.gov (United States)

    Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

    2016-03-01

    The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding. © The Author(s) 2015.

  2. Worldwide molecular epidemiology of HIV

    Directory of Open Access Journals (Sweden)

    Henry I Z Requejo

    2006-04-01

    Full Text Available Human immunodeficiency virus (HIV is the worldwide disseminated causative agent of acquired immunodeficiency syndrome (AIDS. HIV is a member of the Lentivirus genus of Retroviridae family and is grouped in two types named HIV-1 and HIV-2. These viruses have a notable ability to mutate and adapt to the new conditions of human environment. A large incidence of errors at the transcriptional level results in changes on the genetic bases during the reproductive cycle. The elevated genomic variability of HIV has carried important implications for the diagnosis, treatment and prevention as well as epidemiologic investigations. The present review describes important definitions and geographical distribution of subtypes, circulating recombinant forms and other genomic variations of HIV. The present study aimed at leading students of Biomedical Sciences and public health laboratory staff guidance to general and specific knowledge about the genomic variability of the HIV.

  3. The preparation and characterization of biological isolates of HIV-1

    OpenAIRE

    2012-01-01

    M.Sc. It is the widely accepted view that the human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS) and that South Africa harbors mainly HIV type 1 subtype C (HIV-1 C). Extensively characterized biological isolates (especially of HIV-1 subtype C) for use in HIV/AIDS vaccine and drug development are not readily available. This study evaluated three different protocols for the expansion of virus from infected PBMC's of 68 HIV/AIDS patients (de...

  4. Astrocytes as an HIV Reservoir: Mechanism of HIV Infection.

    Science.gov (United States)

    Li, Guan-Han; Henderson, Lisa; Nath, Avindra

    2016-01-01

    If we have any hope of achieving a cure for HIV infection, close attention to the cell types capable of getting infected with HIV is necessary. Of these cell types, astrocytes are the most ideal cell type for the formation of such a reservoir. These are long-lived cells with a very low turnover rate and are found in the brain and the gastrointestinal tract. Although astrocytes are evidently resistant to infection of cell-free HIV in vitro, these cells are efficiently infected via cell-tocell contact by which immature HIV virions bud off lymphocytes and have the ability to directly bind to CXCR4, triggering the process of fusion in the absence of CD4. In this review, we closely examine the evidence for HIV infection of astrocytes in the brain and the mechanisms for viral entry and regulation in this cell type, and discuss an approach for controlling this viral reservoir.

  5. Connecting the Dots: Therapy-Induced Senescence and a Tumor-Suppressive Immune Microenvironment.

    Science.gov (United States)

    Vilgelm, Anna E; Johnson, C Andrew; Prasad, Nripesh; Yang, Jinming; Chen, Sheau-Chiann; Ayers, Gregory D; Pawlikowski, Jeff S; Raman, Dayanidhi; Sosman, Jeffrey A; Kelley, Mark; Ecsedy, Jeffrey A; Shyr, Yu; Levy, Shawn E; Richmond, Ann

    2016-06-01

    Tumor cell senescence is a common outcome of anticancer therapy. Here we investigated how therapy-induced senescence (TIS) affects tumor-infiltrating leukocytes (TILs) and the efficacy of immunotherapy in melanoma. Tumor senescence was induced by AURKA or CDK4/6 inhibitors (AURKAi, CDK4/6i). Transcriptomes of six mouse tumors with differential response to AURKAi were analyzed by RNA sequencing, and TILs were characterized by flow cytometry. Chemokine RNA and protein expression were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Therapeutic response was queried in immunodeficient mice, in mice with CCL5-deficient tumors, and in mice cotreated with CD137 agonist to activate TILs. CCL5 expression in reference to TIS and markers of TILs was studied in human melanoma tumors using patient-derived xenografts (n = 3 patients, n = 3 mice each), in AURKAi clinical trial samples (n = 3 patients, before/after therapy), and in The Cancer Genome Atlas (n = 278). All statistical tests were two-sided. AURKAi response was associated with induction of the immune transcriptome (P = 3.5 x 10-29) while resistance inversely correlated with TIL numbers (Spearman r = -0.87, P tumors regressed, P = .01) and in mice bearing CCL5-deficient vs control tumors (P = .61 vs P = .02); however, AURKAi response was greatly enhanced in mice also receiving T-cell-activating immunotherapy (P tumors, CCL5 expression was also induced by AURKAi (P ≤ .02) and CDK4/6i (P = .01) and was associated with increased immune marker expression (P = 1.40 x 10-93). Senescent melanoma cells secret CCL5, which promotes recruitment of TILs. Combining TIS with immunotherapy that enhances tumor cell killing by TILs is a promising novel approach to improve melanoma outcomes. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. 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 ...

  7. 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 ...

  8. 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: ...

  9. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates

    Science.gov (United States)

    García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L.; Seaman, Michael S.; Montefiori, David C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Self, Steven G.; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Lee, Carter; Kibler, Karen V.; Jacobs, Bertram L.; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe

    2017-01-01

    ABSTRACT The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4+ and CD8+ T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4+ and CD8+ T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4+ and CD8+ T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions. IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1

  10. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.

    Science.gov (United States)

    García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L; Seaman, Michael S; Montefiori, David C; Yates, Nicole L; Tomaras, Georgia D; Ferrari, Guido; Foulds, Kathryn E; Roederer, Mario; Self, Steven G; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W; Burke, Brian; Cristillo, Anthony D; Weiss, Deborah E; Lee, Carter; Kibler, Karen V; Jacobs, Bertram L; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe; Esteban, Mariano

    2017-05-01

    The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4+ and CD8+ T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4+ and CD8+ T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4+ and CD8+ T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions.IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1 protection

  11. HIV type 1 subtype A envelope genetic evolution in a slow progressing individual with consistent broadly neutralizing antibodies.

    Science.gov (United States)

    Dieltjens, Tessa; Loots, Nathalie; Vereecken, Katleen; Grupping, Katrijn; Heyndrickx, Leo; Bottieau, Emmanuel; Vanham, Guido; Davis, David; Janssens, Wouter

    2009-11-01

    Studies of viruses taken from individuals with broad cross-neutralizing antibodies against primary isolates may reveal novel antibody specificities and their associated epitopes that could be useful for immunogen design. We report on the Env antigenic variability of a slow progressing HIV-1 subtype A-infected donor with consistent broad cross-neutralizing antibodies during the second decade of disease progression after vertical transmission. The Env evolution is characterized by a genetic shift to variants with altered V1-V5 loop sequences, marked by consecutive changes in V1, V4-V5, and C3 and largely conserved V2 and V3 loop sequences. Major V1 Env sequence expansion, variation by a duplication event, and cumulative addition of cysteine residues and potential N-glycosylation sites over time may contribute to escape from antibody pressure directed to Env receptor domains by changing the exposure of neutralization-sensitive epitopes. Conservation of functional epitopes may correlate with the continued presence of broad cross-neutralizing antibodies.

  12. CBF tomograms with (/sup 99m/Tc-HM-PAO in patients with dementia (Alzheimer type and HIV) and Parkinson's disease--initial results

    Energy Technology Data Exchange (ETDEWEB)

    Costa, D.C.; Ell, P.J.; Burns, A.; Philpot, M.; Levy, R.

    1988-12-01

    We present preliminary data on the utility of functional brain imaging with (99mTc)-d,l-HM-PAO and single photon emission computed tomography (SPECT) in the study of patients with dementia of the Alzheimer type (DAT), HIV-related dementia syndrome, and the on-off syndrome of Parkinson's disease. In comparison with a group of age-matched controls, the DAT patients revealed distinctive bilateral temporal and posterior parietal deficits, which correlate with detailed psychometric evaluation. Patients with amnesia as the main symptom (group A) showed bilateral mesial temporal lobe perfusion deficits (p less than 0.02). More severely affected patients (group B) with significant apraxia, aphasia, or agnosia exhibited patterns compatible with bilateral reduced perfusion in the posterior parietal cortex, as well as reduced perfusion to both temporal lobes, different from the patients of the control group (p less than 0.05). SPECT studies of HIV patients with no evidence of intracraneal space occupying pathology showed marked perfusion deficits. Patients with Parkinson's disease and the on-off syndrome studied during an on phase (under levodopa therapy) and on another occasion after withdrawal of levodopa (off) demonstrated a significant change in the uptake of (99mTc)-d,l-HM-PAO in the caudate nucleus (lower on off) and thalamus (higher on off). These findings justify the present interest in the functional evaluation of the brain of patients with dementia. (99mTc)-d,l-HM-PAO and regional cerebral blood flow (rCBF)/SPECT appear useful and highlight individual disorders of flow in a variety of neuropsychiatric conditions.

  13. Prevalence and Type Distribution of Human Papillomavirus Among 1813 Men in Tanzania and the Relationship to HIV Status

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Iftner, Thomas; Mwaiselage, Julius

    2013-01-01

    Infection with high-risk (HR) human papillomavirus (HPV) is associated with penile cancer in men, cervical cancer in women, and anal cancer and certain types of head and neck cancers in both sexes. Few studies have assessed the prevalence and type distribution of HPV among men in sub-Saharan Africa...

  14. Probability analysis of variational crystallization and its application to gp120, the exterior envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1).

    Science.gov (United States)

    Kwong, P D; Wyatt, R; Desjardins, E; Robinson, J; Culp, J S; Hellmig, B D; Sweet, R W; Sodroski, J; Hendrickson, W A

    1999-02-12

    The extensive glycosylation and conformational mobility of gp120, the envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1), pose formidable barriers for crystallization. To surmount these difficulties, we used probability analysis to determine the most effective crystallization approach and derive equations which show that a strategy, which we term variational crystallization, substantially enhances the overall probability of crystallization for gp120. Variational crystallization focuses on protein modification as opposed to crystallization screening. Multiple variants of gp120 were analyzed with an iterative cycle involving a limited set of crystallization conditions and biochemical feedback on protease sensitivity, glycosylation status, and monoclonal antibody binding. Sources of likely conformational heterogeneity such as N-linked carbohydrates, flexible or mobile N and C termini, and variable internal loops were reduced or eliminated, and ligands such as CD4 and antigen-binding fragments (Fabs) of monoclonal antibodies were used to restrict conformational mobility as well as to alter the crystallization surface. Through successive cycles of manipulation involving 18 different variants, we succeeded in growing six different types of gp120 crystals. One of these, a ternary complex composed of gp120, its receptor CD4, and the Fab of the human neutralizing monoclonal antibody 17b, diffracts to a minimum Bragg spacing of at least 2.2 A and is suitable for structural analysis.

  15. An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

    Directory of Open Access Journals (Sweden)

    Mariaconcetta Sicurella

    Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

  16. HIV-2 and its neurological manifestations

    African Journals Online (AJOL)

    The human immunodeficiency virus type 2 (HIV-2) produces a similar spectrum of illness as HIV-1, including. AIDS, and is clinically indistinguishable. There is evidence that it is less pathogenic, with a longer natural history. HIV-. 2 infection is endemic in West Africa, especially in the former Portuguese and French colonies.

  17. Factors are not the same for risk of stopping exclusive breast-feeding and introducing different types of liquids and solids in HIV-affected communities in Ghana.

    Science.gov (United States)

    Marquis, Grace S; Lartey, Anna; Perez-Escamilla, Rafael; Mazur, Robert E; Brakohiapa, Lucy; Birks, Katherine A

    2016-07-01

    Exclusive breast-feeding (EBF) for 6 months supports optimal infant growth, health and development. This paper examined whether maternal HIV status was associated with EBF and other infant feeding practices. Pregnant women were enrolled after HIV counselling, and their babies were followed up for up to 1 year. Data on household socio-economics and demographics, maternal characteristics and infants' daily diet were available for 482 infants and their mothers (150 HIV-positive (HIV-P), 170 HIV-negative (HIV-N) and 162 HIV-unknown (HIV-U)). Survival analyses estimated median EBF duration and time to introduction of liquids and foods; hazards ratios (HR) used data from 1-365 and 1-183 d, adjusting for covariates. Logistic regression estimated the probability of EBF for 6 months. Being HIV-P was associated with a shorter EBF duration (139 d) compared with HIV-N (163 d) and HIV-U (165 d) (P=0·004). Compared with HIV-N, being HIV-P was associated with about a 40 % higher risk of stopping EBF at any time point (HR 1·39; 95 % CI 1·06, 1·84; P=0·018) and less than half as likely to complete 6 months of EBF (adjusted OR 0·42; 95 % CI 0·22, 0·81; P=0·01). Being HIV-P tended to be or was associated with a higher risk of introducing non-milk liquids (HR 1·34; 95 % CI 0·98, 1·83; P=0·068), animal milks (HR 2·37; 95 % CI 1·32, 4·24; P=0·004) and solids (HR 1·56; 95 % CI 1·10, 2·22; P=0·011) during the first 6 months. Weight-for-age Z-score was associated with EBF and introducing formula. Different factors (ethnicity, food insecurity, HIV testing strategy) were associated with the various feeding behaviours, suggesting that diverse interventions are needed to promote optimal infant feeding.

  18. HIV-1 replication in macrophages

    NARCIS (Netherlands)

    Kootstra, N.A.

    1999-01-01

    Lentiviruses such as the human immunodeficiency virus type 1 (HIV-1) are considered to be unique amongst the retroviruses due to their ability to replicate in macrophages, which are often referred to as non-dividing cells. The studies described in this thesis focus on the ability of HIV-1 to

  19. Env-2dCD4 S60C complexes act as super immunogens and elicit potent, broadly neutralizing antibodies against clinically relevant human immunodeficiency virus type 1 (HIV-1).

    Science.gov (United States)

    Killick, Mark A; Grant, Michelle L; Cerutti, Nichole M; Capovilla, Alexio; Papathanasopoulos, Maria A

    2015-11-17

    The ability to induce a broadly neutralizing antibody (bNAb) response following vaccination is regarded as a crucial aspect in developing an effective vaccine against human immunodeficiency virus type 1 (HIV-1). The bNAbs target the HIV-1 envelope glycoprotein (Env) which is exposed on the virus surface, thereby preventing cell entry. To date, conventional vaccine approaches such as the use of Env-based immunogens have been unsuccessful. We expressed, purified, characterized and evaluated the immunogenicity of several unique HIV-1 subtype C Env immunogens in small animals. Here we report that vaccine immunogens based on Env liganded to a two domain CD4 variant, 2dCD4(S60C) are capable of consistently eliciting potent, broadly neutralizing antibody responses in New Zealand white rabbits against a panel of clinically relevant HIV-1 pseudoviruses. This was irrespective of the Env protein subtype and context. Importantly, depletion of the anti-CD4 antibodies appeared to abrogate the neutralization activity in the rabbit sera. Taken together, this data suggests that the Env-2dCD4(S60C) complexes described here are "super" immunogens, and potentially immunofocus antibody responses to a unique epitope spanning the 2dCD4(60C). Recent data from the two available anti-CD4 monoclonal antibodies, Ibalizumab and CD4-Ig (and bispecific variants thereof) have highlighted that the use of these broad and potent entry inhibitors could circumvent the need for a conventional vaccine targeting HIV-1. Overall, the ability of the unique Env-2dCD4(S60C) complexes to elicit potent bNAb responses has not been described previously, reinforcing that further investigation for their utility in preventing and controlling HIV-1/SIV infection is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The incidence rate of HIV type-1 drug resistance in patients on antiretroviral therapy: a nationwide population-based Danish cohort study 1999-2005

    DEFF Research Database (Denmark)

    Audelin, A.M.; Lohse, N.; Obel, N.

    2009-01-01

    failure (HIV RNA>1,000 copies/ml). We estimated annual IRs of new resistance mutations towards nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors (PI), and of new specific resistance mutations. RESULTS: A total of 1,829 individuals were observed for 7......BACKGROUND: Newer antiretroviral treatment regimens for HIV carry a lower risk of inducing drug resistance mutations. We estimated changes in incidence rates (IRs) of new mutations in HIV-infected individuals receiving highly active antiretroviral therapy (HAART). METHODS: Population-based data...... were obtained from the Danish HIV Cohort Study and the Danish HIV Sequence Database. We included treatment-naive patients initiating HAART after December 1997 and computed time to first drug resistance mutation, identified as new mutations detected within 1 year after a 60-day period of treatment...

  1. Incidence of Co-Infections of HIV, Herpes Simplex Virus Type 2 and Syphilis in a Large Cohort of Men Who Have Sex with Men in Beijing, China

    Science.gov (United States)

    Zhang, Zheng; Wang, Zixin; Qi, Xiao; Ruan, Yuhua; Zhou, Yunhua; Li, Chunrong; Luo, Fengji; Lau, Joseph T. F.

    2016-01-01

    Background The HIV-epidemic among MSM in China has worsened. In this key population, prevalence of HSV-2 and syphilis infection and co-infection with HIV is high. Methods A longitudinal study was conducted (n = 962) in Beijing, China, with three overlapping cohorts (n = 857, 757 and 760) consisting of MSM that were free from pairs of infections of concern (i.e. HIV-HSV-2, HIV-syphilis, HSV-2-syphilis) at baseline to estimate incidence of HIV, HSV-2, syphilis, and those of co-infection. Results The incidence of HIV, HSV-2 and syphilis in the overall cohort was 3.90 (95% CI = 2.37, 5.43), 7.87 (95% CI = 5.74, 10.00) and 6.06 (95% CI = 4.18, 7.94) cases per 100 person-years (PYs), respectively. The incidence of HIV-HSV-2, HIV-Syphilis and HSV-2-Syphilis co-infections was 0.30 (95% CI = 0.29, 0.88), 1.02 (95% CI = 0.13, 2.17) and 1.41 (95% CI: 0.04, 2.78) cases per 100 PYs, respectively, in the three sub-cohorts constructed for this study. Conclusions The incidence of HIV, HSV-2 and syphilis was very high and those of their co-infections were relatively high. Such co-infections have negative impacts on the HIV/STI epidemics. Prevention practices need to take such co-infections into account. PMID:26820145

  2. Analytical Performances of Human Immunodeficiency Virus Type 1 RNA-Based Amplix® Real-Time PCR Platform for HIV-1 RNA Quantification

    Directory of Open Access Journals (Sweden)

    Christian Diamant Mossoro-Kpinde

    2016-01-01

    Full Text Available Objectives. We evaluated the performances of Amplix real-time PCR platform developed by Biosynex (Strasbourg, France, combining automated station extraction (Amplix station 16 Dx and real-time PCR (Amplix NG, for quantifying plasma HIV-1 RNA by lyophilized HIV-1 RNA-based Amplix reagents targeting gag and LTR, using samples from HIV-1-infected adults from Central African Republic. Results. Amplix real-time PCR assay showed low limit of detection (28 copies/mL, across wide dynamic range (1.4–10 log copies/mL, 100% sensitivity and 99% specificity, high reproducibility, and accuracy with mean bias < 5%. The assay showed excellent correlations and concordance of 95.3% with the reference HIV-1 RNA load assay (Roche, with mean absolute bias of +0.097 log copies/mL by Bland-Altman analysis. The assay was able to detect and quantify the most prevalent HIV-1 subtype strains and the majority of non-B subtypes, CRFs of HIV-1 group M, and HIV-1 groups N and O circulating in Central Africa. The Amplix assay showed 100% sensitivity and 99.6% specificity to diagnose virological failure in clinical samples from antiretroviral drug-experienced patients. Conclusions. The HIV-1 RNA-based Amplix real-time PCR platform constitutes sensitive and reliable system for clinical monitoring of HIV-1 RNA load in HIV-1-infected children and adults, particularly adapted to intermediate laboratory facilities in sub-Saharan Africa.

  3. Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat.

    Science.gov (United States)

    Tang, Qiao; Qin, Di; Lv, Zhigang; Zhu, Xiaolei; Ma, Xinting; Yan, Qin; Zeng, Yi; Guo, Yuanyuan; Feng, Ninghan; Lu, Chun

    2012-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for Kaposi's sarcoma (KS) development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1) Tat and herpes simplex virus 1 (HSV-1) were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2) to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB) signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS (AIDS-KS) patients.

  4. Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat.

    Directory of Open Access Journals (Sweden)

    Qiao Tang

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV infection was necessary but not sufficient for Kaposi's sarcoma (KS development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1 Tat and herpes simplex virus 1 (HSV-1 were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2 to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS-related KS (AIDS-KS patients.

  5. Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.

    Science.gov (United States)

    Gray, Glenda E; Moodie, Zoe; Metch, Barbara; Gilbert, Peter B; Bekker, Linda-Gail; Churchyard, Gavin; Nchabeleng, Maphoshane; Mlisana, Koleka; Laher, Fatima; Roux, Surita; Mngadi, Kathryn; Innes, Craig; Mathebula, Matsontso; Allen, Mary; McElrath, M Julie; Robertson, Michael; Kublin, James; Corey, Lawrence

    2014-05-01

    The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data. HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18-35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539. Between Jan 24, 2007, and Sept 19, 2007, 801 participants (26·7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31-42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1·70, 95% CI 1·13-2·55; p=0·01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7·7% [95% CI 6·2-9·5] for vaccine recipients vs 8·8% [7·1-10·7] for placebo recipients; p=0·40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients. The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological

  6. Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series.

    Directory of Open Access Journals (Sweden)

    Renata Báez-Saldaña

    Full Text Available Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART programs and epidemiology of infectious diseases.To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS.We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions.We studied 308 patients, of whom 206 (66.9% had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR: 30-150]. Seventy-five (24.4% cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP (n = 142, tuberculosis (n = 63, and bacterial community-acquired pneumonia (n = 60 were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR: 0.245, 95% Confidence Interval (CI: 0.08-0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06-0.75 of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses.HAART for 180 days or more was associated with 79% decrease in all-cause in-hospital mortality and lower

  7. Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series.

    Science.gov (United States)

    Báez-Saldaña, Renata; Villafuerte-García, Adriana; Cruz-Hervert, Pablo; Delgado-Sánchez, Guadalupe; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Melchor-Romero, Ada; García-García, Lourdes

    2015-01-01

    Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases. To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS. We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions. We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR): 30-150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08-0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06-0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses. HAART for 180 days or more was associated with 79% decrease in all-cause in-hospital mortality and lower

  8. 75 FR 70270 - Submission for OMB Review; Comment Request; Pretesting of NIAID's Biomedical HIV Prevention...

    Science.gov (United States)

    2010-11-17

    ... NIAID's Biomedical HIV Prevention Research Communication Messages SUMMARY: In compliance with the... Collection: Title: Pretesting of NIAID's Biomedical HIV Prevention Research Communication Messages. Type of... biomedical HIV prevention research. The primary objectives of the pretests are to (1) Assess audience...

  9. Effects of biscuit-type feeding supplementation on the neurocognitive outcomes of HIV-affected school-age children: a randomized, double-blind, controlled intervention trial in Kenya

    Directory of Open Access Journals (Sweden)

    Kek Khee Loo

    2017-12-01

    Full Text Available Objective: To determine if meat or soy protein dietary supplementation will enhance the neurocognitive performance of HIV-affected children at-risk of malnutrition and food insecurity. Methods: A randomized, double-blind, controlled intervention trial evaluated the effect of nutritional supplementation on the neurocognitive outcomes of 49 HIV-affected school-age children in western Kenya. The intervention consisted in providing the mother, target child, and siblings with one of three isocaloric biscuit-type supplements – soy, wheat, or beef – on 5 days per week for 18 months. Neurocognitive outcomes of the target children were assessed by a battery of eight measures and followed up longitudinally for up to 24 months. Results: Mixed effects modeling demonstrated significant differences in the rates of increase over time among all three groups (F test degrees of freedom of 2, P<0.05 for Raven’s progressive matrices performance, but not for verbal meaning, arithmetic, digit span backward, forward, and total, embedded figure test, and Beery visual–motor integration scores. Conclusion: HIV-affected school-age children provided with soy protein supplementation showed greater improvement in nonverbal cognitive (fluid intelligence performance compared with peers who received isocaloric beef or wheat biscuits. Soy nutrients may have an enhancing effect on neurocognitive skills in HIV-affected school-age children.

  10. Socio-demographic and epidemiological characteristics associated with human immunodeficiency virus type I (HIV-1 infection in HIV-1-explosed but uninfected individuals, and in HIV-1-infected patients from a southern brasilian population Características sociodemográficas e epidemiológicas associadas com a infecção pelo vírus da imunodeficiência humana tipo 1 (HIV-1 em indivíduos expostos ao HIV-1 mas não infectados e em pacientes infectados pelo HIV-1, provenientes da população da região Sul do Brasil

    Directory of Open Access Journals (Sweden)

    Edna Maria Vissoci Reiche

    2005-10-01

    Full Text Available The ability to control human immunodeficiency virus type 1 (HIV-1 infection and progression of the disease is regulated by host and viral factors. This cross-sectional study describes the socio-demographic and epidemiological characteristics associated with HIV-1 infection in 1,061 subjects attended in Londrina and region, south of Brazil: 136 healthy individuals (Group 1, 147 HIV-1-exposed but uninfected individuals (Group 2, 161 HIV-1-infected asymptomatic patients (Group 3, and 617 patients with AIDS (Group 4. Data were obtained by a standardized questionnaire and serological tests. The age of the individuals ranged from 15.1 to 79.5 years, 54.0% and 56.1% of the Groups 3 and 4 patients, respectively, were men. The major features of groups 2, 3, and 4 were a predominance of education level up to secondary school (55.8%, 60.2% and 62.4%, respectively, sexual route of exposure (88.4%, 87.0% and 82.0%, respectively, heterosexual behavior (91.8%, 75.2% and 83.7%, respectively, and previous sexually transmitted diseases (20.4%, 32.5%, and 38.1%, respectively. The patients with AIDS showed the highest rates of seropositivity for syphilis (25.6%, of anti-HCV (22.3%, and anti-HTLV I/II obtained by two serological screening tests (6.2% and 6.8%, respectively. The results documenting the predominant characteristics for HIV-1 infection among residents of Londrina and region, could be useful for the improvement of current HIV-1 prevention, monitoring and therapeutic programs targeted at this population.Este estudo transversal descreve as principais características sociodemográficas e epidemiológicas associadas com a infecção pelo HIV-1 em 1.061 indivíduos atendidos em Londrina e região, Sul do Brasil: 136 indivíduos saudáveis (Grupo 1, 147 indivíduos expostos ao HIV-1 mas não infectados (Grupo 2, 161 pacientes infectados pelo HIV-1 assintomáticos (Grupo 3 e 617 pacientes com aids (Grupo 4. Os dados foram obtidos pela aplicação de um

  11. Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA protein in a human immunodeficiency virus type 1 (HIV-1 derivative that has simian immunodeficiency virus (SIVmac239 vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

    Directory of Open Access Journals (Sweden)

    Adachi Akio

    2009-08-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5 of capsid protein (CA and the entire SIVmac239 vif gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7 of HIV type 2 (HIV-2 CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α. Results In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and vif with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells. Conclusion We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys in vivo.

  12. Barriers and facilitators associated with HIV testing uptake in South African health facilities offering HIV Counselling and Testing

    Directory of Open Access Journals (Sweden)

    Neo Mohlabane

    2016-10-01

    Objective: An HCT survey was carried out to ascertain barriers and facilitators for HIV testing in South Africa. Methods: A cross-sectional survey of 67 HCT-offering health facilities in 8 South African provinces was undertaken. Individuals (n = 489 who had not tested for HIV on the day of the site visit were interviewed on awareness of HCT services, HIV testing history and barriers to HIV testing. Frequencies were run to describe the sample characteristics, barriers and facilitators to HIV testing. Bivariate and multivariate logistic regression was usedt o identify the association between never tested for HIV with socio-demographics, awareness of HCT services and type of HCT facilities. Results: In all 18.1% participants never had an HIV test. Major barriers to HCT uptake comprise being scared of finding out one's HIV test result or what people may say, shyness or embarrassment, avoidance of divulging personal information to health workers and fear of death. In multivariate analysis the age group 55 years and older, and not being recommended to have an HIV test were associated with never had an HIV test. Potential facilitators for HIV testing include community or household HIV testing, providing incentives for those who test for HIV, mandatory HIV testing and disclosure of HIV status by those who test HIV positive. Conclusion: The benefits of HCT which include the reduction of HIV transmission, the availability of HIV care and treatment needs to be emphasized to enhance HCT uptake.

  13. Short communication: evaluating the level of expressed HIV type 1 gp120 and gag proteins in the vCP1521 vector by two immunoplaque methods.

    Science.gov (United States)

    Azizi, Ali; Edamura, Kerrie Nichol; Leung, Glenda; Gisonni-Lex, Lucy; Mallet, Laurent

    2013-02-01

    Over the past few years, several recombinant ALVAC constructs have been used as delivery systems in various vaccine research studies and trials. The ALVAC-HIV vCP1521 vector has been used as a vaccine delivery system in the RV144 study, a phase III HIV study that displayed over 31% protective efficacy. One of the important parameters for evaluating the potency of an ALVAC construct is the stable expression of proteins encoded by the inserted genes. Herein, the expression of inserted gp120 and gag genes in two manufactured ALVAC-HIV vCP1521 lots have been determined by two immunoplaque methods (dish and plaque lift). Both methods were specific and robust and demonstrated that the ALVAC-HIV vCP1521 lots were able to express gp120 and gag proteins in over 99% of the infectious plaques.

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... dangerous weight loss, diarrhea, and a type of cancer called Kaposi's sarcoma. 1 Some hopeful news is ... cognitive impairment among methamphetamine abusers than among HIV patients who do not abuse drugs. In animal studies, ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and other organs, and they frequently suffer dangerous weight loss, diarrhea, and a type of cancer called Kaposi's ... gov : This blog fosters public discussions on using new media effectively in response to HIV/AIDS, as ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and a type of cancer called Kaposi's sarcoma. 1 Some hopeful news is that, in recent years, ... increase the amount of HIV in brain cells 1 . Drug abuse treatment. Since the late 1980s, research ...

  17. Correlation of prospective and cross-sectional measures of HIV type 1 incidence in a higher-risk cohort in Ho Chi Minh City, Vietnam.

    Science.gov (United States)

    Sexton, Connie J; Costenbader, Elizabeth C; Vinh, Dang Thi Nhat; Chen, Pai Lien; Hoang, Tran Vu; Lan, Nguyen Thi Hoang; Feldblum, Paul; Kim, Andrea; Giang, Le Truong

    2012-08-01

    The primary aim of this study was to estimate HIV incidence within a high-risk population in Ho Chi Minh City (HCMC), Vietnam using both cross-sectional and prospective methodologies. A secondary aim was to develop a local correction factor for the BED and avidity index incidence assays. The research study design consisted of three phases: (1) cross-sectional, (2) prospective, and (3) BED false recent (BED FR). A total of 1619 high-risk, sexually active individuals were enrolled in the cross-sectional phase and 355 of the opiate-negative, HIV-negative women were subsequently enrolled in the prospective phase. Four-hundred and three men and women with known HIV infection duration of greater than 12 months were enrolled in the BED FR phase. The HIV prevalence for all participants in the cross-sectional phase was 15.8%. HIV incidence in the cross-sectional group was estimated using the BED IgG capture assay and AxSYM avidity index assay for recent HIV infection and incidence within the prospective cohort was determined by observations of HIV seroconversion. HIV incidence in opiate-negative women was estimated using the BED assay to be 0.8% unadjusted and 0.5% after applying the locally derived BED false recent rate of 1.7%; no seroconversions were observed in the prospective cohort. We also screened the cross-sectional samples for evidence of acute infection using nucleic acid testing, 4th generation HIV EIA, and SMARTube coupled with Genscreen and Determine diagnostic tests; no confirmed acute infections were identified by any method. HIV incidence within this opiate-negative study population was low and incidence estimates from the two methods compared favorably with each other. Incidence estimates and false recent rates using the AxSYM assay were higher: AI FRR of 2.7% and adjusted incidence of 1.7% per year (95% CI, 0.6, 2.8). By comparison, both HIV prevalence and incidence estimates for the opiate-positive group were higher.

  18. Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection

    DEFF Research Database (Denmark)

    Kowalska, Justyna D; Mocroft, Amanda; Blaxhult, Anders

    2007-01-01

    The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral...... load measured 6 months prior to starting cART was included in the analyses. Anemia was defined as mild (...

  19. Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients

    Directory of Open Access Journals (Sweden)

    Vaishali Kolgiri Honnapurmath

    2017-01-01

    Full Text Available Background and Objectives: Insulin resistance (IR is frequent in human immunodeficiency virus (HIV infection and may be related to antiretroviral therapy (ART. Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA damage in HIV-1-infected patients with different ART status. Materials and Methods: In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG, as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment. Results: All subjects were randomly selected and grouped as HIV-negative (control group (n = 300, HIV-positive without ART (n = 100, HIV-positive with ART first line (n = 100, and HIV-positive with ART second line (n = 100. IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509 P < 0.001. Interpretation and Conclusions: In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

  20. Confirmation of Putative HIV-1 Group P in Cameroon▿

    OpenAIRE

    Vallari, Ana; Holzmayer, Vera; Harris, Barbara; Yamaguchi, Julie; Ngansop, Charlotte; Makamche, Florence; Mbanya, Dora; Kaptué, Lazare; Ndembi, Nicaise; Gürtler, Lutz; Devare, Sushil; Brennan, Catherine A.

    2010-01-01

    We report the second human immunodeficiency virus (HIV) belonging to the new HIV type 1 (HIV-1) group P lineage that is closely related to the simian immunodeficiency virus found in gorillas. This virus was identified in an HIV-seropositive male hospital patient in Cameroon, confirming that the group P virus is circulating in humans. Results from screening 1,736 HIV-seropositive specimens collected in Cameroon indicate that HIV-1 group P infections are rare, accounting for only 0.06% of HIV i...

  1. Impact of HIV-1, HIV-2, and HIV-1+2 dual infection on the outcome of tuberculosis.

    Science.gov (United States)

    Wejse, C; Patsche, C B; Kühle, A; Bamba, F J V; Mendes, M S; Lemvik, G; Gomes, V F; Rudolf, F

    2015-03-01

    HIV-1 infection has been shown to impact the outcome of patients with tuberculosis (TB), but data regarding the impact of HIV-2 on TB outcomes are limited. The aim of this study was to assess the impact of HIV types on mortality among TB patients in Guinea-Bissau and to examine the predictive ability of the TBscoreII, a clinical score used to assess disease severity. In a prospective follow-up study, we examined the prevalence of HIV-1, HIV-2, and HIV-1+2 co-infection in TB patients in Guinea-Bissau, and the impact on outcomes at 12 months of follow-up. We included all adult TB patients in an observational TB cohort at the Bandim Health Project (BHP) in Guinea-Bissau between 2003 and 2013 and assessed survival status at 12 months after the start of treatment. A total 1312 patients were included; 499 (38%) were female (male/female ratio 1.6). Three hundred and seventy-nine patients were HIV-infected: 241 had HIV-1, 93 had HIV-2, and 45 were HIV-1+2 dual infected. The HIV type-associated risk of TB was 6-fold higher for HIV-1, 7-fold higher for HIV-1+2 dual infection, and 2-fold higher for HIV-2 compared with the HIV-uninfected. Of the patients included, 144 (11%) died, 62 (12%) among females and 82 (9%) among males (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.64-1.30; p=0.596). Compared to male patients, female patients were younger (1 year younger, 95% CI 0.5-2; p=0.04), reported a longer duration of symptoms (14 days longer, 95% CI 4-25; p=0.003), and had a higher TBscoreII (0.5 points more, 95% CI 0.3-0.7; pHIV-infected (36% vs. 25%; pHIV infection increased the mortality risk, with HIV-1 infection displaying the highest HR (5.0, 95% CI 3.5-7.1), followed by HIV-1+2 (HR 4.2, 95% CI 2.2-7.8) and HIV-2 (HR 2.1, 95% CI 1.2-3.8). A TBscoreII ≥4 was associated with increased mortality (HR 2.2, 95% CI 1.5-3.1). Significantly increased HRs were found for signs of wasting; a BMI HIV type-associated risk of TB was much higher for HIV-1 patients and higher but

  2. Quantifying sexual exposure to HIV within an HIV-serodiscordant relationship: development of an algorithm.

    Science.gov (United States)

    Fox, Julie; White, Peter J; Weber, Jonathan; Garnett, Geoff P; Ward, Helen; Fidler, Sarah

    2011-05-15

    The risk of acquiring HIV from a single sexual contact varies enormously reflecting biological and behavioural characteristics of both infected and uninfected partners. Accurate information on HIV transmission risk is required to construct evidence-based risk reduction practices for individuals, to direct the provision of prevention strategies at the population level, and enable the definition, quantification and comparison of true exposure in individuals termed 'exposed uninfected' within clinical trials. Following a systematic review of current literature on HIV transmission estimates, an HIV risk score was developed, incorporating weighted risk factors into a Bernoulli mathematical model, allowing quantification of overall risk of HIV acquisition within HIV-serodiscordant partnerships. The HIV risk score enumerates the relative risk of HIV acquisition from HIV-positive partners incorporating the type and frequency of specific sex acts, the index case HIV plasma viral load and stage of disease, and the presence of genital ulcer disease in either partner and pregnancy, HSV-2 seropositivity, and circumcision status (men only) in the HIV-negative partner. Key determinants of HIV exposure risk can be incorporated into a mathematical model in order to quantify individual relative risks of HIV acquisition. Such a model can facilitate comparisons within clinical trials of exposed uninfected individuals and facilitate interventions to reduce HIV transmission.

  3. Short communication: SDF1-3'A gene mutation is correlated with increased susceptibility to HIV type 1 infection by sexual transmission in Han Chinese.

    Science.gov (United States)

    Wang, Yueyun; Wang, Xiaohui; Peng, Ji; Chen, Lin; Cheng, Jinquan; Nie, Shaofa; Feng, Tiejian; Zhao, Guanglu; Zhao, Jin; Shi, Xiangdong

    2008-11-01

    Limited information is available on host genetic polymorphisms that confer resistance to HIV-1 infection in Han Chinese who persistently remain seronegative (HEPS) despite high exposure to HIV-1 through unprotected sexual activity with known HIV-1-seropositive spouses or long-term sexual partners. The aim of this study was to investigate the correlation of CCR5-Delta32, CCR2b-64I, and SDF1-3'A polymorphisms with susceptibility to HIV-1 infection through sexual transmission in Han Chinese. A cross-sectional study was used to analyze the differences in allelic frequencies of CCR5-Delta32, CCR2b-64I, and SDF1-3'A among HEPS, healthy HIV-unexposed individuals, and HIV-1-seropositive individuals. Restriction fragment length polymorphism (RFLP) analysis was used for genotype determination. The CCR5-Delta32 mutation was not detected in the three groups (n = 260). The allelic frequencies of CCR2b-64I were 21.57%, 21.63%, and 22.12% in the three groups, respectively. There was no significant difference among the three groups in CCR2b-64I distribution. The allelic frequencies of SDF1-3'A were 20.19%, 28.37%, and 29.33% in the three groups, respectively. There was a significant difference in the allelic distribution of SDF1-3'A between HEPS and healthy HIV-unexposed individuals (p = 0.023), as well as between HEPS and HIV-1-seropositive individuals (p = 0.049). Statistical analysis showed that the allelic distributions on CCR2b-64I and SDF1-3'A were in equilibrium according to the Hardy-Weinberg equation. The mutant genotypes of CCR5-Delta32 and CCR2b-64I were not correlated with HIV-1 infection through sexual transmission in Han Chinese. SDF1- 3'A was associated with a high risk of HIV-1 infection through sexual transmission in Han Chinese.

  4. 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.

  5. Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC

    Directory of Open Access Journals (Sweden)

    Yu Xu G

    2007-08-01

    Full Text Available Abstract Background The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC, which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV-1-specific T cell responses at single peptide level with overlapping peptides (OLP covering the whole concensus clades B and C proteome. Results The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413 of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574 can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm3 were observed when compared to those with less than 200/mm3 or more than 400/mm3, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load. Conclusion This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross-reactivity were observed, though similar patterns of overall immune responses were

  6. INCIDENCE OF LYMPHOMAS AND OTHER CANCERS IN HIV-INFECTED AND HIV-UNINFECTED PATIENTS WITH HEMOPHILIA

    NARCIS (Netherlands)

    RABKIN, CS; HILGARTNER, MW; HEDBERG, KW; ALEDORT, LM; HATZAKIS, A; EICHINGER, S; EYSTER, ME; WHITE, GC; KESSLER, CM; LEDERMAN, MM; DEMOERLOOSE, P; BRAY, GL; COHEN, AR; ANDES, WA; MANCOJOHNSON, M; SCHRAMM, W; KRONER, BL; BLATTNER, WA; GOEDERT, JJ

    1992-01-01

    Objective. - To determine the types and rates of cancers occurring in excess in the presence of infection with the human immunodeficiency virus type 1 (HIV-1). Design. - Cohort analytic study of HIV-infected and HIV-uninfected subjects followed for up to 12 years. Setting. - Fifteen hemophilia

  7. Is an HIV vaccine possible?

    Directory of Open Access Journals (Sweden)

    Nancy A. Wilson

    Full Text Available The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5 expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.

  8. T CD4+ cells count among patients co-infected with human immunodeficiency virus type 1 (HIV-1 and human T-cell leukemia virus type 1 (HTLV-1: high prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM Contagens de células T CD4+ na co-infecção HIV-1 e HTLV-1: alta prevalência da paraparesia espástica tropical/mielopatia associada ao HTLV-1

    Directory of Open Access Journals (Sweden)

    Jorge Casseb

    2007-08-01

    Full Text Available INTRODUCTION: HIV positive patients co-infected with HTLV-1 may have an increase in their T CD4+ cell counts, thus rendering this parameter useless as an AIDS-defining event. OBJECTIVE: To study the effects induced by the co-infection of HIV-1 and HTLV-1 upon CD4+ cells. MATERIAL AND METHODS: Since 1997, our group has been following a cohort of HTLV-1-infected patients, in order to study the interaction of HTLV-1 with HIV and/or with hepatitis C virus (HCV, as well as HTLV-1-only infected asymptomatic carriers and those with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM. One hundred and fifty HTLV-1-infected subjects have been referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas", São Paulo. Twenty-seven of them were also infected with HIV-1 and HTLV-1-infection using two ELISAs and confirmed and typed by Western Blot (WB or polymerase chain reaction (PCR. All subjects were evaluated by two neurologists, blinded to the patient's HTLV status, and the TSP/HAM diagnostic was based on the World Health Organization (WHO classification. AIDS-defining events were in accordance with the Centers for Disease Control (CDC classification of 1988. The first T CD4+ cells count available before starting anti-retroviral therapy are shown compared to the HIV-1-infected subjects at the moment of AIDS defining event. RESULTS: A total of 27 HIV-1/HTLV-1 co-infected subjects were identified in this cohort; 15 already had AIDS and 12 remained free of AIDS. The median of T CD4+ cell counts was 189 (98-688 cells/mm³ and 89 (53-196 cells/mm³ for co-infected subjects who had an AIDS-defining event, and HIV-only infected individuals, respectively (p = 0.036. Eight of 27 co-infected subjects (30% were diagnosed as having a TSP/HAM simile diagnosis, and three of them had opportunistic infections but high T CD4+ cell counts at the time of their AIDS- defining event. DISCUSSION: Our results indicate that higher T CD4+ cells

  9. Evaluation of supplemental testing with the Multispot HIV-1/HIV-2 Rapid Test and APTIMA HIV-1 RNA Qualitative Assay to resolve specimens with indeterminate or negative HIV-1 Western blots.

    Science.gov (United States)

    Linley, Laurie; Ethridge, Steven F; Oraka, Emeka; Owen, S Michele; Wesolowski, Laura G; Wroblewski, Kelly; Landgraf, Kenneth M; Parker, Monica M; Brinson, Myra; Branson, Bernard M

    2013-12-01

    The use of Western blot (WB) as a supplemental test after reactive sensitive initial assays can lead to inconclusive or misclassified HIV test results, delaying diagnosis. To determine the proportion of specimens reactive by immunoassay (IA) but indeterminate or negative by WB that could be resolved by alternative supplemental tests recommended under a new HIV diagnostic testing algorithm. Remnant HIV diagnostic specimens that were reactive on 3rd generation HIV-1/2 IA and either negative or indeterminate by HIV-1 WB from 11 health departments were tested with the Bio-Rad Multispot HIV-1/HIV-2 Rapid Test (Multispot) and the Gen-Probe APTIMA HIV-1 RNA Qualitative Assay (APTIMA). According to the new testing algorithm, 512 (89.8%) specimens were HIV-negative, 55 (9.6%) were HIV-1 positive (including 19 [3.3%] that were acute HIV-1 and 9 [1.6%] that were positive for HIV-1 by Multispot but APTIMA-negative), 2 (0.4%) were HIV-2 positive, and 1 (0.2%) was HIV-positive, type undifferentiated. 47 (21.4%) of the 220 WB-indeterminate and 8 (2.3%) of the 350 WB-negative specimens were HIV-1 positive. Applying the new HIV diagnostic algorithm retrospectively to WB-negative and indeterminate specimens, the HIV infection status could be established for nearly all of the specimens. IA-reactive HIV-infected persons with WB-negative results had been previously misclassified as uninfected, and HIV diagnosis was delayed for those with WB-indeterminate specimens. These findings underscore the limitations of the WB to confirm HIV infection after reactive results from contemporary 3rd or 4th generation IAs that can detect HIV antibodies several weeks sooner than the WB. Published by Elsevier B.V.

  10. No observable correlation between central nervous system side effects and EFV plasma concentrations in Japanese HIV type 1-infected patients treated with EFV containing HAART.

    Science.gov (United States)

    Takahashi, Masaaki; Ibe, Shiro; Kudaka, Yuichi; Okumura, Naoya; Hirano, Atsushi; Suzuki, Tatsuo; Mamiya, Naoto; Hamaguchi, Motohiro; Kaneda, Tsuguhiro

    2007-08-01

    The present study assessed the relationship between central nervous system (CNS) side effects and plasma concentrations of efavirenz (EFV) in Japanese HIV-1-infected patients. Subjects consisted of 69 HIV-1-infected patients (57 therapy-naive and 12 therapy-experienced patients) being treated using EFV in combination with other antiretroviral agents at the outpatient HIV clinic. Successful virological treatment was achieved in 61 patients. Eight patients discontinued EFV containing therapy because CNS symptoms did not resolve (four patients), EFV-specific mutations were detected (two patients), or skin rash was observed (two patients). Mean EFV plasma concentration for 61 effectively treated patients, measured at 15 h postdosing, was 2.42 microg/ml (range: 0.78-6.82 microg/ml). This EFV concentration range contributed to suppressed viral load in these Japanese patients. Adverse CNS effects were observed in 19 patients soon after therapy onset. These effects disappeared within 1 month except for four patients who suffered severe CNS side effects. Mean EFV plasma concentrations were not significantly different between subjects with (2.45 +/- 1.08 microg/ml) and without (2.42 +/- 1.40 microg/ml) CNS side effects. We concluded no correlation existed between the plasma EFV concentration and the emergence of CNS side effects in Japanese HIV-1-infected patients. Further investigations, enforced with the drug concentration measurement at earlier time points and more appropriate assessment of CNS symptoms, are required.

  11. Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control

    NARCIS (Netherlands)

    Ferreira, Manuel A. R.; Mangino, Massimo; Brumme, Chanson J.; Zhao, Zhen Zhen; Medland, Sarah E.; Wright, Margaret J.; Nyholt, Dale R.; Gordon, Scott; Campbell, Megan; McEvoy, Brian P.; Henders, Anjali; Evans, David M.; Lanchbury, Jerry S.; Pereyra, Florencia; Walker, Bruce D.; Haas, David W.; Soranzo, Nicole; Spector, Tim D.; de Bakker, Paul I. W.; Frazer, Ian H.; Montgomery, Grant W.; Martin, Nicholas G.; Agan, Brian; Agarwal, Shanu; Allen, Brady; Altidor, Sherly; Altschuler, Eric; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Andrady, Ushan; Angell, Teresa; Appelbaum, Jonathan; Arnold, Kathy; Arroyo, Julio; Arthur, Ernie; Barbaro, Daniel; Barrett, Tom; Barrie, William; Barthel, Vincent; Bartlett, Mary E.; Barton, Simon; Basden, Pat; Basgoz, Nesli; Bellos, Nicholas; Berger, Judith; Bernard, Annette; Bernard, Nicole; Blair, Donald; Bodner, Stanley; Bolan, Robert; Boudreaux, Emilie; Braun, James; Brndjar, Jon; Brooks, Edward; Brown, Kathy; Brown, Stephen; Bryant, Susan; Bryson, Rena; Buchbinder, Susan; Bullock, Diane; Burack, Jedidah; Busalacchi, Mary; Bush, Larry; Cafaro, Virginia; Campbell, John; Cardosi, Beth; Carlson, Rob; Carmichael, Kevin; Carr, Pat; Carrington, Mary; Cavacuiti, Chris; Celestin, Greg; Chaborek, Michele; Chau, John; Chez, Nancy; Cimoch, Paul; Cohen, Daniel E.; Cohn, Bruce; Cohn, Lillian; Conway, Brian; Cooper, David; Cooper, Julie; Cornellson, Brian; Cowles, Anastacia; Cox, David; Cox-Iyamu, Roxanne; Cuchural, George; Daily, Michael; Daly, Jennifer; Dang, Son; Davis, Benjamin; Davis, Kristine; de Koning, P.; DeCardi Hladek, Melissa; Dechter, Mark; Deeks, Steven; DeFoto, Joseph; DeJesus, Edwin; Dennis, Deborah T.; Dolan, Matthew; Duggan, Joan; Dunn, Michael; Egenes, Karen; Ellerin, Todd; Elliott, Kathy; Eron, Joe; Fangman, John; Ferlazzo, Helen; Figueroa, Yvette; Fiola, Terri; Fisk, Stuart; Flaherty, Maureen; Fleenor-Ford, Anita; Forster, Alice; Fralich, Todd; Francke, Elliott; Frankel, Renee; Freedburg, Kenneth; French, Neel; Fuchs, Jonathan D.; Fuller, John; Gaberman, Jonna I.; Gallant, Joel; Gandhi, Rajesh; Ganesan, Anurdha; Garcia, Efrain; Gardner, Adrian; Garver, Patricia; Gastaldo, Joseph; Gathe, Joseph; Gaultier, Cyril; Gebre, Wondwoosen; Gelman, Marcy; Gilman, Frank; Gilmore, John; Gimbarevsky, Boris; Glaser, Jordan; Goepfert, Paul; Good, Gary; Gottlieb, Michael; Goulston, Claudia; Grimm, William; Groger, Richard; Guiteau, Jacques; Gurley, T. Douglas; Haber, Stuart; Hale, Braden; Halpenny, Roberta; Hardin, Theresa; Hardy, W. David; Hargan, Todd; Harrigan, Richard; Haston, Janna; Hawkins, Trevor; Hellinger, Walter; Henderson, Robert; Henderson, Tom; Henry, Keith; Hermann, Susan; Hernandez, Salvador; Hicks, Claire; Hoffman, Robert; Holland, Chris; Horton, James; Hoskinson, Scott; Hsu, Ricky K.; Huber, Janice; Huhn, Gregory; Humphrey, Rene; Hupert, Mark; Hurtado, Rocio; Illeman, Mark; Israelski, Dennis; Jellinger, Robert; Jessen, Heiko; John, Mina; Johnson, Kay; Jones, Mary; Jordan, Wilbert; Kauffman, Carol; Keba, Anna; Khanlou, Homayoon; Killian, Rob; Kim, Arthur; Kim, David; Kinder, Ford; Kirchner, Jeff; Kish, Mary Ann; Kocurek, Kathryn; Kogelman, Laura; Kojic, E. Milu; Kortuis, Todd; Kovacs, Julia; Kreiswirth, Stacey; Kuldanek, Greg; Kurisu, Wayne; Lackey, Phillip; Ladan, Ahmadi; Lanzafame, Massimiliano; Lederman, Michael; Lee, David; Lee, Ed; Lee, Jenny; Lee, Marah; LeGrand, James; Lemoine, Janice; Levin, Steve; Levy, Jay; Liguori, Michael; Lin, Nina; Little, Susan; Livine, Richard; Llibre, Josep M.; Lopez, Al; Loutfy, Mona; Loy, Dawn; Lubarda, Barbara; Magee, Thomas; Maksvytis, Harvey; Man, Alan; Mancuso, Stacey; Marconi, Vincent; Markowitz, Martin; Marques, Rui; Martin, William; Mayer, Gal; Mayer, Kenneth; McCrone, Cindy; McDonald, Cheryl; McGhee, Theresa; McIntyre, Dawn; McLean, P. Scott; McNett, Michael; Mead, Hazel; Mechling, Katherine; Melia, Michael; Metroka, Craig; Meyer-Olson, Dirk; Michael, Brent; Miller, Andy; Montana, John; Montgomery, Kate; Morice, Anthony; Mounzer, Karam; Munoz, Michael; Nagin, Iris; Nahass, Ron; Ndung'u, Thumbi; Nelson, Sandra; Nielsen, Craig; Norene, David; Novales, Susan; O'Connor, David; O'Donnell, Laura; Oldfield, Edward; Olender, Susan; Ojikutu, Bisola; Owens, William; Panzer, Todd; Parks, Brad; Pattison, Julie; Pavlatos, Andy; Perlmutter, Aaron; Pierce, Michael Norman; Pollak, Deborah; Rowe, Emile; Pressnell, Richard; Price, Lawrence; Proia, Laurie; Prokesch, Richard; Prutch, Peter; Pujet, Heather; Rausch, Michael; Ravinshankar, Jayashree; Restrepo, Dalilah; Rhame, Frank; Richards, Constance; Richman, Douglas D.; Robbins, Gregory; Rose, Richard; Rosenthal, Daniel; Ross, Polly; Rubin, David; Rumbaugh, Elease; Sanchez, Will; Sanjana, Veeraf; Santiago, Stephen; Santos, Rene; Sax, Paul; Scherman, Debra; Schmidt, Wolfgang; Shrader, Shannon; Schuitemaker, Hanneke; Scribner, Anita; Sestak, Phillip; Shalit, Peter; Shay, William; Sherman, Jeffrey; Shirvani, Vivian; Sims, James; Sizemore, Jay; Slotten, Ross; Smiddy, Joseph; Sokol-Anderson, Marcia; Somogi, Rachel; Sordjan, Renee; Sosman, James; Stabile, Paul; Stapleton, Jack; Starrett, Sharee; Staszkow, Kaleo; Stearn, Ben; Stellbrink, Hans-Jurgen; Sterman, Lisa; Steyn, Tinus; Stone, David; Stone, Valerie; Ta, Ha; Tambussi, Giuseppe; Taplitz, Randy; Tashmia, Karen; Tavari, Daniel; Tedaldi, Ellen; Telenti, Amalio; Tierney, Marianne; Tillquist, Carolyn; Tosiello, Lorraine; Tremblay, Cécile; Triant, Virginia Jeanne; Tribble, Marc; Trinh, P.; Tuscher, Susan; Vaccaro, Anthony J.; Valadas, Emilia; Vecino, Isabel; Wagner, Theresa; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas; Warner, Daniel; Watson, Terry; Weber, Karl; Weber, Terry; Webster, Duncan; Weinberg, Winkler; Weintrob, Amy; Weis, Steve; Wenger, Scott; Werntz, Gary; Wheeler, David; White, David; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford; Wolf, Eva; Wright, David; Yang, Otto; Yawetz, Sigal; Yurdin, David L.; Zabukovic, Brandon; Zachary, Kimon; Zeeman, Beth; Baker, Brett; Block, Brian; Braaten, Conrad; Darrah, Aisha Tiala; LaTour, Brooke; Lian, Jeffrey; McClurg, Cheryl; Piechocka-Trocha, Alicja; Proudfoot, Jacqueline; Rothchild, Alissa; Toth, Ildiko; Barefoot, Laurie; Bazner, Suzane; Cutrell, Emily; Johnston, Mary; Lemay, Paul; Moss, Kristin; Oladehin, Olakunle; Rosenberg, Rachel; Tinsley, Jake; Tsao, Alice; Addo, Marylyn; Allen, Todd; Alter, Galit; Altfeld, Marcus; Legall, Sylvie; Walker, Bruce; Yu, Xu; Burtt, Noël; Carmago, Amy; Crawford, Gabriel; Crenshaw, Andrew; Davies, Leela; Gabriel, Stacey; Gianniny, Lauren; Guiducci, Candace; Brumme, Chanson; de Bakker, Paul; Jia, Xiaoming; McLaren, Paul; Haas, David; Kuritzkes, Daniel; Gulick, Roy; Ribaudo, Heather; Deeks, Steve; Henn, Matthew; Le Gall, Sylvie; Heckerman, David

    2010-01-01

    Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We

  12. Plasma drug concentrations and virologic evaluations after stopping treatment with nonnucleoside reverse-transcriptase inhibitors in HIV type 1-infected children.

    NARCIS (Netherlands)

    Cressey, T.R.; Green, H.; Khoo, S.; Treluyer, J.M.; Compagnucci, A.; Saidi, Y.; Lallemant, M.; Gibb, D.M.; Burger, D.M.

    2008-01-01

    BACKGROUND: The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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 ( ...

  3. 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 ...

  4. New subtypes and genetic recombination in HIV type 1-infecting patients with highly active antiretroviral therapy in Peru (2008-2010).

    Science.gov (United States)

    Yabar, Carlos Augusto; Acuña, Maribel; Gazzo, Cecilia; Salinas, Gabriela; Cárdenas, Fanny; Valverde, Ada; Romero, Soledad

    2012-12-01

    HIV-1 subtype B is the most frequent strain in Peru. However, there is no available data about the genetic diversity of HIV-infected patients receiving highly active antiretroviral therapy (HAART) here. A group of 267 patients in the Peruvian National Treatment Program with virologic failure were tested for genotypic evidence of HIV drug resistance at the Instituto Nacional de Salud (INS) of Peru between March 2008 and December 2010. Viral RNA was extracted from plasma and the segments of the protease (PR) and reverse transcriptase (RT) genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), purified, and fully sequenced. Consensus sequences were submitted to the HIVdb Genotypic Resistance Interpretation Algorithm Database from Stanford University, and then aligned using Clustal X v.2.0 to generate a phylogenetic tree using the maximum likelihood method. Intrasubtype and intersubtype recombination analyses were performed using the SCUEAL program (Subtype Classification by Evolutionary ALgo-rithms). A total of 245 samples (91%) were successfully genotyped. The analysis obtained from the HIVdb program showed 81.5% resistance cases (n=198). The phylogenetic analysis revealed that subtype B was predominant in the population (98.8%), except for new cases of A, C, and H subtypes (n=4). Of these cases, only subtype C was imported. Likewise, recombination analysis revealed nine intersubtype and 20 intrasubtype recombinant cases. This is the first report of the presence of HIV-1 subtypes C and H in Peru. The introduction of new subtypes and circulating recombinants forms can make it difficult to distinguish resistance profiles in patients and consequently affect future treatment strategies against HIV in this country.

  5. The necrosis-avid small molecule HQ4-DTPA as a multimodal imaging agent for monitoring radiation therapy-induced tumor cell death

    NARCIS (Netherlands)

    M.A. Stammes (Marieke A.); Maeda, A. (Azusa); Bu, J. (Jiachuan); Scolard, D.A. (Deborah A.); Kulbatski, I. (Iris); Medeiros, P.J. (Philip J.); Sinisi, R. (Riccardo); Dubikovskaya, E.A. (Elena A.); T.J.A. Snoeks (thomas); E.R. van Beek (Ermond); A. Chan (Albert); C.W.G.M. Löwik (Clemens); DaCosta, R.S. (Ralph S.)

    2016-01-01

    textabstractPurpose: Most effective antitumor therapies induce tumor cell death. Non-invasive, rapid and accurate quantitative imaging of cell death is essential for monitoring early response to antitumor therapies. To facilitate this, we previously developed a biocompatible necrosis-avid

  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. 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 ). ...

  8. Conserved molecular signatures in gp120 are associated with the genetic bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency virus (SHIV), and HIV type 1 (HIV-1) transmission.

    Science.gov (United States)

    Gonzalez, Mileidy W; DeVico, Anthony L; Lewis, George K; Spouge, John L

    2015-04-01

    Human immunodeficiency virus (HIV) transmission typically results from infection by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly at random from the donor pool, or are they selected based on advantageous traits facilitating transmission? Finding evidence for selection during transmission is of particular interest, because it would indicate that phenotypic and/or genetic properties of the viruses might be harnessed as potential vaccine targets or immunotherapies. Here, we systematically evaluated the differences between the Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F variants in search of "signature" sites of transmission. We also surveyed residue preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed significant selection, and an additional two sites showed a similar trend. Therefore, the six sites clearly differentiate T/F viruses from the majority of circulating variants in the stocks. The selection of SIV/SHIV could be inferred reasonably across both vaccinated and unvaccinated subjects, with infections resulting from vaginal, rectal, and intravenous routes of transmission and regardless of viral dosage. The evidence for selection in SIV and SHIV T/F variants is strong and plentiful, and in HIV the evidence is suggestive though commensurate with the availability of suitable data for analysis. Two of the signature residues are completely conserved across the SIV, SHIV, and HIV variants we examined. Five of the signature residues map to the C1 region of gp120 and one to the signal peptide. Our data raise the possibility that C1, while governing the association between gp120 and gp41, modulates transmission efficiency, replicative fitness, and/or host cell tropism at the level of virus-cell attachment and entry. The present study finds significant evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data provide ancillary evidence suggesting the same sites

  9. 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 ...

  10. 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 ...

  11. 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] ...

  12. Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia.

    Science.gov (United States)

    El Hajj, Hiba; El-Sabban, Marwan; Hasegawa, Hideki; Zaatari, Ghazi; Ablain, Julien; Saab, Shahrazad T; Janin, Anne; Mahfouz, Rami; Nasr, Rihab; Kfoury, Youmna; Nicot, Christophe; Hermine, Olivier; Hall, William; de Thé, Hugues; Bazarbachi, Ali

    2010-12-20

    Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As(2)O(3) and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients.

  13. Molecular typing of the recently expanding subtype B HIV-1 epidemic in Romania: evidence for local spread among MSMs in Bucharest area.

    Science.gov (United States)

    Paraschiv, Simona; Otelea, Dan; Batan, Ionelia; Baicus, Cristian; Magiorkinis, Gkikas; Paraskevis, Dimitrios

    2012-07-01

    HIV-1 subtype B is predominant in Europe except in some countries from Eastern Europe which are characterized by a high prevalence of non-B subtypes and circulating recombinant forms (CRFs). Romania is a particular case: the HIV-1 epidemic started with subtype F1 which is still the most prevalent. Previous studies have shown an increasing prevalence of subtype B which is the second most frequent one among the newly diagnosed individuals, followed by subtype C and several CRFs as well as unique recombinant forms (URFs). Our objective was to analyze in detail the characteristics (way of dispersal, association with transmission risk groups) of the subtype B infections in Romania by means of phylogenetic analysis. Among all the individuals sampled during 2003-2010, 71 out of 1127 patients (6.3%) have been identified to be infected with subtype B strains. The most frequent route of infection identified in HIV-1 subtype B patients in Romania was MSM transmission (39.6%), followed by the heterosexual route (35.2%). Many of the patients acquired the infection abroad, mainly in Western European countries. Phylogenetic analysis indicated the existence of a local transmission network (monophyletic clade) including 14 patients, mainly MSM living in the Bucharest area. We estimate the origin of the local transmission network that dates at the beginning of the 90s; the introduction of the F1 and C subtypes occurred earlier. The rest of the sequences were intermixed with reference strains sampled across Europe suggesting that single infection were not followed by subsequent dispersal within the local population. Although HIV-1 subtype B epidemic in Romania is recent, there is evidence for local spread among the MSMs, in addition to multiple introductions. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Human Leukocyte Antigen (HLA Class I Down-Regulation by Human Immunodeficiency Virus Type 1 Negative Factor (HIV-1 Nef: What Might We Learn From Natural Sequence Variants?

    Directory of Open Access Journals (Sweden)

    Philip Mwimanzi

    2012-09-01

    Full Text Available HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS. Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by antiviral CD8+ T lymphocytes. Extensive research has been conducted on Nef to determine protein domains that are required for its immune evasion activities and to identify critical cellular co-factors, and our mechanistic understanding of this process is becoming more complete. This review highlights our current knowledge of Nef-mediated HLA class I down-regulation and places this work in the context of naturally occurring sequence variation in this protein. We argue that efforts to fully understand the critical role of Nef for HIV-1 pathogenesis will require greater analysis of patient-derived sequences to elucidate subtle differences in immune evasion activity that may alter clinical outcome.

  15. HIV-2 and its neurological manifestations | Rolfe | South African ...

    African Journals Online (AJOL)

    The human immunodeficiency virus type 2 (HIV-2) produces a similar spectrum of illness as HIV-1, including AIDS, and is clinically indistinguishable. There is evidence that it is less pathogenic, with a longer natural history. HIV2 infection is endemic in West Africa, especially in the former Portuguese and French colonies.

  16. HIV-1 vaccine design: Learning from natural infection

    NARCIS (Netherlands)

    van den Kerkhof, T.L.G.M.

    2016-01-01

    Het humane immuundeficiëntie virus type 1 (hiv-1) is het virus dat aids veroorzaakt. Er is nog steeds geen bescherming tegen een hiv-1 infectie en de beëindiging van de wereldwijde epidemie kan waarschijnlijk alleen worden bereikt met behulp van een vaccin. Een hiv-1 vaccin zal bescherming moeten

  17. My secret: The social meaning of HIV/AIDS stigma

    African Journals Online (AJOL)

    N. Judgeo

    2014-07-01

    Jul 1, 2014 ... Brown, Trujillo and Macintyre (2001) believed that the type and magnitude of people's reactions to this epidemic is largely due to HIV/AIDS stigma. HIV stigma remains the roadblock to a concerted action to reduce the transmission of HIV as it impedes prevention and treatment efforts (Campbell, Foulis, ...

  18. 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

    gender-specific facilitators of HIV testing. Findings suggest a number of avenues for increasing HIV testing rates including increasing the number and types of settings offering high-quality HIV testing; promoting STI as well as HIV testing; better integrating STI and HIV testing systems; implementing peer-driven social/behavioral intervention approaches to harness the positive influence of social networks and reduce unfavorable shared peer norms; and specialized approaches for women who use drugs.

  19. Comparative evaluation of photodynamic therapy induced by two different photosensitizers in rat experimental candidiasis

    Directory of Open Access Journals (Sweden)

    Heidar Khademi

    2014-01-01

    Full Text Available Background: Antimicrobial efficacy of photodynamic therapy (PDT depends on both the photosensitizer (PS and laser parameters. In the present study, antimicrobial effectiveness of PDT with different concentrations of two PSs was compared. Materials and Methods: In this study, we employed fifty-nine 6-week-old male Wistar rats. All except the negative and overall control groups were immunosuppressed and then orally inoculated with a suspension of Candida albicans (9 × 10 8 CFU/ml. At 4 days after oral inoculation, swabbing of tongue dorsum was performed to recover yeast from the tongue before treatment; on the next day, PDT was carried out on tongue dorsums by use of different concentrations of methylene blue (MB or poly-L-lysine-chlorine (e6 conjugate (pL-ce6 as PS; followed by a 10 min diode laser illumination at 660 nm (n = 6 each. Then, sampling was again performed. The difference between yeast recovery before and after treatment was compared between the groups by one-way analysis of variance test (α = 0.05. After sacrificing the animals, their tongues were surgically removed and processed for histological evaluation of the presence of yeast and tissue reaction. Results: PDT mediated by both PSs, regardless of the type and their concentration, resulted in a significant microbiological and histological reduction in C. albicans counts in comparison with positive control group (P < 0.001. There was no difference in epithelial lesions and inflammatory responses between groups. Conclusion: PDT mediated MB or pL-ce6 is a promising approach for treatment of oral candidiasis.

  20. Differentiating therapy-induced leukoencephalopathy from unmyelinated white matter in children treated for acute lymphoblastic leukemia (ALL)

    Science.gov (United States)

    Reddick, Wilburn E.; Glass, John O.; Pui, Ching-Hon

    2003-05-01

    Reliably detecting subtle therapy-induced leukoencephalopathy in children treated for cancer is a challenging task due to its nearly identical MR properties and location with unmyelinated white matter. T1, T2, PD, and FLAIR images were collected for 44 children aged 1.7-18.7 (median 5.9) years near the start of therapy for ALL. The ICBM atlas and corresponding apriori maps were spatially normalized to each patient and resliced using SPM99 software. A combined imaging set consisting of MR images and WM, GM and CSF apriori maps were then analyzed with a Kohonen Self-Organizing Map. Vectors from hyperintense regions were compared to normal appearing genu vectors from the same patient. Analysis of the distributions of the differences, calculated on T2 and FLAIR images, revealed two distinct groups. The first large group, assumed normal unmyelinated white matter, consisted of 37 patients with changes in FLAIR ranging from 80 to 147 (mean 117-/+17) and T2 ranging from 92 to 217 (mean 144-/+28). The second group, assumed leukoencephalopathy, consisted of seven patients with changes in FLAIR ranging from 154 to 196 (mean 171-/+19) and T2 ranging from 190 to 287 (mean 216-/+33). A threshold was established for both FLAIR (change > 150) and T2 (change > 180).

  1. eHealth interventions for HIV prevention.

    Science.gov (United States)

    Noar, Seth M; Willoughby, Jessica Fitts

    2012-01-01

    The rapidly changing media landscape and proliferation of new technologies creates vast new opportunities for HIV prevention. The fast growth of the relatively new eHealth field is a testament to the excitement and promise of these new technologies. eHealth interventions in HIV prevention tested to date include computer- and Internet-based interventions; chat room interventions; text messaging interventions; and social media. The current article provides a brief review of these types of interventions in HIV prevention, including their unique advantages and evidence of efficacy. Implications for future research in the eHealth HIV prevention field are discussed.

  2. Stroke in a Patient With HIV Infection

    Directory of Open Access Journals (Sweden)

    Buse Rahime Hasırcı

    2015-08-01

    Full Text Available Stroke which is a common complication in Human immumodeficiency virus type 1 positive patients is seen between 1% and 5% in clinical series. Vasculopathy and atherogenesis in HIV are the main pathologic mechanisms of stroke. We report a 63 year old man with sudden onset of a right hemiplegia and who was diagnosed as HIV-related stroke.

  3. Clinical research in HIV-1 infected children

    NARCIS (Netherlands)

    P.L.A. Fraaij (Pieter)

    2005-01-01

    textabstractAcquired immune deficiency syndrome (AIDS) was described for the first time in 1981. Two years later the previously unknown human immunodeficiency virus (HIV) was identified as the causative agent. HIV has been included in the genus Lent/viruses of the Retroviridae family. Two types are

  4. Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells.

    Science.gov (United States)

    Dos Santos, Ancély F; Terra, Letícia F; Wailemann, Rosangela A M; Oliveira, Talita C; Gomes, Vinícius de Morais; Mineiro, Marcela Franco; Meotti, Flávia Carla; Bruni-Cardoso, Alexandre; Baptista, Maurício S; Labriola, Leticia

    2017-03-15

    -PDT as a highly efficient strategy which could use as a powerful adjunct therapy to surgery of breast tumours, and possibly other types of tumours, to safely increase the eradication rate of microscopic residual disease and thus minimizing the chance of both local and metastatic recurrence.

  5. Untangling the Gordian knot of HIV, stress, and cognitive impairment

    OpenAIRE

    Valdez, Arielle N.; Rubin, Leah H.; Neigh, Gretchen N.

    2016-01-01

    As individuals live longer with HIV, this ?graying of the HIV epidemic? has introduced a new set of challenges including a growing number of age and inflammation-related diseases such as cardiovascular disease, type II diabetes, cancer, and dementia. The biological underpinnings of these complex and co-morbid diseases are not fully understood and become very difficult to disentangle in the context of HIV and aging. In the current review we examine the contributions and interactions of HIV, st...

  6. Hearing Loss in HIV-Infected Children in Lilongwe, Malawi.

    OpenAIRE

    Hrapcak, S; Kuper, H; Bartlett, P.; Devendra, A; Makawa, A; Kim, M; Kazembe, P.; Ahmed, S.

    2016-01-01

    Introduction With improved access to antiretroviral therapy (ART), HIV infection is becoming a chronic illness. Preliminary data suggest that HIV-infected children have a higher risk of disabilities, including hearing impairment, although data are sparse. This study aimed to estimate the prevalence and types of hearing loss in HIV-infected children in Lilongwe, Malawi. Methods This was a cross-sectional survey of 380 HIV-infected children aged 4?14 years attending ART clinic in Lilongwe betwe...

  7. Quantification of the Epitope Diversity of HIV-1-Specific Binding Antibodies by Peptide Microarrays for Global HIV-1 Vaccine Development

    OpenAIRE

    Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Korber, Bette T; Barouch, Dan H.

    2014-01-01

    An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6,564 peptides from across...

  8. Four years of natural history of HIV-1 infection in African women : a prospective cohort study in Kigali (Rwanda), 1988-1993

    OpenAIRE

    Leroy, V.; Msellati, Philippe; Lepage, P.; Batungwanayo, J.; Hitimana, D.G.; Taelman, H.; Bogaerts, J.; Boineau, F.; Van de Perre, P.; Simonon, A.; Salamon, R.; Dabis, F.

    1995-01-01

    Clinical features and mortality due to human immunodeficiency virus type-1 (HIV-1) infection in women are described as part of a prospective 4-year cohort study on perinatal transmission of HIV in Kigali, Rwanda. Two hundred fifteen HIV-positive (HIV+) and 216 HIV-negative (HIV-) pregnant women were enrolled at delivery between November 1988 and June 1989. Clinical information collected during systematic quarterly examinations was compared. HIV antibody tests were performed at delivery and CD...

  9. Short communication: Evidences of recent decline in the expansion rate of the HIV type 1 subtype C and CRF31_BC epidemics in southern Brazil.

    Science.gov (United States)

    Bello, Gonzalo; Guimarães, Monick L; Passaes, Caroline P B; Matos Almeida, Sabrina E; Veloso, Valdilea G; Morgado, Mariza G

    2009-11-01

    The HIV-1 epidemic in southern Brazil is characterized by the high prevalence of subtype C and CRF31_BC infections but little is known about the population dynamics of these strains over time. We used a total of 82 env and 72 pol HIV-1 subtype C sequences collected from 1991 to 2006 and 47 pol CRF31_BC sequences collected from 1998 to 2006 from Brazilian patients to reconstruct the demographic history of these HIV-1 strains. Estimations of demographic history were performed using a Bayesian Markov Chain Monte Carlo coalescent-based approach as implemented in the BEAST program. Our analyses indicate that subtype C and CRF31_BC epidemics experienced an initial period of fast exponential spread in the southern Brazilian population during the 1980s and early 1990s, but the spreading rate of these epidemics seems to have slowed down since the middle 1990s. The initial mean exponential growth rate of the subtype C epidemic was estimated to be around 0.70-0.90/year, whereas the estimated population growth rate of CRF31_BC was 1.3/year, more than two times higher than that previously described for this CRF. These results suggest for the first time that the growth rate of subtype C and CRF31_BC epidemics has been changing over time in southern Brazil with evidence for a deceleration in recent years. During the expansion phase, the CRF31_BC seems to have spread at a rate much higher than Brazilian parental subtypes B and C.

  10. Transmitted drug resistance among antiretroviral-naive patients with established HIV type 1 infection in Santo Domingo, Dominican Republic and review of the Latin American and Caribbean literature.

    Science.gov (United States)

    Myers, Julie E; Taylor, Barbara S; Rojas Fermín, Rita A; Reyes, Emily Virginia; Vaughan, Catherine; José, Lina; Javier, Carmen; Franco Estévez, Ramona; Donastorg Cabral, Yeycy; Batista, Arelis; Lie, Yolanda; Coakley, Eoin; Hammer, Scott M; Brudney, Karen

    2012-07-01

    Emergence of HIV resistance is a concerning consequence of global scale-up of antiretroviral therapy (ART). To date, there is no published information about HIV resistance from the Dominican Republic. The study's aim was to determine the prevalence of transmitted drug resistance (TDR) to reverse transcriptase and protease inhibitors in a sample of chronically HIV-1-infected patients in one clinic in Santo Domingo. The data are presented in the context of a review of the TDR literature from Latin America and the Caribbean. Genotype testing was successfully performed on 103 treatment-naive adults planning to initiate antiretroviral therapy; the World Health Organization (WHO) list of surveillance drug resistance mutations (SDRM) was used to determine the presence of TDR mutations. WHO SDRM were identified in eight patients (7.8%); none had received sdNVP. There were no significant differences in epidemiologic or clinical variables between those with or without WHO SDRM. The prevalence of WHO SDRM was 1.0% and 6.8% for nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. No WHO SDRMs for protease inhibitors were identified. Among 12 studies of TDR in the region with a sample size of at least 100 subjects, the reported prevalence of SDRM ranged from 2.8% to 8.1%. The most commonly identified SDRM was K103N. This information adds to our understanding of the epidemiology of TDR in the region and the possible role such mutations could play in undermining first-line treatment. Ongoing surveillance is clearly needed to better understand the TDR phenomenon in the Caribbean.

  11. Short communication: Severe symptomatic hyperlactatemia among HIV type 1-infected adults on antiretroviral therapy in Côte d'Ivoire.

    Science.gov (United States)

    Minga, Albert; Lewden, Charlotte; Dohoun, Lambert; Abo, Yao; Emieme, Arlette; Coulibaly, Ali; Salamon, Roger; Eholié, Serge; Anglaret, Xavier; Danel, Christine

    2010-09-01

    Stavudine is no longer recommended for use in first-line antiretroviral therapy (ART), but it remains in high demand worldwide because it is affordable. We report the clinical presentation and incidence of severe hyperlactatemia (SL) in HIV-infected adults who initiated ART between April 2005 and May 2009 in Côte d'Ivoire, West Africa. In a prospective cohort study at the HIV care center affiliated with the National Centre for Blood Transfusion, we used standardized forms to record baseline and follow-up data. We measured serum lactate levels for all adults on ART who showed signs of hyperlactatemia. SL was defined as serum lactate >2.5 mmol/liter. Overall, 806 adults initiated ART. Among the 591 patients (73%) on stavudine-containing regimens, 394 were women (67%); the median pre-ART CD4 count was 150/mm3 and the median body mass index was 20.9 kg/m2. These patients were followed for a median of 28 months. We detected SL only among patients taking stavudine. The incidence of SL was 0.55/100 person-years (PY) (95% CI 0.47-0.63) overall and 0.85/100 PY among women (95% CI 0.75-0.95). Among the eight patients with SL, 100% lost >9% of body weight before diagnosis, 100% had serum lactate >4 mmol/liter (range 4.2-12.1), 50% had pre-ART BMI >25 kg/m2, and three patients died (38%), accounting for 6.4% of deaths among patients taking stavudine. As long as HIV clinicians continue to use stavudine in sub-Saharan Africa, they should watch out for acute unexplained weight loss in patients taking ART, particularly among women and patients with high pre-ART BMI.

  12. Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3-<36 months

    DEFF Research Database (Denmark)

    NN, NN; Valerius, Niels Henrik

    2010-01-01

    the plasma concentration-time curve over 24 h (AUC(0-24)) and the maximum concentration (C(max)) were compared using geometric mean ratios (GMRs); 90% confidence intervals (CIs) within the range of 0.80-1.25 were considered bioequivalent. RESULTS: A total of 18 children (4, 6 and 8 in the 3-...-daily dosing: abacavir and lamivudine GMRs were 2.04 (90% CI 1.73-2.42) and 1.78 (90% CI 1.52-2.09), respectively. At baseline, 12, 24 and 48 weeks, 89%, 94%, 100% and 89% of children had HIV-1 RNABioequivalence was demonstrated on AUC(0-24) between twice...

  13. Human TRIM5α mediated restriction of different HIV-1 subtypes and Lv2 sensitive and insensitive HIV-2 variants

    Directory of Open Access Journals (Sweden)

    Hagmann Isabel

    2006-11-01

    Full Text Available Abstract In order to characterize the antiviral activity of human TRIM5α in more detail human derived indicator cell lines over expressing wild type human TRIM5α were generated and challenged with HIV-1 and HIV-2 viruses pseudotyped with HIV envelope proteins in comparison to VSV-G pseudotyped particles. HIV envelope protein pseudotyped particles (HIV-1[NL4.3], HIV-1[BaL] showed a similar restriction to infection (12 fold inhibition compared to VSV-G pseudotyped viruses after challenging TZM-huTRIM5α cells. For HIV-2 a stronger restriction to infection was observed when the homologous envelope protein Env42S was pseudotyped onto these particles compared to VSV-G pseudotyped HIV-2 particles (8.6 fold inhibition versus 3.4 fold inhibition. It has been shown that HIV-2 is restricted by the restriction factor Lv2, acting on capsid like TRIM5α. A mutation of amino acid 73 (I73V of HIV-2 capsid renders this virus Lv2-insensitive. Lv2-insensitive VSV-G pseudotyped HIV-2/I73V particles showed a similar restriction to infection as did HIV-2[VSV-G] particles (4 fold inhibition. HIV-2 envelope protein (Env42S-pseudotyped HIV-2/I73V particles revealed a 9.3 fold increase in infection in TZM cells but remained restricted in TZM-huTRIM5α cells (80.6 fold inhibition clearly indicating that at least two restriction factors, TRIM5α and Lv2, act on incoming HIV-2 particles. Further challenge experiments using primary isolates from different HIV-1 subtypes and from HIV-1 group O showed that wild type human TRIM5α restricted infection independent of coreceptor use of the infecting particle but to variable degrees (between 1.2 and 19.6 fold restriction.

  14. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus–Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L.; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S.; Cox, Josephine H.

    2017-01-01

    Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35–vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH). Results. All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot–determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic. Conclusions. SeV-Gag primed functional, durable HIV-specific T

  15. HIV type 1 V3 domain serotyping and genotyping in Gauteng, Mpumalanga, KwaZulu-Natal, and Western Cape Provinces of South Africa.

    Science.gov (United States)

    Engelbrecht, S; Smith, T L; Kasper, P; Faatz, E; Zeier, M; Moodley, D; Clay, C G; van Rensburg, E J

    1999-03-01

    More than 20.8 million people are living with HIV/AIDS in sub-Saharan Africa, with southern Africa the worst affected area and accounting for one of the fastest growing AIDS epidemics worldwide. Samples from 81 patients, including 25 from KwaZulu-Natal, 26 from Gauteng, 5 from Mpumalanga, and 25 from Western Cape Province, were serotyped using a competitive V3 peptide enzyme immunoassay (cPEIA). Viral RNA was also isolated from serum and the V3 region amplified by reverse transcriptase polymerase chain reaction (RT-PCR) to obtain a 240-bp product for direct sequencing of 29 samples. CLUSTAL W was used to make multiple sequence alignments. Distance calculation, tree construction methods, and bootstrap analysis were done using TREECON. Subtype C-like V3 loop sequences predominate in all provinces tested in South Africa. Discordant sero- and genotype results were observed in one patient only. The correlation between sero- and genotyping was 96% (24 of 25) in KwaZulu-Natal and 100% in Gauteng and Mpumalanga. In Western Cape Province 18% of patients were identified as sero/genotype B and 82% as sero/genotype C. Our data show that results of the second-generation V3 cPEIA correlated well with V3 sequencing and would be a rapid and affordable screening test to monitor the explosive southern African HIV-1 epidemic.

  16. The predominance of Human Immunodeficiency Virus type 1 (HIV-1 circulating recombinant form 02 (CRF02_AG in West Central Africa may be related to its replicative fitness

    Directory of Open Access Journals (Sweden)

    Butel Christelle

    2006-07-01

    Full Text Available Abstract Background CRF02_AG is the predominant HIV strain circulating in West and West Central Africa. The aim of this study was to test whether this predominance is associated with a higher in vitro replicative fitness relative to parental subtype A and G viruses. Primary HIV-1 isolates (10 CRF02_AG, 5 subtype A and 5 subtype G were obtained from a well-described Cameroonian cohort. Growth competition experiments were carried out at equal multiplicity of infection in activated T cells and monocyte-derived dendritic cells (MO-DC in parallel. Results Dual infection/competition experiments in activated T cells clearly indicated that CRF02_AG isolates had a significant replication advantage over the subtype A and subtype G viruses. The higher fitness of CRF02_AG was evident for isolates from patients with CD4+ T cell counts >200 cells/μL (non-AIDS or CD4+ T cell counts Conclusion We observed a higher ex vivo replicative fitness of CRF02_AG isolates compared to subtype A and G viruses from the same geographic region and showed that this was independent of the co-receptor tropism and irrespective of high or low CD4+ T cell count. This advantage in replicative fitness may contribute to the dominant spread of CRF02_AG over A and G subtypes in West and West Central Africa.

  17. Detection of Hepatitis B Virus (HBV) Genomes and HBV Drug Resistant Variants by Deep Sequencing Analysis of HBV Genomes in Immune Cell Subsets of HBV Mono-Infected and/or Human Immunodeficiency Virus Type-1 (HIV-1) and HBV Co-Infected Individuals

    Science.gov (United States)

    Lee, Z.; Nishikawa, S.; Gao, S.; Eksteen, J. B.; Czub, M.; Gill, M. J.; Osiowy, C.; van der Meer, F.; van Marle, G.; Coffin, C. S.

    2015-01-01

    The hepatitis B virus (HBV) and the human immunodeficiency virus type 1 (HIV-1) can infect cells of the lymphatic system. It is unknown whether HIV-1 co-infection impacts infection of peripheral blood mononuclear cell (PBMC) subsets by the HBV. Aims To compare the detection of HBV genomes and HBV sequences in unsorted PBMCs and subsets (i.e., CD4+ T, CD8+ T, CD14+ monocytes, CD19+ B, CD56+ NK cells) in HBV mono-infected vs. HBV/HIV-1 co-infected individuals. Methods Total PBMC and subsets isolated from 14 HBV mono-infected (4/14 before and after anti-HBV therapy) and 6 HBV/HIV-1 co-infected individuals (5/6 consistently on dual active anti-HBV/HIV therapy) were tested for HBV genomes, including replication indicative HBV covalently closed circular (ccc)-DNA, by nested PCR/nucleic hybridization and/or quantitative PCR. In CD4+, and/or CD56+ subsets from two HBV monoinfected cases, the HBV polymerase/overlapping surface region was analyzed by next generation sequencing. Results All analyzed whole PBMC from HBV monoinfected and HBV/HIV coinfected individuals were HBV genome positive. Similarly, HBV DNA was detected in all target PBMC subsets regardless of antiviral therapy, but was absent from the CD4+ T cell subset from all HBV/HIV-1 positive cases (PHBV monoinfected cases on tenofovir therapy, mutations at residues associated with drug resistance and/or immune escape (i.e., G145R) were detected in a minor percentage of the population. Summary HBV genomes and drug resistant variants were detectable in PBMC subsets from HBV mono-infected individuals. The HBV replicates in PBMC subsets of HBV/HIV-1 patients except the CD4+ T cell subpopulation. PMID:26390290

  18. 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, ...

  19. 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 ( ...

  20. Lectins with Anti-HIV Activity: A Review

    Directory of Open Access Journals (Sweden)

    Ouafae Akkouh

    2015-01-01

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

  1. 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 ...

  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. HIV-1 Latency in Monocytes/Macrophages

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

  5. Human immunodeficiency virus type 1 (HIV-1 reservoirs: mechanisms of latency and therapeutic strategies = Reservorios del virus de inmunodeficiencia humana tipo 1 (VIH-1: mecanismos de latencia y estrategias terapéuticas

    Directory of Open Access Journals (Sweden)

    Arcia Anaya, Eliuth David

    2014-07-01

    Full Text Available The human immunodeficiency virus type 1 can establish a latent infection in different kind of cells, which constitute the cellular reservoirs for the virus and allow its maintenance in the body indefinitely, even in patients with antiretroviral treatment. The main reservoirs of the HIV-1 are resting CD4+ T cells, although cells like monocytes/macrophages, dendritic cells, and other cells like hematopoietic stem cells and mast cells may be reservoirs of the virus. There are different mechanisms that contribute to the establishment and maintenance of latency in those cells, and include transcriptional interference, low availability of transcription factors, chromatin condensation, some microRNA that block viral translation, and so on. The knowledge of these mechanisms is crucial for the development of new drugs that may eliminate the virus from the body and lead to a cure.

  6. Identification of a novel binding site between HIV type 1 Nef C-terminal flexible loop and AP2 required for Nef-mediated CD4 downregulation.

    Science.gov (United States)

    Jin, Yong-Jiu; Cai, Catherine Yi; Mezei, Mihaly; Ohlmeyer, Michael; Sanchez, Roberto; Burakoff, Steven J

    2013-04-01

    HIV-1 Nef is an accessory protein necessary for HIV-1 virulence and rapid AIDS development. Nef promotes viral replication and infection by connecting CD4 and several other cell surface receptors to the clathrin adaptor protein AP2, resulting in the internalization and degradation of the receptors interacting with Nef. We investigated how Nef can mediate constitutive receptor endocytosis through the interaction of the dileucine motif in its C-terminal flexible loop (C-loop) with AP2, whereas AP2 binding of the transmembrane receptors usually results in an equilibrated (recycled) endocytosis. Our results indicated that in addition to the dileucine motif, there is a second motif in the Nef C-loop involved in the Nef-AP2 interaction. Nef-mediated CD4 downregulation was impaired when the residue in the hydrophobic region in the Nef C-loop (LL165HPMSLHGM173) was mutated to a basic residue K/R or an acidic residue E/D or to the rigid residue P, or when M168L170, L170H171, or G172M173 was mutated to AA. A pull-down assay indicated that AP2 was not coprecipitated with Nef mutants that did not downregulate CD4. Molecular modeling of the Nef C-terminal flexible loop in complex with AP2 suggests that M168L170 occupies a pocket in the AP2 σ2 subunit. Our data suggest a new model in the Nef-AP2 interaction in which the hydrophobic region in the Nef C-loop with the dileucine (L164L165) motif and M168L170 motif binds to AP2(σ2), while the acidic motif E174 and D175 binds to AP2(α), which explains how Nef through the flexible loop connects CD4 to AP2 for constitutive CD4 downregulation.

  7. Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice.

    Directory of Open Access Journals (Sweden)

    Guangming Li

    2014-07-01

    Full Text Available The role of plasmacytoid dendritic cells (pDC in human immunodeficiency virus type 1 (HIV-1 infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment.

  8. CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection

    DEFF Research Database (Denmark)

    Buggert, Marcus; Frederiksen, Juliet Wairimu; Lund, Ole

    2016-01-01

    , senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T cell subpopulations linked to infection type and disease stage. RESULTS: HIV-2-infected individuals had early- and late-differentiated CD4+ T cell...... cells are linked to such outcome. DESIGN: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion...... clusters with lower activation (CD38+HLA-DR+) and exhaustion (PD-1) than HIV-1 and HIV-D-infected subjects. We also noted that aviremic HIV-2-infected individuals possessed fewer CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegatives, aviremic HIV-2...

  9. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... people with AIDS often develop infections of the lungs, brain, eyes, and other organs, and they frequently suffer dangerous weight loss, diarrhea, and a type of cancer called Kaposi's sarcoma. 1 Some hopeful news is that, in recent years, HIV is no longer ...

  10. Subtype Classification of Iranian HIV-1 Sequences Registered in the HIV Databases, 2006-2013

    Science.gov (United States)

    Baesi, Kazem; Moallemi, Samaneh; Farrokhi, Molood; Alinaghi, Seyed Ahmad Seyed; Truong, Hong–Ha M.

    2014-01-01

    Background The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. Methods All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods. Results A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. Conclusions Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies. PMID:25188443

  11. Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013.

    Directory of Open Access Journals (Sweden)

    Kazem Baesi

    Full Text Available BACKGROUND: The rate of human immunodeficiency virus type 1 (HIV-1 infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. METHODS: All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ and Maximum Parsimony methods. RESULTS: A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. CONCLUSIONS: Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.

  12. Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

    Science.gov (United States)

    Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George; Sloan, Derek D; Murry, Jeffrey P

    2017-04-15

    Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently

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

    Directory of Open Access Journals (Sweden)

    Xinli Lu

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

  14. HIV seroprevalence in Oklahoma childbearing women.

    Science.gov (United States)

    Govin, M; Botchlet, R; Graves, T; Harkess, J; Kudlac, J

    1991-11-01

    From October 1989 through September 1990, we conducted an unlinked seroprevalence survey in Oklahoma to determine the prevalence of human immunodeficiency virus, type 1 (HIV) in women at the time of childbirth. Blood specimens obtained from 41,809 newborns in conjunction with the state's newborn metabolic screening program were tested for HIV after personal identifiers were removed. The overall HIV seroprevalence rate was 0.02% (10/41,809). Rates were highest for mothers aged 30 to 39 years (0.06%, 3/5,158). No difference was found between the HIV seroprevalence rates for women residing in standard metropolitan areas (MSAs) of the state (0.03%, 6/21,105) and women residing in non-metropolitan areas (0.03%, 3/11,904). When compared to other states where surveys have been done, Oklahoma's rate of HIV infection in childbearing women was low.

  15. Stoichiometric parameters of HIV-1 entry.

    Science.gov (United States)

    Zarr, Melissa; Siliciano, Robert

    2015-01-01

    During HIV type 1 (HIV-1) entry, trimers of gp120 bind to CD4 and either the CCR5 or CXCR4 coreceptor on the target cell. The stoichiometric parameters associated with HIV-1 entry remain unclear. Important unanswered questions include: how many trimers must attach to CD4 molecules, how many must bind coreceptors, and how many functional gp120 subunits per trimer are required for entry? We performed single round infectivity assays with chimeric viruses and compared the experimental relative infectivity curves with curves generated by mathematical models. Our results indicate that HIV-1 entry requires only a small number of functional spikes (one or two), that Env trimers may function with fewer than three active subunits, and that there is no major difference in the stoichiometric requirements for CCR5 vs. CXCR4 mediated HIV-1 entry into host cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. A Survey of Plants with Anti-HIV Active Compounds and their Modes ...

    African Journals Online (AJOL)

    Administrator

    cellular fusion and syncytium formation. 18. Annonaceae. Polyalthia suberosa. Lanostane-type triterpene, suberosol. Anti-HIV replication activity. 19. Apiaceae. Lomatium suksdorfii. Suksdorfin. Suppresses HIV-1 viral replication. 20. Areschougiaceae. Agardhiella tenera (J. Agardh) F. Schmitz. Sulfonated polysaccharides.

  17. DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells

    NARCIS (Netherlands)

    Arrighi, Jean-François; Pion, Marjorie; Garcia, Eduardo; Escola, Jean-Michel; van Kooyk, Yvette; Geijtenbeek, Teunis B.; Piguet, Vincent

    2004-01-01

    Dendritic cells (DCs) are essential for the early events of human immunodeficiency virus (HIV) infection. Model systems of HIV sexual transmission have shown that DCs expressing the DC-specific C-type lectin DC-SIGN capture and internalize HIV at mucosal surfaces and efficiently transfer HIV to CD4+

  18. Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

    Directory of Open Access Journals (Sweden)

    Angela RI Meyrelles

    2016-02-01

    Full Text Available This study investigated the rate of human papillomavirus (HPV persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample, re-infection (detection of different types of HPV in the 2 samples, and type-specific HPV persistence (the same HPV type found in both samples. An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30% or re-infection (20%. A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79. Our findings show that bonafide (type-specific HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

  19. Frequent Occurrence of Pain and Prescription Opioid Use for Treatment of Pain Among Women with and at Risk for HIV Infection.

    Science.gov (United States)

    Sharma, Anjali; Hoover, Donald R; Shi, Qiuhu; Tsao, Jennie C I; Cox, Christopher; Gustafson, Deborah R; Weber, Kathleen; Greenblatt, Ruth M; Aouizerat, Bradley E; Plankey, Michael W

    2017-06-19

    Pain is frequent and underreported among HIV+ women. We determined occurrence and severity of pain, and types of pain treatments used among HIV+ and HIV- women. Cross-sectional analyses of pain as measured by the Brief Pain Inventory Short Form, and related pain therapies nested in the Women's Interagency HIV Study (WIHS). Multiple variable linear regression models examined differences by HIV status in pain severity and pain interference in general activity, mood, ability to walk, work, relationships with others, sleep, and enjoyment of life. Among 1393 HIV+ and 587 HIV- participants with median age 47-48 years, there was no statistically significant difference in pain reported within the past week by HIV status (HIV+ 50% vs. 49% HIV-, p = 0.70). Ratings of pain severity and interference were similar between HIV+ and HIV- women, as was receipt of pain medication (58% HIV+ vs. 56% HIV-). Pain medications most frequently used were: NSAIDS (90% HIV+, 96% HIV-), opioids (65% HIV+, 67% HIV-), topical anesthetics (46% HIV+, 56% HIV-), muscle relaxants (23% HIV+, 14% HIV-), and anticonvulsants (23% HIV+, 14% HIV-). Nearly half of predominantly low income, minority women reported pain in the past week, and two-thirds reported opioid use for pain management. The occurrence, severity, and treatment of pain did not differ by HIV status, nor did report of pain interference with mood or function. Additional research is needed to better characterize pain etiology among HIV+ women in the era of potent antiretroviral therapy, and determine the extent to which pain severity and type of medication used for pain treatment impact HIV disease outcomes.

  20. A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis.

    Science.gov (United States)

    Bjordal, Jan Magnus; Bensadoun, Rene-Jean; Tunèr, Jan; Frigo, Lucio; Gjerde, Kjersti; Lopes-Martins, Rodrigo Ab

    2011-08-01

    The purpose of this study is to review the effects of low-level laser therapy (LLLT) in the prevention and treatment of cancer therapy-induced oral mucositis (OM). A systematic review and meta-analysis of randomised placebo-controlled trials of LLLT performed during chemotherapy or radiation therapy in head and neck cancer patients. We found 11 randomised placebo-controlled trials with a total of 415 patients; methodological quality was acceptable at 4.10 (SD ± 0.74) on the 5-point Jadad scale. The relative risk (RR) for developing OM was significantly (p = 0.02) reduced after LLLT compared with placebo LLLT (RR = 2.03 (95% CI, 1.11 to 3.69)). This preventive effect of LLLT improved to RR = 2.72 (95% CI, 1.98 to 3.74) when only trials with adequate doses above 1 J were included. For treatment of OM ulcers, the number of days with OM grade 2 or worse was significantly reduced after LLLT to 4.38 (95% CI, 3.35 to 5.40) days less than placebo LLLT. Oral mucositis severity was also reduced after LLLT with a standardised mean difference of 1.33 (95% CI, 0.68 to 1.98) over placebo LLLT. All studies registered possible side-effects, but they were not significantly different from placebo LLLT. There is consistent evidence from small high-quality studies that red and infrared LLLT can partly prevent development of cancer therapy-induced OM. LLLT also significantly reduced pain, severity and duration of symptoms in patients with cancer therapy-induced OM.

  1. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

    Directory of Open Access Journals (Sweden)

    Maia Hightower

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

  2. HIV Structural Database

    Science.gov (United States)

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

  3. HIV Stigma in Prisons and Jails: Results from a Staff Survey.

    Science.gov (United States)

    Belenko, Steven; Dembo, Richard; Copenhaver, Michael; Hiller, Matthew; Swan, Holly; Albizu Garcia, Carmen; O'Connell, Daniel; Oser, Carrie; Pearson, Frank; Pankow, Jennifer

    2016-01-01

    With numerous HIV service gaps in prisons and jails, there has been little research on HIV stigma attitudes among correctional staff. Such attitudes may undermine HIV services for inmates at risk of or infected with HIV. This HIV stigma attitudes survey among 218 correctional staff in 32 US facilities (1) provides an overview of staff's stigma attitudes, (2) reports psychometric analyses of domains in Earnshaw and Chaudoir's HIV Stigma Framework (HSF), and (3) explores differences in stigma attitudes among different staff types. Overall, correctional and medical staff expressed non stigmatizing attitudes toward people living with HIV/AIDS, but perceived that stigma and discrimination exist in others. Factor analyses revealed a three factor structure capturing two mechanisms of the HSF (prejudice, discrimination). Few factor score differences were found by staff type or setting. Implications for correctional HIV services and future research on HIV stigma attitudes are discussed.

  4. Seroepidemiology of high-risk HPV in HIV-negative and HIV-infected MSM: the H2M study

    NARCIS (Netherlands)

    Mooij, Sofie H.; van der Klis, Fiona R. M.; van der Sande, Marianne A. B.; Schepp, Rutger M.; Speksnijder, Arjen G. C. L.; Bogaards, Johannes A.; de Melker, Hester E.; de Vries, Henry J. C.; Snijders, Peter J. F.; van der Loeff, Maarten F. Schim

    2013-01-01

    Men who have sex with men (MSM), in particular HIV-infected MSM, are at increased risk for diseases related to human papilloma virus (HPV). Our goal was to assess the effect of HIV status on the presence of type-specific antibodies against seven high-risk HPV types in HPV-unvaccinated MSM. Moreover,

  5. Cyclophilin B enhances HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    DeBoer, Jason; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln, NE (United States)

    2016-02-15

    Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

  6. Do Customers Flee From HIV? A Survey of HIV Stigma and Its Potential Economic Consequences on Small Businesses in Tshwane (Pretoria), South Africa.

    Science.gov (United States)

    Chao, Li-Wei; Szrek, Helena; Leite, Rui; Ramlagan, Shandir; Peltzer, Karl

    2017-01-01

    HIV stigma and discrimination affect care-seeking behavior and may also affect entrepreneurial activity. We interview 2382 individuals in Pretoria, South Africa, and show that respondents believe that businesses with known HIV+ workers may lose up to half of their customers, although the impact depends on the type of business. Survey respondents' fear of getting HIV from consuming everyday products sold by the business-despite a real infection risk of zero-was a major factor driving perceived decline in customers, especially among food businesses. Respondents' perceptions of the decline in overall life satisfaction when one gets sick from HIV and the respondent's dislike of people with HIV were also important predictors of potential customer exit. We suggest policy mechanisms that could improve the earnings potential of HIV+ workers: reducing public health scare tactics that exacerbate irrational fear of HIV infection risk and enriching public health education about HIV and ARVs to improve perceptions about people with HIV.

  7. Human immunodeficiency virus type 2: pathogenesis and antiretroviral therapy

    NARCIS (Netherlands)

    M.E. van der Ende (Marchina)

    2000-01-01

    textabstractHuman immunodeficiency virus type1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and simian immunodeficiency virus (SIV) have been identified as hither unknown primate members of the Lentivirinae subfamily of the family Retroviridae in 1983, 1986 and 1985 respectively, HIV-1

  8. The Spanish HIV BioBank: a model of cooperative HIV research

    Directory of Open Access Journals (Sweden)

    Prieto Cristina

    2009-03-01

    Full Text Available Abstract Background The collection of samples from HIV-infected patients is the beginning of the chain of translational research. To carry out quality research that could eventually end in a personalized treatment for HIV, it is essential to guarantee the availability, quality and traceability of samples, under a strict system of quality management. Methods The Spanish HIV BioBank was created with the objectives of processing, storing and providing distinct samples from HIV/AIDS patients, categorized according to strictly defined characteristics, free of charge to research projects. Strict compliance to ethical norms is always guaranteed. Results At the moment, the HIV BioBank possesses nearly 50,000 vials containing different prospective longitudinal study sample types. More than 1,700 of these samples are now used in 19 national and international research projects. Conclusion The HIV BioBank represents a novel approach to HIV research that might be of general interest not only for basic and clinical research teams working on HIV, but also for those groups trying to establish large networks focused on research on specific clinical problems. It also represents a model to stimulate cooperative research among large numbers of research groups working as a network on specific clinical problems. The main objective of this article is to show the structure and function of the HIV BioBank that allow it to very efficiently release samples to different research project not only in Spain but also in other countries.

  9. Prevalence and Associations of Psychological Distress, HIV Infection and HIV Care Service Utilization in East Zimbabwe.

    Science.gov (United States)

    Tlhajoane, Malebogo; Eaton, Jeffrey W; Takaruza, Albert; Rhead, Rebecca; Maswera, Rufurwokuda; Schur, Nadine; Sherr, Lorraine; Nyamukapa, Constance; Gregson, Simon

    2017-02-13

    The correlation between mental health and sexual risk behaviours for HIV infection remains largely unknown in low and middle income settings. The present study determined the prevalence of psychological distress (PD) in a sub-Saharan African population with a generalized HIV epidemic, and investigated associations with HIV acquisition risk and uptake of HIV services using data from a cross-sectional survey of 13,252 adults. PD was measured using the Shona Symptom Questionnaire. Logistic regression was used to measure associations between PD and hypothesized covariates. The prevalence of PD was 4.5% (95% CI 3.9-5.1%) among men, and 12.9% (95% CI 12.2-13.6%) among women. PD was associated with sexual risk behaviours for HIV infection and HIV-infected individuals were more likely to suffer from PD. Amongst those initiated on anti-retroviral therapy, individuals with PD were less likely to adhere to treatment (91 vs. 96%; age- and site-type-adjusted odds ratio = 0.38; 95% CI 0.15, 0.99). Integrated HIV and mental health services may enhance HIV care and treatment outcomes in high HIV-prevalence populations in sub-Saharan Africa.

  10. Dermatomyositis and HIV

    Directory of Open Access Journals (Sweden)

    Mamata Chand

    2016-12-01

    Full Text Available HIV has been linked to several autoimmune disorders since its emergence in the 1980s. By affecting different cells and pathways in the immune system, HIV induces the development of certain autoimmune diseases while prohibiting the emergence of others. Dermatomyositis has been rarely described in patients with HIV. We present a case of dermatomyositis in a patient with HIV and explore the pathogenesis of autoimmune disorders in HIV focusing on dermatomyositis.

  11. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    2011-06-09

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

  12. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    2012-11-26

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

  13. Side Effects of HIV Medicines: HIV and Hepatotoxicity

    Science.gov (United States)

    ... Find HIV Treatment Services HIV and Mental Health HIV and Nutrition and Food Safety Print This Fact Sheet Entire Series Related Content AIDSource | HIV Treatment: Side Effects Need Help? Call 1-800- ...

  14. HIV/AIDS, HPV and Anal Cancer

    Science.gov (United States)

    Wang, Chia-ching J.; Sparano, Joseph; Palefsky, Joel M.

    2016-01-01

    SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index. PMID:27889034

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... and the disease it causes (AIDS) are often linked and referred to as "HIV/AIDS." HIV can ... HIV Related? Drug misuse and addiction have been linked with HIV/AIDS since the beginning of the ...

  16. Global HIV/AIDS Epidemic

    Science.gov (United States)

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

  17. HIV / AIDS: An Unequal Burden

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 ... high-risk category, emphasizes Dr. Cargill. Photo: iStock HIV and Pregnancy Are there ways to help HIV- ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the ...

  19. HIV/AIDS in Women

    Science.gov (United States)

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

  20. 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 – ... and to help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human ...

  1. Serodiagnostic profiles of HIV and HIV pathogenesis in vivo

    NARCIS (Netherlands)

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

    1988-01-01

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

  2. Impairments of Motor Function While Multitasking in HIV.

    Science.gov (United States)

    Kronemer, Sharif I; Mandel, Jordan A; Sacktor, Ned C; Marvel, Cherie L

    2017-01-01

    Human immunodeficiency virus (HIV) became a treatable illness with the introduction of combination antiretroviral therapy (CART). As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND). The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing). Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

  3. Impairments of Motor Function While Multitasking in HIV

    Directory of Open Access Journals (Sweden)

    Cherie L. Marvel

    2017-04-01

    Full Text Available Human immunodeficiency virus (HIV became a treatable illness with the introduction of combination antiretroviral therapy (CART. As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND. The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing. Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

  4. Time-Dependent, HIV-Tat-Induced Perturbation of Human Neurons In Vitro: Towards a Model for the Molecular Pathology of HIV-Associated Neurocognitive Disorders

    OpenAIRE

    Gurwitz, Kim T.; Richard J. Burman; Murugan, Brandon D.; Shaun Garnett; Tariq Ganief; Soares, Nelson C.; Joseph V. Raimondo; Jonathan M Blackburn

    2017-01-01

    A significant proportion of human immunodeficiency virus type 1 (HIV)-positive individuals are affected by the cognitive, motor and behavioral dysfunction that characterizes HIV-associated neurocognitive disorders (HAND). While the molecular etiology of HAND remains largely uncharacterized, HIV transactivator of transcription (HIV-Tat) is thought to be an important etiological cause. Here we have used mass spectrometry (MS)-based discovery proteomics to identify the quantitative, cell-wide ch...

  5. Human Herpesvirus Type-8-associated Large B Cell Lymphoma (HHV-8-LBL). A Non- Serous Extra-Cavitary Variant of Primary Effusion Lymphoma in an HIV-Infected Man: A Case Report and Review of the Literature

    Science.gov (United States)

    Foster, William R.; Bischin, Alina; Dorer, Russell; Aboulafia, David M.

    2017-01-01

    BACKGROUND Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma subtype primarily seen in human immunodeficiency virus (HlV)-infected individuals with low CD4+ cell counts and elevated HIV viral loads. It is always associated with human herpesvirus type-8 (HHV-8) and in 80% of cases is also associated with Epstein Barr Virus (EBV). Less commonly, PEL presents in patients with advanced age and other conditions associated with altered immunity, including malignancy, liver cirrhosis, and immunosuppressive medications. It is a tumor of B-cell lineage; however, it shows a “null” phenotype, rarely expressing pan-B cell surface antigens. It does usually express CD45, CD30, CD38, CD138 and MUM1 and is characterized by lymphomatous effusions in body cavities but not lymphadenopathy. It is an aggressive lymphoma; average median survival time is less than a year. HHV-8-associated large B-cell Lymphoma (HHV-8-LBL) is a second variant of PEL that is both solid and extra-cavitary. It has immunoblastic and/or anaplastic morphological features, a distinct immuno-histochemical staining pattern, and may have a different clinical presentation than classic PEL. METHODS We describe the case of a 57-year-old HIV-infected man who presented with a slow growing and asymptomatic abdominal mass. An excisional biopsy showed malignant large cells with prominent cytoplasm that were positive for pan-B cell antigen CD20, HHV-8 and EBV, and negative for CD138, CD10, BCL-6, CD3 and CD30. Ki-67 labeling index was 90%. He was diagnosed with stage IIIA HHV-8-LBL, and he was treated with six cycles of R-EPOCH (rituximab, etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) infusion chemotherapy. He remains in complete remission (CR) 12 months post-treatment. We also performed a Medline and Embase search to better understand the clinical findings of this patient and the unique attributes of HHV-8-LBL. Focusing our search on English language articles, we identified 83

  6. Productive HIV-1 infection is enriched in CD4(-)CD8(-) double negative (DN) T cells at pleural sites of dual infection with HIV and Mycobacterium tuberculosis.

    Science.gov (United States)

    Meng, Qinglai; Canaday, David H; McDonald, David J; Mayanja-Kizza, Harriet; Baseke, Joy; Toossi, Zahra

    2016-01-01

    A higher human immunodeficiency virus 1 (HIV-1) viral load at pleural sites infected with Mycobacterium tuberculosis (MTB) than in peripheral blood has been documented. However, the cellular source of productive HIV infection in HIV-1/MTB-coinfected pleural fluid mononuclear cells (PFMCs) remains unclear. In this study, we observed significant quantities of HIV-1 p24(+) lymphocytes in PFMCs, but not in peripheral blood mononuclear cells (PBMCs). HIV-1 p24(+) lymphocytes were mostly enriched in DN T cells. Intracellular CD4 expression was detectable in HIV-1 p24(+) DN T cells. HIV-1 p24(+) DN T cells showed lower surface expression of human leukocyte antigen (HLA)-ABC and tetherin than did HIV-1 p24(+) CD4 T cells. Upon in vitro infection of PFMC CD4 T cells from TB mono-infected subjects, Nef- and/or Vpu-deleted HIV mutants showed lower generation of HIV-1 p24(+) DN T cells than the wild-type virus. These data indicate that productively HIV-1-infected DN T cells, generated through down-modulation of surface CD4, likely by HIV-1 Nef and Vpu, are the predominant source of HIV-1 at pleural sites of HIV/MTB coinfection.

  7. Molecular Typing of Treponema pallidum in Denmark

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Cowan, Susan; Gerstoft, Jan

    2016-01-01

    The aim of this nationwide study is to determine the strain type diversity among patients diagnosed with syphilis by PCR during a 4-year period in Denmark. Epidemiological data, including HIV status, for all patients were obtained from the Danish national syphilis registration system. Molecular......%) of the patients reported acquiring syphilis in Denmark. Among patients with concurrent HIV, 9 full strain types were identified and no difference in strain type was found by HIV status (p = 0.197). In conclusion, the majority of patients were infected in Denmark and the HIV-infected syphilis patients were...

  8. Pregnancy, contraceptive use, and HIV acquisition in HPTN 039: relevance for HIV prevention trials among African women.

    Science.gov (United States)

    Reid, Stewart E; Dai, James Y; Wang, Jing; Sichalwe, Bupe N; Akpomiemie, Godspower; Cowan, Frances M; Delany-Moretlwe, Sinead; Baeten, Jared M; Hughes, James P; Wald, Anna; Celum, Connie

    2010-04-01

    Biomedical HIV prevention trials enroll sexually active women at risk of HIV and often discontinue study product during pregnancy. We assessed risk factors for pregnancy and HIV acquisition, and the effect of pregnancy on time off study drug in HIV Prevention Trials Network 039. A total of 1358 HIV negative, herpes simplex virus type 2-seropositive women from South Africa, Zambia, and Zimbabwe were enrolled and followed for up to 18 months. A total of 228 pregnancies occurred; time off study drug due to pregnancy accounted for 4% of woman-years of follow-up among women. Being pregnant was not associated with increased HIV risk (hazard ratio 0.64, 95% confidence interval 0.23-1.80, P = 0.40). However, younger age was associated with increased risk for both pregnancy and HIV. There was no association between condom use as a sole contraceptive and reduced pregnancy incidence; hormonal contraception was not associated with increased HIV risk. Bacterial vaginosis at study entry was associated with increased HIV risk (hazard ratio 2.03, P = 0.02). Pregnancy resulted in only a small amount of woman-time off study drug. Young women are at high risk for HIV and are an appropriate population for HIV prevention trials but also have higher risk of pregnancy. Condom use was not associated with reduced incidence of pregnancy.

  9. Non-Communicable Disease Preventive Screening by HIV Care Model

    OpenAIRE

    Rhodes, Corinne M.; Chang, Yuchiao; Regan, Susan; Triant, Virginia A.

    2017-01-01

    Importance The Human Immunodeficiency Virus (HIV) epidemic has evolved, with an increasing non-communicable disease (NCD) burden emerging and need for long-term management, yet there are limited data to help delineate the optimal care model to screen for NCDs for this patient population. Objective: The primary aim was to compare rates of NCD preventive screening in persons living with HIV/AIDS (PLWHA) by type of HIV care model, focusing on metabolic/cardiovascular disease (CVD) and cancer scr...

  10. Species tropism of HIV-1 modulated by viral accessory proteins

    OpenAIRE

    Masako eNomaguchi; Naoya eDoi; Yui eMatsumoto; Yosuke eSakai; Sachi eFujiwara; Akio eAdachi

    2012-01-01

    Human immunodeficiency virus type 1 (HIV-1) is tropic and pathogenic only for humans, and does not replicate in macaque monkeys routinely used for experimental infections. This specially narrow host range (species tropism) has impeded much the progress of HIV-1/acquired immunodeficiency syndrome (AIDS) basic research. Extensive studies on the underlying mechanism have revealed that Vif, one of viral accessory proteins, is critical for the HIV-1 species tropism in addition to Gag-capsid protei...

  11. FDA-Approved HIV Medicines

    Science.gov (United States)

    ... Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets FDA-Approved HIV Medicines Search Search ... This Fact Sheet Entire Series Related Content AIDSource | Treatment: Medication FDA Approval of ... | HIV/AIDS Medicines Drugs That Fight HIV-1 HIV and ...

  12. Molecular analysis of critical sequences within the EBNA-2 type 1 gene from Epstein-Barr virus isolates from patients with infectious mononucleosis, tonsillar hyperplasia, and HIV infection

    NARCIS (Netherlands)

    Al-Homsi, A. S.; Berger, C.; van Baarle, D.; Kersten, M. J.; Klein, M. R.; McQuain, C.; van Oers, R.; Knecht, H.

    1998-01-01

    EBNA-2 is the first protein to be detected after infection of primary B lymphocytes by Epstein-Barr virus (EBV) and plays an essential role as transcriptional activator in EBV-induced lymphocyte transformation. We analysed by PCR and sequencing regions of the EBNA-2 type 1 gene from isolates from 13

  13. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

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

  14. Low-Energy Helium-Neon Laser Therapy Induces Repigmentation and Improves the Abnormalities of Cutaneous Microcirculation in Segmental-Type Vitiligo Lesions

    Directory of Open Access Journals (Sweden)

    Chieh-Shan Wu

    2008-04-01

    Full Text Available Segmental vitiligo (SV is a special form of vitiligo occurring in a dermatomal distribution, and an abnormality involving the sympathetic nerves supplying the affected dermatome is known to underlie this disorder. Previously, we have shown that SV is associated with an abnormal increase in cutaneous blood flow and adrenoceptor responses in the affected areas. Since SV is resistant to conventional forms of therapy, its management represents a challenge for dermatologists. Low energy helium-neon lasers (He-Ne laser, wavelength 632.8nm have been employed as a therapeutic instrument in many clinical situations, including vitiligo management and repair of nerve injury. The purpose of this study was to evaluate the effectiveness and safety of He-Ne lasers in treating SV, and determine their effects on the repair of sympathetic nerve dysfunction. Forty patients with stable-stage SV on the head and/or neck were enrolled in this study. He-Ne laser irradiation was administered locally at 3.0J/cm2 with point stimulation once or twice weekly. Cutaneous microcirculatory assessments in six SV patients were performed using a laser Doppler flowmeter. The sympathetic adrenoceptor response of cutaneous microcirculation was determined by measuring cutaneous blood flow before, during and after iontophoresis with sympathomimetic drugs (phenylephrine, clonidine and propranolol. All measurements of microcirculation obtained at SV lesions were simultaneously compared with contralateral normal skin, both before and after He-Ne laser treatment. After an average of 17 treatment sessions, initial repigmentation was noticed in the majority of patients. Marked repigmentation (> 50% was observed in 60% of patients with successive treatments. Cutaneous blood flow was significantly higher at SV lesions compared with contralateral skin, but this was normalized after He-Ne laser treatment. In addition, the abnormal decrease in cutaneous blood flow in response to clonidine was improved by He-Ne laser therapy. Our study showed that He-Ne laser therapy is an effective treatment for SV by normalizing dysfunctions of cutaneous blood flow and adrenoceptor responses in SV patients. Thus, the beneficial effects of He-Ne laser therapy may be mediated in part by a reparative effect on sympathetic nerve dysfunction.

  15. Understanding HIV-Related Stigma and Discrimination in a "Blameless" Population

    Science.gov (United States)

    Cao, Xiaobin; Sullivan, Sheena G.; Xu, Jie; Wu, Zunyou

    2006-01-01

    HIV-related stigma and discrimination are major barriers to the successful control of HIV. Stigma is associated with the disease as well as the behaviors that lead to infection. A qualitative study was conducted to identify the reasons, sources, and types of HIV-related stigma prevalent in rural China. Eighty in-depth interviews were conducted…

  16. Evasion from NK cell-mediated immune responses by HIV-1

    Science.gov (United States)

    Jost, Stephanie; Altfeld, Marcus

    2012-01-01

    Human immunodeficiency virus type 1 (HIV-1) mostly owes its success to its ability to evade host immune responses. Understanding viral immune escape mechanisms is prerequisite to improve future HIV-1 vaccine design. This review focuses on the strategies that HIV-1 has evolved to evade recognition by natural killer (NK) cells. PMID:22626930

  17. Towards virological monitoring of HIV-1 drug resistance in resource-limited settings

    NARCIS (Netherlands)

    Aitken, S.C.

    2014-01-01

    HIV-1 treatment monitoring is important to ensure effective viral suppression and prevent the development of HIV-1 drug resistance. Commercial assays for HIV-1 treatment monitoring are generally costly and complex, and require plasma as a sample type for testing. The components of this thesis are

  18. Identification of HIV-1 Tat-Associated Proteins Contributing to HIV-1 Transcription and Latency

    Science.gov (United States)

    Jean, Maxime Junior; Power, Derek; Kong, Weili; Huang, Huachao; Santoso, Netty; Zhu, Jian

    2017-01-01

    Human immunodeficiency virus type 1 (HIV-1) Tat is a virus-encoded trans-activator that plays a central role in viral transcription. We used our recently developed parallel analysis of in vitro translated open reading frames (ORFs) (PLATO) approach to identify host proteins that associate with HIV-1 Tat. From this proteomic assay, we identify 89 Tat-associated proteins (TAPs). We combine our results with other datasets of Tat or long terminal repeat (LTR)-associated proteins. For some of these proteins (NAT10, TINP1, XRCC5, SIN3A), we confirm their strong association with Tat. These TAPs also suppress Tat-mediated HIV-1 transcription. Removing suppression of HIV-1 transcription benefits the reversal of post-integrated, latent HIV-1 proviruses. We demonstrate that these transcriptionally suppressing TAPs contribute to HIV-1 latency in Jurkat latency (J-LAT) cells. Therefore, our proteomic analysis highlights the previously unappreciated TAPs that play a role in maintaining HIV-1 latency and can be further studied as potential pharmacological targets for the “shock and kill” HIV-1 cure strategy. PMID:28368303

  19. Mechanisms of HIV persistence in HIV reservoirs.

    Science.gov (United States)

    Mzingwane, Mayibongwe L; Tiemessen, Caroline T

    2017-03-01

    The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half-life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia. Some anatomical reservoirs that may harbor such cells include the brain and the central nervous system, the gastrointestinal tract and the gut-associated lymphoid tissue and other lymphoid organs, and the genital tract. The presence of immune cells and other HIV susceptible cells, occurring in differing compositions in anatomical reservoirs, coupled with variable and poor drug penetration that results in suboptimal drug concentrations in some sites, are all likely factors that fuel the continued low-level replication and persistent viremia during treatment. Latently, HIV-infected CD4+ T cells harboring replication-competent virus, HIV cell-to-cell spread, and HIV-infected T cell homeostatic proliferation due to chronic immune activation represent further drivers of this persistent HIV viremia during highly active antiretroviral therapy. Copyright © 2017 John Wiley & Sons, Ltd.

  20. HIV-1 is not a major driver of increased plasma IL-6 levels in chronic HIV-1 disease

    Science.gov (United States)

    Shive, Carey L.; Biancotto, Angélique; Funderburg, Nicholas T.; Pilch-Cooper, Heather A.; Valdez, Hernan; Margolis, Leonid; Sieg, Scott F.; McComsey, Grace A.; Rodriguez, Benigno; Lederman, Michael M.

    2012-01-01

    Objective Increased plasma IL-6 levels have been associated with HIV-1 disease progression risk, yet the drivers of IL-6 production in HIV-1 infection are not known. This study was designed to explore the relationship between HIV-1 replication and IL-6 induction. Design Correlations between plasma levels of IL-6 and HIV-1 RNA were examined in two clinical studies. To more directly assess the induction of IL-6 by HIV-1, several cell and tissue types that support HIV-1 replication in vivo were infected with HIV-1 and expression of IL-6 was measured. Methods Spearman’s rank correlations were used to examine the relationship between plasma levels of IL-6 and HIV-1 RNA. Macrophages, and colonic and lymph node histocultures were infected with HIV-1 or stimulated with bacterial products, LPS or flagellin, and IL-6 levels in supernatant were measured by ELISA or multiplex bead assay. Results In the clinical studies there was weak or no correlation between plasma levels of IL-6 and HIV-1 RNA but IL-6 levels were correlated with plasma levels of the LPS coreceptor CD14. Macrophages stimulated with LPS or flagellin showed robust production of IL-6, but there was no increase in IL-6 production after HIV-1 infection. IL-6 expression was not increased in lymph node histocultures obtained from HIV-1 infected subjects nor after productive HIV-1 infection of colonic or lymph node histocultures ex vivo. Conclusions We find no evidence that HIV-1 replication is an important driver of IL-6 expression in vivo or in in vitro systems. PMID:22659649

  1. Development of a one-tube multiplex reverse transcriptase-polymerase chain reaction assay for the simultaneous amplification of HIV type 1 group M gag and env heteroduplex mobility assay fragments

    OpenAIRE

    Cham, F.; Heyndrickx, L; Janssens, W; Vereecken, K.; Houwer, K.; Coppens, S.; Van Der Auwera, G.; Whittle, H; van der Groen, G

    2000-01-01

    The emergence of intersubtype recombinant HIV-1 isolates has made it imperative to analyze different regions of HIV-1 genomes. For this purpose a one-tube multiplex RT-PCR, coamplifying first-round amplicons that allow amplification of gag and env heteroduplex mobility assay (HMA) fragments from different HIV-1 group M isolates, was developed, starting with plasma samples. The multiplex RT-PCR assay is sensitive: 115 of 136 (84.5%) samples were positive for both gag and env, positive amplific...

  2. Promoter interference mediated by the U3 region in early-generation HIV-1-derived lentivirus vectors can influence detection of transgene expression in a cell-type and species-specific manner.

    Science.gov (United States)

    Ginn, Samantha L; Fleming, Jane; Rowe, Peter B; Alexander, Ian E

    2003-08-10

    In a previous study using an early-generation VSV-G-pseudotyped lentivirus vector encoding enhanced green fluorescent protein (EGFP) under the transcriptional control of a human cytomegalovirus (CMV) immediate-early promoter, we examined transduction efficiency in dissociated dorsal root ganglia (DRG) cultures. In cultures of murine origin, transgene expression was observed solely in the sensory neurons with the stromal cell population failing to show evidence of transduction. In contrast, efficient and sustained transduction of both sensory neurons and the stromal cell population was observed in cultures of human origin. Given the widespread use of murine models in preclinical gene therapy studies, in the current study we investigated the basis of this apparent neuron specificity of lentivirus-mediated transduction in murine DRG cultures. The interspecies differences persisted at high multiplicities of infection, and irrespective of whether lentiviral vector stocks were packaged in the presence or absence of human immunodeficiency virus type 1 (HIV-1) accessory proteins. Cell-type specificity of CMV promoter expression, tropism of the VSV-G envelope, and blocks to molecular transduction were also precluded as possible mechanisms, thereby implicating transcriptional repression of the internal heterologous promoter. This promoter interference effect was found to be mediated by cis-acting sequences upstream of the core promoter elements located in the U3 region of the proviral long terminal repeats (LTRs). Deletion of this region, as in late-generation self-inactivating (SIN) lentivirus vectors, relieves this effect. This provides a basis for reevaluating data produced using early-generation U3-bearing lentivirus vectors and for reconciling these with results obtained using more contemporary SIN lentivirus vectors carrying a U3 deletion.

  3. HIV: Treatment and Comorbidity

    NARCIS (Netherlands)

    C. Rokx (Casper)

    2016-01-01

    markdownabstractClinicians worldwide strive to improve HIV care for their patients. Antiretroviral therapy prevents HIV related mortality and is lifelong. A clinical evaluation of these treatment strategies is necessary to identify strategies that may jeopardize treatment effectiveness and patient

  4. HIV and Hepatitis B

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Hepatitis B Last Reviewed: July 24, 2017 ...

  5. HIV and Tuberculosis (TB)

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Tuberculosis (TB) Last Reviewed: July 26, 2017 ...

  6. HIV/AIDS Basics

    Science.gov (United States)

    ... Partner Spotlight Awareness Days Get Tested Find an HIV testing site near you. Enter ZIP code or ... AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets ...

  7. Travelers' Health: HIV Infection

    Science.gov (United States)

    ... Share Compartir Chapter 3 - Histoplasmosis Chapter 3 - Influenza HIV Infection Philip J. Peters, John T. Brooks INFECTIOUS AGENT ... skin (see Chapter 8, Health Care Workers ). EPIDEMIOLOGY HIV infection occurs worldwide. As of the end of 2014, ...

  8. HIV Resistance Testing

    Science.gov (United States)

    ... 2016 Select a Language: Fact Sheet 126 HIV Resistance Testing WHAT IS RESISTANCE? HOW DOES RESISTANCE DEVELOP? ... one or more ARVs. This is called transmitted resistance. The more that HIV multiplies, the more mutations ...

  9. Mouth Problems and HIV

    Science.gov (United States)

    ... AIDS > Mouth Problems and HIV Mouth Problems and HIV Main Content This information is for people who ... fever blisters. Sometimes Yes Prescription pill can reduce healing time and frequency of outbreaks. Click to enlarge ...

  10. Exosomes: Implications in HIV-1 Pathogenesis

    Science.gov (United States)

    Madison, Marisa N.; Okeoma, Chioma M.

    2015-01-01

    Exosomes are membranous nanovesicles of endocytic origin that carry host and pathogen derived genomic, proteomic, and lipid cargos. Exosomes are secreted by most cell types into the extracellular milieu and are subsequently internalized by recipient cells. Upon internalization, exosomes condition recipient cells by donating their cargos and/or activating various signal transduction pathways, consequently regulating physiological and pathophysiological processes. The role of exosomes in viral pathogenesis, especially human immunodeficiency virus type 1 [HIV-1] is beginning to unravel. Recent research reports suggest that exosomes from various sources play important but different roles in the pathogenesis of HIV-1. From these reports, it appears that the source of exosomes is the defining factor for the exosomal effect on HIV-1. In this review, we will describe how HIV-1 infection is modulated by exosomes and in turn how exosomes are targeted by HIV-1 factors. Finally, we will discuss potentially emerging therapeutic options based on exosomal cargos that may have promise in preventing HIV-1 transmission. PMID:26205405

  11. Kaleidoscope of autoimmune diseases in HIV infection.

    Science.gov (United States)

    Roszkiewicz, Justyna; Smolewska, Elzbieta

    2016-11-01

    Within the last 30 years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.

  12. Assessment of the ability of a fourth-generation immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen to detect both acute and recent HIV infections in a high-risk setting.

    Science.gov (United States)

    Pandori, Mark W; Hackett, John; Louie, Brian; Vallari, Ana; Dowling, Teri; Liska, Sally; Klausner, Jeffrey D

    2009-08-01

    An immunoassay (IA) that simultaneously detects both antibody to human immunodeficiency virus (HIV) and HIV p24 antigen (Architect HIV Ag/Ab Combo) was evaluated for its ability to detect HIV infection by using a panel of specimens collected from individuals recently infected with HIV type 1 (HIV-1). This IA was found to be capable of detecting the majority (89%) of infections, including 80% of those considered acute infections based on the presence of HIV RNA and the lack of detectable antibody to HIV. Substantial improvements in detection of recent infections by the Architect HIV Ag/Ab Combo relative to previous generations of IAs as well as the capacity to detect acute infections have important implications for HIV prevention strategies.

  13. Curr Opin HIV AIDS

    OpenAIRE

    Zewdie, D.; Cahn, P.; McClure, C; Bataringaya, J.

    2008-01-01

    PURPOSE OF REVIEW: There is growing recognition that greater investment in research is needed to expand our knowledge and understanding of how to scale up HIV programmes effectively and equitably in the context of weak health systems. Current debates acknowledge that there remains a gap in evidence on how HIV resources can best be managed to contribute to building health system capacity; how to integrate HIV interventions into primary healthcare systems; and how HIV scale-up is affecting othe...

  14. Immuno-andrology/IVF/AID/HIV.

    Science.gov (United States)

    Hafez, E S; Zea, H B; Arias, E

    1987-01-01

    Several research projects are suggested related to artificial insemination by donor (AID), rectal insemination, autoimmunity in the male reproductive system and isoimmunity in the female tract and HIV transmission. The mixed antiglobulin reaction test is suggested as an early indicator of whether semen for donor insemination is free of HIV. Such semen should also be screened for hepatitis B. The immune responses to rectal insemination should be explored, as evidence from laboratory animals and homosexual men suggests that this practice may compromise the immune system. The possibility that the high titer of HIV in semen could adversely affect women using IUDs, via the exposed tail of the device, should be investigated. A protocol for insuring that semen for artificial insemination is free of HIV is presented. 21 other research experiments are suggested by title only, including 13 types of testing for studies of the immune response in malignancy.

  15. Update on human immunodeficiency virus (HIV)-2 infection.

    Science.gov (United States)

    Campbell-Yesufu, Omobolaji T; Gandhi, Rajesh T

    2011-03-15

    Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges.

  16. Assessment of the protective effect of male circumcision from HIV ...

    African Journals Online (AJOL)

    The study concludes that male circumcision provides a strong protection against acquisition of HIV infection. Hence, it can be considered as a possible way of reducing the spread of HIV infection in areas where the practice is rare. A comprehensive study to assess the association between circumcision and different types ...

  17. HIV-1, how llamas help us fight the AIDS pandemic

    NARCIS (Netherlands)

    Strokappe, N.M.|info:eu-repo/dai/nl/314411534

    2013-01-01

    Human Immunodeficiency Virus type 1 (HIV-1) is one of the major health problems worldwide and has been for over thirty years. Most (67%) of the people infected with HIV-1 are living in sub-Saharan Africa. Here, the access to treatments is limited and most women are not in a position to protect

  18. A comparative analysis of perceived stigma among HIV-positive ...

    African Journals Online (AJOL)

    The purpose of this paper was to address two questions: (i) Do Ghanaian and African American males with HIV/AIDS experience different types and degrees of stigma? and (ii) Is the impact of stigma associated with HIV/AIDS on the self different for Ghanaian and African American males? A quantitative method was used, ...

  19. Hearing disorder in HIV positive adult patients not on Anti ...

    African Journals Online (AJOL)

    Objectives: To determine the prevalence and type of hearing disorders in HIV positive patients not on anti - retroviral drugs (ARVs) and correlate this with the world health Organization (WHO) stage of HIV disease and CD4 positive cell counts. Design: Case control study. Setting: comprehensive care clinic (CCC) and ...

  20. immune response can measuring immunity to hiv during ...

    African Journals Online (AJOL)

    2005-11-01

    Nov 1, 2005 ... level, probably because of the difficulty of taking biopsies. In adults, one of the first events after HIV ... T-cell receptor (TCR) type have been identified in infants37 and adults.38 This results in a limited pattern of ..... Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in ...

  1. HIV/AIDS Education: What Works for Swaziland University Students?

    Science.gov (United States)

    Sukati, C. W. S.; Vilakati, Nokuthula; Esampally, Chandraiah

    2010-01-01

    Background: HIV/AIDS poses a major threat to development and poverty alleviation, particularly in Sub-Saharan Africa. Education has been declared an effective preventative approach and the single most powerful weapon against HIV transmission. However, there is a paucity of research on the type of education required, the appropriate…

  2. HIV associated lupus like nephropathy | Hamid | Ethiopian Journal ...

    African Journals Online (AJOL)

    BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)– seropositive patients are at a high risk for the development of a variety of acute and chronic renal diseases. Most patients with HIVAN are of African descent, presenting late in the course of their HIV-1 infection. The only reliable test to establish or rule out the ...

  3. Rheumatologic manifestations of HIV-1 and HTLV-1 infections.

    Science.gov (United States)

    Vassilopoulos, D; Calabrese, L H

    1998-09-01

    HIV infection is the new "great mimic." Although its more common signs and symptoms are well known, HIV infection sometimes presents with rheumatologic manifestations, as does human T-cell lymphotrophic virus type I (HTLV-I), the causative agent of adult T-cell leukemia. This review briefly describes these manifestations and presents a logical clinical approach to their diagnosis and treatment.

  4. Heart disease among children with HIV/AIDS attending the ...

    African Journals Online (AJOL)

    Background: There are very few published studies of heart disease in HIV infected children living in sub-Saharan Africa, a region with more than 50% of the world's population of HIV infected patients. Objectives: To determine the prevalence, and describe the type and clinical presentation of heart disease among children ...

  5. Raltegravir with optimized background therapy for resistant HIV-1 infection

    DEFF Research Database (Denmark)

    Steigbigel, Roy T; Cooper, David A; Kumar, Princy N

    2008-01-01

    BACKGROUND: Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs. METHODS: We conducted two identical trials in different geographic regions to evaluate the safety and efficacy...

  6. Molecular Mechanisms in Activation of Latent HIV-1

    NARCIS (Netherlands)

    H. Rafati (Haleh)

    2014-01-01

    markdownabstract__Abstract__ Finding a cure for the human immunodeficiency virus type 1 (HIV-1) is extremely challenging. Development of highly active anti-retroviral therapy (HAART), transformed HIV-1 infection from an acute syndrome into chronic disease. Although using HAART results in

  7. Breaking Barriers to an AIDS Model with Macaque-Tropic HIV-1 Derivatives

    OpenAIRE

    Kimata, Jason T; Hongmei Ruan; Rajesh Thippeshappa

    2012-01-01

    The development of an animal model of human immunodeficiency virus type 1 (HIV-1)/AIDS that is suitable for preclinical testing of antiretroviral therapy, vaccines, curative strategies, and studies of pathogenesis has been hampered by the human-specific tropism of HIV-1. Although simian immunodeficiency virus (SIV) or HIV-1/SIV chimeric viruses (SHIVs)-rhesus macaque models are excellent surrogates for AIDS research, the genetic differences between SIV or SHIV and HIV-1 limit their utility as...

  8. Relationship of race-, sexual orientation-, and HIV-related discrimination with adherence to HIV treatment: a pilot study.

    Science.gov (United States)

    Boarts, Jessica M; Bogart, Laura M; Tabak, Melanie A; Armelie, Aaron P; Delahanty, Douglas L

    2008-10-01

    Adherence to highly active antiretroviral therapy (HAART) must be close to perfect in order to maintain suppression of HIV viral load, and to prevent the development of drug resistant strains of HIV. People living with HIV (PLWH) often report low levels of adherence. One variable that has been linked to poor adherence is perceived discrimination; however, research has generally not considered the possible unique effects of different types of discrimination on adherence. The present pilot study aimed to examine the association of three types of discrimination (due to HIV+ status, race, or sexual orientation) with adherence among 57 PLWH. Logistic regression analyses were conducted to demonstrate the relationships between each type of discrimination and self-reported adherence. Racial discrimination significantly predicted lower adherence levels, whereas sexual orientation- and HIV-related discrimination did not. Results underscore the importance of addressing discrimination issues, specifically racial, when designing interventions to improve adherence to HAART.

  9. Type 1 and type 2 cytokine profiles in children exposed to or infected with vertically transmitted human immunodeficiency virus.

    OpenAIRE

    Lee, B. N.; Lu, J. G.; Kline, M.W.; Paul, M.; Doyle, M; Kozinetz, C; Shearer, W T; Reuben, J. M.

    1996-01-01

    In human immunodeficiency virus (HIV)-infected adults, cytokine production profiles switch from predominantly type 1 (interleukin-2 [IL-2] and gamma interferon [IFN-gamma]) to type 2 (IL-4 and IL-10) cytokines with disease progression. To test this hypothesis in vertically HIV-infected children, we measured cytokine transcription and production in rapid progressors (RPs), seroreverters (SRs), and those children exposed to HIV in utero (P0s). Production of type 1 and type 2 cytokines was measu...

  10. HIV protease inhibitor resistance

    NARCIS (Netherlands)

    Wensing, Annemarie M.J.; Fun, Axel; Nijhuis, Monique

    2017-01-01

    HIV protease is pivotal in the viral replication cycle and directs the formation of mature infectious virus particles. The development of highly specific HIV protease inhibitors (PIs), based on thorough understanding of the structure of HIV protease and its substrate, serves as a prime example of

  11. Primaer HIV-infektion

    DEFF Research Database (Denmark)

    Pedersen, C; Pedersen, B K

    1996-01-01

    , oesophageal candidiasis, meningoencephalitis, rhabdomyolysis and epiglottitis have been reported. The diagnosis of the acute HIV infection syndrome can be established by demonstrating antibodies to HIV or by demonstration of HIV antigen positivity. Detection of virus through culture or PCR may prove...

  12. Thrombocytopenia in HIV

    African Journals Online (AJOL)

    2007-06-15

    Jun 15, 2007 ... necessary tests are done initially and the correct treatment started. ... thrombocytopenia is prone to a more rapid acceleration of disease. ... Platelet life span is decreased in HIV-induced idiopathic thrompocytopenic purpura (ITP) and in. HIV patients without ITP. It seems as if HIV stimulates CD5+ cells.

  13. Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series: e0138115

    National Research Council Canada - National Science Library

    Renata Báez-Saldaña; Adriana Villafuerte-García; Pablo Cruz-Hervert; Guadalupe Delgado-Sánchez; Leticia Ferreyra-Reyes; Elizabeth Ferreira-Guerrero; Norma Mongua-Rodríguez; Rogelio Montero-Campos; Ada Melchor-Romero; Lourdes García-García

    2015-01-01

    ...) programs and epidemiology of infectious diseases. Objective To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS...

  14. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay.

    Science.gov (United States)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas T; Cramer, Frederik; Roth, Jack A; Poulsen, Hans S

    2010-04-15

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1). Therapeutic effect was evaluated in vitro in SCLC cell lines and in vivo in SCLC xenografted nude mice using the nonviral nanoparticle DOTAP/cholesterol for transgene delivery. INSM1-YCD/5-FC and INSM1-YCD-YUPRT/5-FC therapy induced high cytotoxicity in a range of SCLC cell lines. The highest therapeutic effect was obtained from the YCD-YUPRT fusion gene strategy. No cytotoxicity was induced after treatment of cell lines of other origin than SCLC. In addition the INSM1-YCD-YUPRT/5-FC therapy was superior to an established suicide gene system consisting of the herpes simplex virus thymidine kinase (HSVTK) gene and the prodrug ganciclovir. The superior effect was in part due to massive bystander cytotoxicity of YCD-YUPRT-produced toxins. Finally, INSM1-YCD-YUPRT/5-FC therapy induced significant tumor growth delay in SCLC xenografts compared with control-treated xenografts. The current study is the first to test cytosine deaminase-based suicide gene therapy for SCLC and the first to show an antitumor effect from the delivery of suicide gene therapeutics for SCLC in vivo.

  15. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer specific cytotoxicity and tumor growth delay

    Science.gov (United States)

    Christensen, Camilla L.; Gjetting, Torben; Poulsen, Thomas T.; Cramer, Frederik; Roth, Jack A.; Poulsen, Hans S.

    2012-01-01

    Purpose Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment and novel therapies are therefore in high demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug Experimental design The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter Insulinoma-associated 1 (INSM1). Therapeutic effect was evaluated in vitro in SCLC cell lines and in vivo in SCLC xenografted nude mice using the non-viral nanoparticle, DOTAP:Cholesterol for transgene delivery. Results INSM1-YCD/5-FC and INSM1-YCD-YUPRT/5-FC therapy induced high cytotoxicity in a range of SCLC cell lines. The highest therapeutic effect was obtained from the YCD-YUPRT fusion gene strategy. No cytotoxicity was induced after treatment of cell lines of other origin than SCLC. In addition the INSM1-YCD-YUPRT/5-FC therapy was superior to an established suicide gene system consisting of the Herpes Simplex Virus Thymidine Kinase (HSVTK) gene and prodrug Ganciclovir (GCV). The superior effect was in part due to massive bystander cytotoxicity of YCD-YUPRT-produced toxins. Finally, INSM1-YCD-YUPRT/5-FC therapy induced significant tumor growth delay in SCLC xenografts compared to control treated xenografts. Conclusions The current study is the first to test cytosine deaminase-based suicide gene therapy for SCLC and the first to demonstrate an anti-tumor effect from the delivery of suicide gene therapeutics for SCLC in vivo. PMID:20371678

  16. Increased Prevalence of Albuminuria in HIV-Infected Adults with Diabetes

    OpenAIRE

    Kim, Peter S.; Woods, Christian; Dutcher, Lauren; Georgoff, Patrick; Rosenberg, Alice; Mican, Jo Ann M.; Kopp, Jeffrey B.; Smith, Margo A.; Hadigan, Colleen

    2011-01-01

    Objective HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes. Research Design and Methods We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine >1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio >30 mg/g. Results The pre...

  17. 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.

  18. HIV antibodies for treatment of HIV infection

    Science.gov (United States)

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

    2016-01-01

    Summary The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Further, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure. PMID:28133794

  19. Human immunodeficiency virus type-2-A milder, kinder virus: An update

    Directory of Open Access Journals (Sweden)

    R Kannangai

    2012-01-01

    Full Text Available Human immunodeficiency virus type-2 (HIV-2 belongs to the family retroviridae which is phylogenetically clusters with SIV SM from sooty mangabeys. This virus is morphologically similar to human immunodeficiency virus type-1 (HIV-1 but has got only a 40% homology at the nucleotide level. There is a distinct geographical distribution of HIV-2 unlike HIV-1. There are currently eight subtypes/groups identified with subtype/group A responsible for the majority of infections. HIV-2 shows a considerable difference in the course of the disease. Clinical, haematological and immunological evaluation of individuals infected with HIV-2 has shown the virus to be less pathogenic than HIV-1 although the exact mechanism underlying this difference is not well defined. Similar to HIV-1, the HIV-2 isolates also showed distinct replicative and cytopathic characteristics. The transmission rate for HIV-2 compared to HIV-1 is very low both by heterosexual route and mother to child transmission. The clinical signs and symptoms of immunodeficiency associated with HIV-2 are similar to the ones seen among the HIV-1-infected individuals and they can also progress to AIDS. It is naturally resistant to NNRTI and hence the diagnosis become important as it affects the treatment strategy. Similar to HIV-1, HIV-2 strains of infected individuals also show mutations that can cause drug resistance. The current evidence suggests that there is no protective effective for HIV-2 against HIV-1.

  20. Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions.

    Science.gov (United States)

    McNicholl, Janet M

    2016-12-01

    Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.

  1. Worldwide molecular epidemiology of HIV Epidemiologia molecular do HIV no mundo

    Directory of Open Access Journals (Sweden)

    Henry I Z Requejo

    2006-04-01

    Full Text Available Human immunodeficiency virus (HIV is the worldwide disseminated causative agent of acquired immunodeficiency syndrome (AIDS. HIV is a member of the Lentivirus genus of Retroviridae family and is grouped in two types named HIV-1 and HIV-2. These viruses have a notable ability to mutate and adapt to the new conditions of human environment. A large incidence of errors at the transcriptional level results in changes on the genetic bases during the reproductive cycle. The elevated genomic variability of HIV has carried important implications for the diagnosis, treatment and prevention as well as epidemiologic investigations. The present review describes important definitions and geographical distribution of subtypes, circulating recombinant forms and other genomic variations of HIV. The present study aimed at leading students of Biomedical Sciences and public health laboratory staff guidance to general and specific knowledge about the genomic variability of the HIV.O vírus da imunodeficiência humana (HIV, disseminado em todo o mundo, é o agente responsável pela síndrome da imunodeficiência adquirida (Aids. O HIV é um membro do gênero Lentivirus da família Retroviridae e compreende os tipos HIV-1 e HIV-2. Esses vírus possuem notável capacidade de mutar e se adaptar às novas condições do ambiente humano. Uma grande incidência de erros ao nível transcricional do genoma resulta em alterações nas bases genéticas durante o ciclo reprodutivo. A elevada variabilidade genômica do HIV apresenta importantes implicações para o diagnóstico, tratamento e prevenção, bem como nas investigações epidemiológicas. A elaboração desta revisão traz importantes conceitos sobre definições e distribuição geográfica de subtipos, formas recombinantes circulantes e outras variações genômicas do HIV. O estudo pretendeu direcionar os estudantes de ciências biomédicas e os profissionais de laboratórios de saúde pública aos conhecimentos

  2. HIV vaccine strategies.

    Science.gov (United States)

    Nabel, Gary J

    2002-05-06

    Traditional methods of vaccine development have not produced effective vaccines for several prevalent infectious diseases, including AIDS, malaria and tuberculosis. These difficult diseases call attention to the importance of new approaches that profit from modern technologies. Successful efforts in the past have typically taken advantage of naturally occurring, protective immune responses, but this avenue is not readily available in certain cases, such as in HIV infection, where the immune system rarely confers protective immunity. However, there are alternative strategies and areas of research that may facilitate the development of highly effective vaccines. These include the identification of immunogens that elicit broadly neutralizing antibodies, determination of the molecular and cellular basis for immune responses to the components of the infectious agent, the identification of relevant forms of viral proteins for antigen presentation, stimulation of relevant T-cell types, and enhancement of antigen-presenting, dendritic cell function. Answering these basic research questions will aid in rational vaccine design. It is also extremely important to optimize techniques for the testing and production of new vaccines including the quantitation of immune responses in animals and in humans, identification of surrogate markers of immune protection, streamlined vaccine production, and rapid evaluation of candidate vaccines for testing in clinical trials. We have put these ideas into practice in two recent studies in which we generated enhanced cytotoxic T lymphocyte (CTL) responses, while retaining robust humoral responses, to wild-type viral proteins by immunizing mice with genetically modified forms of HIV-1 Env, Gag and Pol delivered in the form of plasmid DNA expression vectors.

  3. Identification of Host Micro RNAs That Differentiate HIV-1 and HIV-2 Infection Using Genome Expression Profiling Techniques

    Directory of Open Access Journals (Sweden)

    Krishnakumar Devadas

    2016-05-01

    Full Text Available While human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2 share many similar traits, major differences in pathogenesis and clinical outcomes exist between the two viruses. The differential expression of host factors like microRNAs (miRNAs in response to HIV-1 and HIV-2 infections are thought to influence the clinical outcomes presented by the two viruses. MicroRNAs are small non-coding RNA molecules which function in transcriptional and post-transcriptional regulation of gene expression. MiRNAs play a critical role in many key biological processes and could serve as putative biomarker(s for infection. Identification of miRNAs that modulate viral life cycle, disease progression, and cellular responses to infection with HIV-1 and HIV-2 could reveal important insights into viral pathogenesis and provide new tools that could serve as prognostic markers and targets for therapeutic intervention. The aim of this study was to elucidate the differential expression profiles of host miRNAs in cells infected with HIV-1 and HIV-2 in order to identify potential differences in virus-host interactions between HIV-1 and HIV-2. Differential expression of host miRNA expression profiles was analyzed using the miRNA profiling polymerase chain reaction (PCR arrays. Differentially expressed miRNAs were identified and their putative functional targets identified. The results indicate that hsa-miR 541-3p, hsa-miR 518f-3p, and hsa-miR 195-3p were consistently up-regulated only in HIV-1 infected cells. The expression of hsa-miR 1225-5p, hsa-miR 18a* and hsa-miR 335 were down modulated in HIV-1 and HIV-2 infected cells. Putative functional targets of these miRNAs include genes involved in signal transduction, metabolism, development and cell death.

  4. Attitudes and beliefs related to HIV/AIDS in urban religious congregations: barriers and opportunities for HIV-related interventions.

    Science.gov (United States)

    Bluthenthal, Ricky N; Palar, Kartika; Mendel, Peter; Kanouse, David E; Corbin, Dennis E; Derose, Kathryn Pitkin

    2012-05-01

    HIV-related stigmas have been seen as a barrier to greater religious congregation involvement in HIV prevention and care in the United States and elsewhere. We explored congregational and community norms and attitudes regarding HIV, sexuality, and drug use through a qualitative case study of 14 diverse religious congregations in Los Angeles County, California between December 2006 and May 2008. Data collected included semi-structured interviews with 57 clergy and lay leaders across the congregations, structured observations of congregational activities, review of archival documents, and a questionnaire on congregational characteristics. Across and within congregations, we found a wide range of views towards HIV, people with HIV, and populations at risk for HIV, from highly judgmental and exclusionary, to "loving the sinner, not the sin," to accepting and affirming. Attitudes and norms about HIV, homosexuality, and substance abuse appeared to be related to the type and intensity of congregational HIV-related activities. However, even among the higher activity congregations, we found a range of perceptions, including ones that were stigmatizing. Results suggest that affirming norms and attitudes are not a prerequisite for a congregation to initiate HIV activities, a finding relevant for HIV service providers and researchers seeking to engage congregations on this issue. HIV stigma reduction is not a prerequisite for congregational HIV involvement: both may occur simultaneously, or one before the other, and they dynamically affect each other. Strategies that are congruent with congregations' current levels of comfort and openness around HIV can themselves facilitate a process of attitudinal and normative change. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Diet and Nutrition and HIV

    Science.gov (United States)

    ... with HIV/AIDS: Diet and Nutrition--Entire Lesson HIV/AIDS Menu Menu HIV/AIDS HIV/AIDS Home ... code here Enter ZIP code here Living with HIV/AIDS: Diet and Nutrition--Entire Lesson for Veterans ...

  6. Basic HIV/AIDS Statistics

    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 | ... Center . Expand All Collapse All How many new HIV infections are there each year in the United ...

  7. Serological markers in HIV infection

    NARCIS (Netherlands)

    Lange, J. M.; Goudsmit, J.; de Wolf, F.; Coutinho, R. A.; van der Noordaa, J.

    1988-01-01

    HIV antigenaemia can be detected at or possibly before the onset of clinical symptoms of primary HIV infection. Approximately one week after the onset of HIV antigenaemia, a primary anti-HIV IgM response may occur. A week later, generally within 3 to 6 weeks after infection, anti-HIV IgG can be

  8. Markers for type II collagen breakdown predict the effect of disease-modifying treatment on long-term radiographic progression in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Landewé, Robert; Geusens, Piet; Boers, Maarten; van der Heijde, Désirée; Lems, Willem; te Koppele, Johan; van der Linden, Sjef; Garnero, Patrick

    2004-01-01

    To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression

  9. Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C M; Nielsen, C

    1989-01-01

    agglutinin, Pisum sativum agglutinin and phytohaem(erythro)agglutinin bound to gp120 of all three isolates. The carbohydrate of gp120 recognized by lectins was thus arranged in at least four types of glycans: a high mannose type glycan, a bisected hybrid or complex type glycan, a biantennary fucosylated...... complex type glycan and a triantennary bisected complex type glycan. Only lectins which bound at least one of the four types of glycans were capable of inhibiting fusion of HIV-infected cells with CD4 cells by a carbohydrate-specific interaction with the HIV-infected cells. Thus, several different glycan......The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba...

  10. Perceived HIV-associated stigma among HIV-seropositive men: psychometric study of HIV stigma scale

    Directory of Open Access Journals (Sweden)

    Adrian eValle

    2015-07-01

    Full Text Available Objectives: To assess the internal consistency and factor structure of the abridged Spanish version of the Berger HIV Stigma Scale (HSS-21, provide evidence for its convergent and discriminant validity, and describe perceived stigma in an urban population from northeast Mexico. Methods: Seventy five HIV-positive men who have sex with men (MSM were recruited. Participants answered the Spanish versions of three Likert-type scales: HSS-21, Robsenberg’s self-esteem scale, and the abbreviated version of the Zung’s Depression Scale.Results: HSS-21 showed high reliability and validity; its factor structure included four components: concern with public attitudes; negative self-image; disclosure concerns; and enacted stigma. The level of stigma was high in 27 out of 75 (36% participants; nevertheless, the score found in the component related to disclosure concerns indicated high level of stigma in 68% of participants. The score of HSS-21 was positively correlated with the score of depression and negatively correlated with the score of self-esteem. Conclusion: Results demonstrated high reliability for the HSS-21; correlations with other scales supported its validity. This scale demonstrated to be a practical tool for assessing stigma among Mexican HIV-positive MSM. High level of stigma was found only in the factor related to disclosure concerns. Policy Implications: Identifying HIV-associated stigma through a short, reliable and validated instrument will allow the development of interventions that cope and manage stigma in HIV-positive MSM. HSS-21 distinguishes between different dimensions of stigma and will contribute to a better understanding of this phenomenon.

  11. Nanotechnology applications to HIV vaccines and microbicides

    Directory of Open Access Journals (Sweden)

    Sandhya Boyapalle

    2012-01-01

    Full Text Available Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS remains one of the most serious threats to global health. Today there are no HIV vaccines which can prevent HIV infection. All of the candidates being studied are in the experimental stage. Preventive vaccine candidates are being tested in HIV-negative people to see if they can prevent infection. With of the development of a safe and effective vaccine still likely to be years away, topical microbicide formulations that are applied vaginally and rectally are receiving greater interest as an effective alternative to slow down the global spread of HIV. Current microbicide trials that aim to prevent the sexual transmission of HIV are using gels, creams, rings, films and there is also work underway to explore other types of ′delivery′ systems. There have been numerous reports on safety and lack of toxicity of the application of nanotechnology for targeted delivery and slow, sustained release of drugs, proteins, peptides or nucleic acids by any route to maximize effectiveness and minimize adverse effects. The application of nanotechnology for targeting drugs and macromolecules to specific tissues or cells is one of the most important areas in nanomedicine research. Thus far nanoparticles provide a strong platform to combine protein and DNA based vaccines/microbicides and will facilitate the production, preclinical evaluation and clinical testing in the future.

  12. MTV's "Staying Alive" global campaign promoted interpersonal communication about HIV and positive beliefs about HIV prevention.

    Science.gov (United States)

    Geary, Cynthia Waszak; Burke, Holly McClain; Castelnau, Laure; Neupane, Shailes; Sall, Yacine Ba; Wong, Emily; Tucker, Heidi Toms

    2007-02-01

    In 2002 MTV launched a global multicomponent HIV prevention campaign, "Staying Alive," reaching over 166 countries worldwide. An evaluation of this campaign focused on three diverse sites: Kathmandu, Nepal; São Paulo, Brazil; and Dakar, Senegal. Data were collected before and after campaign implementation through population-based household surveys. Using linear regression techniques, our evaluation examined the effects of campaign exposure on interpersonal communication about HIV and the effects of campaign exposure and interpersonal communication on beliefs about HIV prevention. We found a consistent positive effect of exposure on interpersonal communication across all sites, though there were differences among sites with regard to whom the respondent talked about HIV. We also found a consistent positive effect of exposure on HIV prevention beliefs across sites when interpersonal communication was simultaneously entered into the model. Finally, in two sites we found a relationship between interpersonal communication and HIV prevention beliefs, controlling for exposure, though again, the effects differed by the type of person the communication was with. These similar findings in three diverse sites provide ecological validity of the findings that "Staying Alive" promoted interpersonal communication and influenced young people's beliefs about HIV prevention in a positive way, evidence for the potential of a global media campaign to have an impact on social norms.

  13. HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

    Science.gov (United States)

    Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

    2010-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

  14. NF45 and NF90 Bind HIV-1 RNA and Modulate HIV Gene Expression

    Directory of Open Access Journals (Sweden)

    Yan Li

    2016-02-01

    Full Text Available A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45 and nuclear factor 90 (NF90 as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1 replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 and NF90 diminished the enhancement of HIV infection and gene expression. Both proteins were found to interact with the HIV RNA. RNA decay assays demonstrated that NF90, but not NF45, increased the half-life of the HIV RNA. Overall, these studies indicate that both NF45 and NF90 potentiate HIV infection through their RNA binding domains.

  15. Virus-Specific Cytotoxic T Lymphocytes in Human Immunodeficiency Virus Type 1-Infected Chimpanzees

    OpenAIRE

    Santra, Sampa; Fultz, Patricia N.; Letvin, Norman L.

    1999-01-01

    Chimpanzees have been important in studies of human immunodeficiency virus type 1 (HIV-1) pathogenesis and in evaluation of HIV-1 candidate vaccines. However, little information is available about HIV-1-specific cytotoxic T lymphocytes (CTL) in these animals. In the present study, in vitro stimulation of peripheral blood mononuclear cells (PBMC) from infected chimpanzees with HIV-1 Gag peptides was shown to be a sensitive, reproducible method of expanding HIV-1-specific CD8+ effector CTL. Of ...

  16. Sero- and Molecular Epidemiology of HIV-1 in Papua Province, Indonesia

    Directory of Open Access Journals (Sweden)

    Muhammad Qushai Yunifiar M

    2017-11-01

    Full Text Available Background: human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS cause serious health problems and affect the Indonesian economy. Papua province has the highest prevalence of HIV infection in the country; however, epidemiological data are limited. Therefore, in order to reveal the current situation of HIV/AIDS in Papua province, sero- and molecular epidemiological studies of HIV were conducted. Methods: serological tests were conducted on 157 healthy individuals from the general population residing in Paniai, Papua. In addition, a molecular epidemiological study was then conducted on HIV type 1 (HIV-1 genes derived from infected individuals. Peripheral blood samples from HIV-1-positive individuals and 15 additionally enrolled, previously confirmed HIV-1-positive individuals were subjected to a genotypic analysis. Results: serological tests revealed that 2 out of 157 (1.27% healthy individuals were HIV-positive. In addition, HIV-1 subtyping revealed that subtype B and CRF01_AE were the major subtype and circulating recombinant form (CRF of HIV-1 prevalent in the region, while subtype A1 and a recombinant form including viral gene fragments of CRF01_AE and subtype B was also detected. In addition, HIV drug resistance-associated major mutations were detected in the reverse transcriptase gene derived from infected individual on antiretroviral therapy. Conclusion: these results provide important information for clearer understanding on the current situation of HIV/AIDS in Papua province in Indonesia.

  17. Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells.

    Directory of Open Access Journals (Sweden)

    Sekar Natesampillai

    2010-11-01

    Full Text Available In medicine, understanding the pathophysiologic basis of exceptional circumstances has led to an enhanced understanding of biology. We have studied the circumstance of HIV-infected patients in whom antiretroviral therapy results in immunologic benefit, despite virologic failure. In such patients, two protease mutations, I54V and V82A, occur more frequently. Expressing HIV protease containing these mutations resulted in less cell death, caspase activation, and nuclear fragmentation than wild type (WT HIV protease or HIV protease containing other mutations. The impaired induction of cell death was also associated with impaired cleavage of procaspase 8, a requisite event for HIV protease mediated cell death. Primary CD4 T cells expressing I54V or V82A protease underwent less cell death than with WT or other mutant proteases. Human T cells infected with HIV containing these mutations underwent less cell death and less Casp8p41 production than WT or HIV containing other protease mutations, despite similar degrees of viral replication. The reductions in cell death occurred both within infected cells, as well as in uninfected bystander cells. These data indicate that single point mutations within HIV protease which are selected in vivo can significantly impact the ability of HIV to kill CD4 T cells, while not impacting viral replication. Therefore, HIV protease regulates both HIV replication as well as HIV induced T cell depletion, the hallmark of HIV pathogenesis.

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune deficiency syndrome). AIDS ... but no cure, at the present time. The virus (HIV) and the disease it causes (AIDS) are ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/ . Reference Centers for Disease ... About HIV/AIDS. ( https://www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, GA: CDC, DHHS. Retrieved November ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Education Projects » Learn the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter ... research findings and news updates. Read on to Learn the Link between drug use and HIV and ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... public discussions on using new media effectively in response to HIV/AIDS, as well as HIV/AIDS ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV infection in the United States. Drugs can change the way the brain works, disrupting the ... linked and referred to as "HIV/AIDS." HIV can be transferred between people if an infected person's ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, and ...

  4. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved June 2012 How are Drug Abuse and HIV Related? Drug abuse and addiction ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Misuse and HIV Related? Drug misuse and addiction have been linked with HIV/AIDS since the beginning ... the link between drug misuse and HIV. We have produced a set of multicultural public service announcements ( ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... by HIV/AIDS, and the general public. U.S. National Library of Medicine HIV/AIDS Information : Specialized Information Services. VA National HIV/AIDS : This site provides information both for ...

  8. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... between drug abuse and HIV/AIDS. In the early years of the HIV epidemic, it became clear ... HIV/AIDS and the discovery of promising treatment interventions for breaking the harmful links between them, we ...

  9. Women and HIV/AIDS

    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 ...

  10. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV to their babies during pregnancy, delivery, and breastfeeding. HIV destroys a certain kind of white blood ... brain. Research has shown that HIV causes greater injury to cells in the brain and cognitive impairment ...

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... behavior by altering judgment and decision-making. To learn about HIV among youth, please visit: http://www.cdc.gov/hiv/risk/age/youth/index.html​ . Resources Publications Drug Facts: HIV/ ...

  12. HIV, AIDS, and the Future

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV, AIDS, and the Future Past Issues / Summer 2009 ... turn Javascript on. Photo: The NAMES Project Foundation HIV and AIDS are a global catastrophe. While advances ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... access to the latest, federally approved HIV/AIDS medical practice guidelines, HIV treatment and prevention clinical trials, and other research information for health care providers, researchers, people affected by HIV/AIDS, and ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... effects of drugs. Drug abuse and addiction can affect a person's overall health, thereby altering susceptibility to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes ...

  15. The organization of HIV and other health activities within urban religious congregations.

    Science.gov (United States)

    Palar, Kartika; Mendel, Peter; Derose, Kathryn Pitkin

    2013-10-01

    Most religious congregations in the USA are involved with some type of social service activity, including health activities. However, relatively few formally engage with people with HIV, and many have reported barriers to introducing HIV prevention activities. We conducted a qualitative case study of HIV involvement among 14 urban congregations in Los Angeles County in 2007. In-depth qualitative interviews of lay leaders and clergy were analyzed for themes related to HIV and other health activities, including types of health issues addressed, types of activities conducted, how activities were organized, and the relationship between HIV and other health activities. We identified three primary models representing how congregations organized HIV and other health activities: (1) embedded (n = 7), where HIV activities were contained within other health activities; (2) parallel (n = 5), where HIV and other health activities occurred side by side and were organizationally distinct; (3) overlap (n = 2), where HIV and non-HIV health efforts were conducted by distinct groups, but shared some members and organization. We discuss implications of each model for initiating and sustaining HIV activities within urban congregations over time.

  16. Potential impact of viral load and genetic makeup of HIV type 1 on mother-to-child transmission: characterization of env-C2V3C3 and nef sequences.

    Science.gov (United States)

    Pádua, Elizabeth; Parreira, Ricardo; Tendeiro, Rita; Nunes, Baltazar; Castela, João; Soares, Isabel; Mouzinho, Ana; Reis, Eduarda; Paixão, Maria Teresa

    2009-11-01

    HIV-1 mother-to-child transmission (MTCT) was evaluated in terms of the molecular characterization of the env and nef genomic regions and quantification of maternal RNA viral loads. Assignment of viral subtype was achieved by direct sequencing of PCR 1172 products amplified from proviral DNA in 45 HIV-1-nontransmitting mothers (NTM), along with 13 pairs of HIV-1-transmitting mothers (TM) and their infected children (C). Analysis of the env C2V3C3 and nef sequences revealed that subtypes G and B, and their genetic combinations (AG, BG), accounted for over 84.5% of all viruses identified. The genetic structure form envA-nefG was the most commonly observed, with a lower frequency in the NTM (13.3%) compared to the TM (23.1%) group. A greater number of genetic forms was observed among NTM, namely the presence of sequences assigned to subtypes D and F, as well as the intergenetic A/J, and C/U, recombinant forms, along with a mosaic provirus with a complex putative envA-nefEGE genetic structure. No significant differences were found when RNA viral loads were evaluated as a function of the viral subtypes. Nevertheless, a relatively high quantification of HIV-1 RNA was obtained in the NTM group, emphasizing the importance of the compliance and effectiveness of therapeutic schemes to control viral replication and reduce the risk of HIV vertical transmission. V3 sequences displaying features associated with the R5 phenotype dominated in both groups. Both C2V3C3 and Nef's functional domains were conserved during HIV-1 vertical transmission.

  17. Higher prevalence of oral human papillomavirus infection in HIV-positive than HIV-negative Thai men and women.

    Science.gov (United States)

    Vacharotayangul, Piamkamon; Rungsiyanont, Sorasun; Lam-Ubol, Aroonwan; Pankam, Tippawan; Rodbamrung, Piyanee; Naorungroj, Supawadee; Phanuphak, Nittaya

    2015-12-01

    This study was designed to investigate the prevalence of oral human papillomavirus (HPV) infection among HIV-positive and HIV-negative Thai men and women. Participants including men who have sex with men (MSM) and heterosexual women were enrolled at the Thai Red Cross Anonymous Clinic in Bangkok. History taking and oral examination were performed by three independent dentists after calibration. HPV infection was evaluated from oral rinse with mouthwash collected at the time of examination. HPV typing was performed by PCR and nucleic acid hybridization to detect thirty-seven HPV DNA genotypes using Linear Array(®) HPV Genotyping Test (Roche Molecular System, Inc.). 244 subjects were enrolled in the study, consisted of 187 HIV-positive (51.9% women and 48.1% MSM) and 57 HIV-negative (21.0% women and 79.0% MSM) Thai subjects. The prevalence of oral HPV infection was 17.2% in HIV-positive subjects whereas only 5.3% of HIV-negative cases had HPV detected in their oral rinses (p=0.0346). Among HIV positive subjects, MSM had higher chance of having HPV infection than females (25% vs. 9.4%, p=0.0074). HIV-positive Thai MSM and women had higher prevalence of oral HPV infection than those without HIV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. [Incidence of cancer in Chilean HIV-infected children].

    Science.gov (United States)

    Vlllarroel, Julia; Álvarez, Ana M; Chávez, Ana; Cofré, José; Galaz, M Isabel; Ledesma, Patricio; Peña, Anamaría; Vizueta, Eloisa; Wu, Elba

    2015-12-01

    Pediatric HIV (+) patients have a 100 times greater risk of cancer than HIV (-) children. To describe in Chilean HIV (+) children, cancer types, its appearance in relation to the stages of HIV disease and mortality. A protocol was created to know some characteristics of these patients from the point of view of their HIV infection and cancer pathology. Of 360 HIV (+) children confirmed by the Institute of Public Health to May 2014, 9 patients with neoplastic disease (2.5%) were diagnosed. All the children were on ART, had more than three years of evolution of HIV infection and were in moderate to severe clinical/immunological stages. Lymphoma was the most common cancer. Five children, has received therapy according to Programa Infantil Nacional de Drogas Antineoplásicas (PINDA). There was no interaction between cancer treatment and antiretroviral therapy. Mortality was 13.8 x 1000 (5 cases). The incidence and type of neoplasia is consistent with the international literature, with less survival than HIV (+) children without tumors. The occurrence of cancer was observed in children with moderate to severe clinical and immunological compromise.

  19. CD26/dipeptidyl peptidase IV (CD26/DPPIV is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

    Directory of Open Access Journals (Sweden)

    Meyers Adrienne FA

    2010-11-01

    Full Text Available Abstract Background Design of effective vaccines against the human immunodeficiency virus (HIV-1 continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway. Results A quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV + and 100 HIV negative controls (HIV Neg showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml than the HIV Neg (910 ng/ml and HIV + (870 ng/ml, p Conclusion HIV resistant sex workers have a high expression of CD26/DPPIV in tandem with lowered immune activation markers. This may suggest a novel role for CD26/DPPIV in protection against HIV infection in vivo.

  20. Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

    Science.gov (United States)

    Jespersen, Sanne; Hønge, Bo Langhoff; Esbjörnsson, Joakim; Medina, Candida; da Silva Té, David; Correira, Faustino Gomes; Laursen, Alex Lund; Østergaard, Lars; Andersen, Andreas; Aaby, Peter; Erikstrup, Christian; Wejse, Christian

    2016-02-01

    Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients. This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models. A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/μl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39). Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women. © 2015 John Wiley & Sons Ltd.