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Sample records for cell count-guided antiretroviral

  1. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up

    DEFF Research Database (Denmark)

    Lundgren, Jens; Babiker, Abdel; El-Sadr, Wafaa

    2008-01-01

    BACKGROUND AND METHODS: The SMART study compared 2 strategies for using antiretroviral therapy-drug conservation (DC) and viral suppression (VS)-in 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL. Rates and predictors of opportunistic disease...... or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported. RESULTS: During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count ...%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow- up with a CD4+ cell count

  2. CD4+ Count-Guided Interruption of Antiretroviral Treatment. The Strategies for Mangement of Antiretroviral Therapy (SMART) Study Group

    DEFF Research Database (Denmark)

    El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD

    2006-01-01

    had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less......BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who...... the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society....

  3. CD4+ Count-Guided Interruption of Antiretroviral Treatment. The Strategies for Mangement of Antiretroviral Therapy (SMART) Study Group

    DEFF Research Database (Denmark)

    El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD

    2006-01-01

    BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV wh...

  4. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Carr, Andrew; Neuhaus, Jacquie

    2008-01-01

    BACKGROUND: The SMART trial found a raised risk of cardiovascular disease (CVD) events in patients undergoing CD4+ T cell-count guided intermittent antiretroviral therapy (ART) compared with patients on continuous ART. Exploratory analyses were performed to better understand the reasons for this ...

  5. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

    Directory of Open Access Journals (Sweden)

    Balkundi S

    2011-12-01

    Full Text Available Shantanu Balkundi1, Ari S Nowacek1, Ram S Veerubhotla1, Han Chen2, Andrea Martinez-Skinner1, Upal Roy1, R Lee Mosley1,3, Georgette Kanmogne1, Xinming Liu1,3,4, Alexander V Kabanov3,4, Tatiana Bronich3,4, JoEllyn McMillan1, Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; 2Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA; 3Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.Keywords: human immunodeficiency virus type one, nanotoxicology, monocyte-derived macrophage, nanoformulated antiretroviral therapy, manufacturing techniques

  6. CD4 + CELL RESPONSE TO ANTI-RETROVIRAL THERAPY (ARTs ...

    African Journals Online (AJOL)

    enhances immunity by sustained HIV- viral suppression, increase in CD4+ cell count and immune restoration. ... Seventy three (70.9%) of patients still had immune depletion with low CD4+ cell counts at one year of receiving HAART. ..... homeostasis and function in advanced HIV disease. Science 1997; 277: 112- 116. 7.

  7. Different origin of adipogenic stem cells influences the response to antiretroviral drugs

    Energy Technology Data Exchange (ETDEWEB)

    Gibellini, Lara; De Biasi, Sara; Nasi, Milena; Carnevale, Gianluca; Pisciotta, Alessandra; Bianchini, Elena; Bartolomeo, Regina [Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia School of Medicine, Via Campi 287, 41125 Modena (Italy); Polo, Miriam [Department of Pharmacology, University of Valencia, Av.da Blasco Ibáñez 15, Valencia (Spain); FISABIO–Hospital Universitario Dr. Peset, Av.da Gaspar Aguilar 90, Valencia (Spain); De Pol, Anto [Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia School of Medicine, Via Campi 287, 41125 Modena (Italy); Dipartimento Sperimentale Interaziendale, Campus San Lazzaro, University of Modena and Reggio Emilia, 42122 Reggio Emilia (Italy); Pinti, Marcello [Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena (Italy); Cossarizza, Andrea, E-mail: andrea.cossarizza@unimore.it [Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia School of Medicine, Via Campi 287, 41125 Modena (Italy); Dipartimento Sperimentale Interaziendale, Campus San Lazzaro, University of Modena and Reggio Emilia, 42122 Reggio Emilia (Italy)

    2015-10-01

    Lipodystrophy (LD) is a main side effect of antiretroviral therapy for HIV infection, and can be provoked by nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). LD exists in different forms, characterized by fat loss, accumulation, or both, but its pathogenesis is still unclear. In particular, few data exist concerning the effects of antiretroviral drugs on adipocyte differentiation. Adipose tissue can arise either from mesenchymal stem cells (MSCs), that include bone marrow-derived MSCs (hBM-MSCs), or from ectodermal stem cells, that include dental pulp stem cells (hDPSCs). To analyze whether the embryonal origin of adipocytes might impact the occurrence of different phenotypes in LD, we quantified the effects of several antiretroviral drugs on the adipogenic differentiation of hBM-MSCs and hDPSCs. hBM-MSCs and hDPSCs were isolated from healthy donors. Cells were treated with 10 and 50 μM stavudine (d4T), efavirenz (EFV), atazanavir (ATV), ritonavir (RTV), and ATV-boosted RTV. Viability and adipogenesis were evaluated by staining with propidium iodide, oil red, and adipoRed; mRNA levels of genes involved in adipocyte differentiation, i.e. CCAAT/enhancer-binding protein alpha (CEBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), and in adipocyte functions, i.e. fatty acid synthase (FASN), fatty acid binding protein-4 (FABP4), perilipin-1 (PLIN1) and 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2), were quantified by real time PCR. We found that ATV, RTV, EFV, and ATV-boosted RTV, but not d4T, caused massive cell death in both cell types. EFV and d4T affected the accumulation of lipid droplets and induced changes in mRNA levels of genes involved in adipocyte functions in hBM-MSCs, while RTV and ATV had little effects. All drugs stimulated the accumulation of lipid droplets in hDPSCs. Thus, the adipogenic differentiation of human stem cells can be influenced by antiretroviral drugs, and depends, at least in

  8. Different origin of adipogenic stem cells influences the response to antiretroviral drugs

    International Nuclear Information System (INIS)

    Gibellini, Lara; De Biasi, Sara; Nasi, Milena; Carnevale, Gianluca; Pisciotta, Alessandra; Bianchini, Elena; Bartolomeo, Regina; Polo, Miriam; De Pol, Anto; Pinti, Marcello; Cossarizza, Andrea

    2015-01-01

    Lipodystrophy (LD) is a main side effect of antiretroviral therapy for HIV infection, and can be provoked by nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). LD exists in different forms, characterized by fat loss, accumulation, or both, but its pathogenesis is still unclear. In particular, few data exist concerning the effects of antiretroviral drugs on adipocyte differentiation. Adipose tissue can arise either from mesenchymal stem cells (MSCs), that include bone marrow-derived MSCs (hBM-MSCs), or from ectodermal stem cells, that include dental pulp stem cells (hDPSCs). To analyze whether the embryonal origin of adipocytes might impact the occurrence of different phenotypes in LD, we quantified the effects of several antiretroviral drugs on the adipogenic differentiation of hBM-MSCs and hDPSCs. hBM-MSCs and hDPSCs were isolated from healthy donors. Cells were treated with 10 and 50 μM stavudine (d4T), efavirenz (EFV), atazanavir (ATV), ritonavir (RTV), and ATV-boosted RTV. Viability and adipogenesis were evaluated by staining with propidium iodide, oil red, and adipoRed; mRNA levels of genes involved in adipocyte differentiation, i.e. CCAAT/enhancer-binding protein alpha (CEBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), and in adipocyte functions, i.e. fatty acid synthase (FASN), fatty acid binding protein-4 (FABP4), perilipin-1 (PLIN1) and 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2), were quantified by real time PCR. We found that ATV, RTV, EFV, and ATV-boosted RTV, but not d4T, caused massive cell death in both cell types. EFV and d4T affected the accumulation of lipid droplets and induced changes in mRNA levels of genes involved in adipocyte functions in hBM-MSCs, while RTV and ATV had little effects. All drugs stimulated the accumulation of lipid droplets in hDPSCs. Thus, the adipogenic differentiation of human stem cells can be influenced by antiretroviral drugs, and depends, at least in

  9. A Subset of CD4/CD8 Double-Negative T Cells Expresses HIV Proteins in Patients on Antiretroviral Therapy

    NARCIS (Netherlands)

    DeMaster, Laura K.; Liu, Xiaohe; VanBelzen, D. Jake; Trinité, Benjamin; Zheng, Lingjie; Agosto, Luis M.; Migueles, Stephen A.; Connors, Mark; Sambucetti, Lidia; Levy, David N.; Pasternak, Alexander O.; O'Doherty, Una

    2016-01-01

    A major goal in HIV eradication research is characterizing the reservoir cells that harbor HIV in the presence of antiretroviral therapy (ART), which reseed viremia after treatment is stopped. In general, it is assumed that the reservoir consists of CD4(+) T cells that express no viral proteins.

  10. Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Programs

    NARCIS (Netherlands)

    Anderegg, Nanina; Panayidou, Klea; Abo, Yao; Alejos, Belen; Althoff, Keri N.; Anastos, Kathryn; Antinori, Andrea; Balestre, Eric; Becquet, Renaud; Castagna, Antonella; Castelnuovo, Barbara; Chêne, Geneviève; Coelho, Lara; Collins, Intira Jeannie; Costagliola, Dominique; Crabtree-Ramírez, Brenda; Dabis, Francois; D'Arminio Monforte, Antonella; Davies, Mary-Ann; de Wit, Stéphane; Delpech, Valérie; de La Mata, Nicole L.; Duda, Stephany; Freeman, Aimee; Gange, Stephen J.; Grabmeier-Pfistershammer, Katharina; Gunsenheimer-Bartmeyer, Barbara; Jiamsakul, Awachana; Kitahata, Mari M.; Law, Matthew; Manzardo, Christian; McGowan, Catherine; Meyer, Laurence; Moore, Richard; Mussini, Cristina; Nakigoz, Gertrude; Nash, Denis; tek Ng, Oon; Obel, Niels; Pantazis, Nikos; Poda, Armel; Raben, Dorthe; Reiss, Peter; Riggen, Larry; Sabin, Caroline; d'Amour Sinayobye, Jean; Sönnerborg, Anders; Stoeckle, Marcel; Thorne, Claire; Torti, Carlo

    2018-01-01

    Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income,

  11. 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.

  12. Nutritional status and CD4 cell counts in patients with HIV/AIDS receiving antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Ana Celia Oliveira dos Santos

    2013-12-01

    Full Text Available Introduction Even with current highly active antiretroviral therapy, individuals with AIDS continue to exhibit important nutritional deficits and reduced levels of albumin and hemoglobin, which may be directly related to their cluster of differentiation 4 (CD4 cell counts. The aim of this study was to characterize the nutritional status of individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS and relate the findings to the albumin level, hemoglobin level and CD4 cell count. Methods Patients over 20 years of age with AIDS who were hospitalized in a university hospital and were receiving antiretroviral therapy were studied with regard to clinical, anthropometric, biochemical and sociodemographic characteristics. Body mass index, percentage of weight loss, arm circumference, triceps skinfold and arm muscle circumference were analyzed. Data on albumin, hemoglobin, hematocrit and CD4 cell count were obtained from patient charts. Statistical analysis was performed using Fisher's exact test, Student's t-test for independent variables and the Mann-Whitney U-test. The level of significance was set to 0.05 (α = 5%. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS 17.0 software for Windows. Results Of the 50 patients evaluated, 70% were male. The prevalence of malnutrition was higher when the definition was based on arm circumference and triceps skinfold measurement. The concentrations of all biochemical variables were significantly lower among patients with a body mass index of less than 18.5kg/m2. The CD4 cell count, albumin, hemoglobin and hematocrit anthropometric measures were directly related to each other. Conclusions These findings underscore the importance of nutritional follow-up for underweight patients with AIDS, as nutritional status proved to be related to important biochemical alterations.

  13. Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

    Science.gov (United States)

    Kevadiya, Bhavesh D.; Woldstad, Christopher; Ottemann, Brendan M.; Dash, Prasanta; Sajja, Balasrinivasa R.; Lamberty, Benjamin; Morsey, Brenda; Kocher, Ted; Dutta, Rinku; Bade, Aditya N.; Liu, Yutong; Callen, Shannon E.; Fox, Howard S.; Byrareddy, Siddappa N.; McMillan, JoEllyn M.; Bronich, Tatiana K.; Edagwa, Benson J.; Boska, Michael D.; Gendelman, Howard E.

    2018-01-01

    RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models. METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution. RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate. CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy. PMID:29290806

  14. CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Phillips, Andrew N; Gatell, Jose

    2013-01-01

    CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study...

  15. Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

    Directory of Open Access Journals (Sweden)

    Dina Tsukrov

    2016-09-01

    Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

  16. T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Caroline C Chisenga

    Full Text Available To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART, and to assess the impact of a nutritional intervention on T-cell subsets.This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test.Among 181 adults, 36 (20% died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group.Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention.

  17. In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

    CSIR Research Space (South Africa)

    Malabi, Rudzani

    2017-01-01

    Full Text Available . Therapeutic targeting of HIV therefore requires further investigation and current therapies need modification in order to address HIV eradication. This deflects research towards investigating potential novel antiretroviral drug delivery systems. The use...

  18. Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model

    Science.gov (United States)

    Chatterjee, Aparajita; Ratner, Daniel M.; Ryan, Christopher M.; Johnson, Patricia J.; O’Keefe, Barry R.; Secor, W. Evan; Anderson, Deborah J.; Robbins, Phillips W.; Samuelson, John

    2015-01-01

    Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans), like those of HIV, bind the mannose-binding lectin (MBL) that is part of the innate immune system. N-glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin) and the 2G12 monoclonal antibody, each of which binds HIV N-glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas. Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N-glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas. PMID:26252012

  19. Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model.

    Directory of Open Access Journals (Sweden)

    Aparajita Chatterjee

    Full Text Available Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans, like those of HIV, bind the mannose-binding lectin (MBL that is part of the innate immune system. N-glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin and the 2G12 monoclonal antibody, each of which binds HIV N-glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas. Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N-glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas.

  20. T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy.

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    Allison S Thomas

    2017-09-01

    Full Text Available HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART, these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18. Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that

  1. Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-09-06

    CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

  2. Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

    NARCIS (Netherlands)

    Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Steingrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, José A. M.; Miedema, Frank

    2008-01-01

    It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

  3. Restoration of the CD4 T cell compartment after long-term highly active Antiretroviral therapy without phenotypical signs of accelerated immunological aging

    NARCIS (Netherlands)

    Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Stemgrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, Jose A. M.; Miedema, Frank

    2008-01-01

    It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

  4. No Neurocognitive Advantage for Immediate Antiretroviral Treatment in adults with greater than 500 CD4+ T Cell Counts

    DEFF Research Database (Denmark)

    Wright, Edwina J; Grund, Birgit; Robertson, Kevin R

    2018-01-01

    OBJECTIVE: To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with >500 CD4+ cells/μL. DESIGN: Randomized trial. METHODS: The START parent study randomized participants to commence immediate...... versus deferred ART until CD4+ cells/μL. The START Neurology substudy used 8 neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight...... test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. RESULTS: 592 participants had a median age of 34 years; median baseline CD4+ count of 629 cells...

  5. Estimated average annual rate of change of CD4(+) T-cell counts in patients on combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Phillips, Andrew N; Ledergerber, Bruno

    2010-01-01

    BACKGROUND: Patients receiving combination antiretroviral therapy (cART) might continue treatment with a virologically failing regimen. We sought to identify annual change in CD4(+) T-cell count according to levels of viraemia in patients on cART. METHODS: A total of 111,371 CD4(+) T-cell counts...... and viral load measurements in 8,227 patients were analysed. Annual change in CD4(+) T-cell numbers was estimated using mixed models. RESULTS: After adjustment, the estimated average annual change in CD4(+) T-cell count significantly increased when viral load was cells/mm(3), 95......% confidence interval [CI] 26.6-34.3), was stable when viral load was 500-9,999 copies/ml (3.1 cells/mm(3), 95% CI -5.3-11.5) and decreased when viral load was >/=10,000 copies/ml (-14.8 cells/mm(3), 95% CI -4.5--25.1). Patients taking a boosted protease inhibitor (PI) regimen had more positive annual CD4(+) T-cell...

  6. Which HIV-infected adults with high CD4 T-cell counts benefit most from immediate initiation of antiretroviral therapy?

    DEFF Research Database (Denmark)

    Molina, Jean-Michel; Grund, Birgit; Gordin, Fred

    2018-01-01

    BACKGROUND: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate trea...

  7. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Pillay, Deenan; Miners, Alec H

    2008-01-01

    BACKGROUND: In lower-income countries, WHO recommends a population-based approach to antiretroviral treatment with standardised regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Our aim was to study the potential consequenc...... laboratory monitoring-is currently the highest priority....

  8. Polymorphism in interleukin-7 receptor α gene is associated with faster CD4 T-cell recovery after initiation of combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Hartling, Hans J; Thørner, Lise W; Erikstrup, Christian

    2014-01-01

    OBJECTIVES: To investigate single-nucleotide polymorphisms (SNPs) in the gene encoding interleukin-7 receptor α (IL7RA) as predictors for CD4⁺ T-cell change after initiation of combination antiretroviral therapy (cART) in HIV-infected whites. DESIGN: SNPs in IL7RA were determined in the Danish HIV...

  9. Immune targeting of PD-1hi expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

    International Nuclear Information System (INIS)

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine; Venzon, David; Brocca-Cofano, Egidio; DiPasquale, Janet; Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit; Sui, Yongjun; Berzofsky, Jay A.; Liu, Linda; Langermann, Solomon; Robert-Guroff, Marjorie

    2013-01-01

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1 hi expressing T cells and Tregs in PBMCs, and PD-1 hi Tregs in lymph nodes. It transiently decreased expression of Ki67 and α 4 β 7 in PBMC CD4 + and CD8 + Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1 hi cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1 hi cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1 hi cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire

  10. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Venzon, David [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Brocca-Cofano, Egidio; DiPasquale, Janet [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit [Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States); Sui, Yongjun; Berzofsky, Jay A. [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Liu, Linda; Langermann, Solomon [Amplimmune Inc., Gaithersburg, MD 20878 (United States); Robert-Guroff, Marjorie, E-mail: guroffm@mail.nih.gov [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-15

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

  11. Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Anna C. Hearps

    2017-06-01

    Full Text Available Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART. We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here, we analyzed a cohort of HIV+ men who have sex with men (MSM, n = 20 at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15 to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69+ and late (HLA-DR+/CD38+ activation were elevated in cART-naïve HIV+ MSM (p = 0.004 and 0.015, respectively, as were FcRγ− NK cells (p = 0.003. Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ− NK cells (p = 0.115 or activated HLA-DR+/CD38+ NK cells (p = 0.129 but did reduce T cell and monocyte activation (p < 0.001 for all. Proportions of FcRγ− NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56dim FcRγ− NK cell expansion and immune activation in HIV+ individuals. While proportions of activated CD69+ NK cells declined significantly on cART (p = 0.003, the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56dim FcRγ− NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV+ individuals on cART.

  12. Intestinal Parasitosis in Relation to Anti-Retroviral Therapy, CD4(+) T-cell Count and Diarrhea in HIV Patients.

    Science.gov (United States)

    Khalil, Shehla; Mirdha, Bijay Ranjan; Sinha, Sanjeev; Panda, Ashutosh; Singh, Yogita; Joseph, Anju; Deb, Manorama

    2015-12-01

    Intestinal parasitic infections are one of the major causes of diarrhea in human immunodeficiency virus (HIV) seropositive individuals. Antiretroviral therapy has markedly reduced the incidence of many opportunistic infections, but parasite-related diarrhea still remains frequent and often underestimated especially in developing countries. The present hospital-based study was conducted to determine the spectrum of intestinal parasitosis in adult HIV/AIDS (acquired immunodeficiency syndrome) patients with or without diarrhea with the levels of CD4(+) T-cell counts. A total of 400 individuals were enrolled and were screened for intestinal parasitosis. Of these study population, 200 were HIV seropositives, and the remaining 200 were HIV uninfected individuals with or without diarrhea. Intestinal parasites were identified by using microscopy as well as PCR assay. A total of 130 (32.5%) out of 400 patients were positive for any kinds of intestinal parasites. The cumulative number of parasite positive patients was 152 due to multiple infections. A significant association of Cryptosporidium (P<0.001) was detected among individuals with CD4(+) T-cell counts less than 200 cells/μl.

  13. Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study

    DEFF Research Database (Denmark)

    Lodwick, Rebecca K; Sabin, Caroline A; Porter, Kholoud

    2010-01-01

    Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries.......Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries....

  14. No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts.

    Science.gov (United States)

    Wright, Edwina J; Grund, Birgit; Robertson, Kevin R; Cysique, Lucette; Brew, Bruce J; Collins, Gary L; Poehlman-Roediger, Mollie; Vjecha, Michael J; Penalva de Oliveira, Augusto César; Standridge, Barbara; Carey, Cate; Avihingsanon, Anchalee; Florence, Eric; Lundgren, Jens D; Arenas-Pinto, Alejandro; Mueller, Nicolas J; Winston, Alan; Nsubuga, Moses S; Lal, Luxshimi; Price, Richard W

    2018-05-15

    To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/μl. Randomized trial. The START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/μl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. The 592 participants had a median age of 34 years; median baseline CD4 count was 629 cells/μl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P < 0.001 for increase from baseline). We observed substantial improvement in neurocognitive test performance during the first year in both study arms, underlining the importance of using a control group in studies assessing neurocognitive performance over time. Immediate ART neither benefitted nor harmed neurocognitive performance in individuals with CD4 cell counts above 500 cells/μl.

  15. Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Pedersen, Court; Madsen, Helle D

    2017-01-01

    A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was ......A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis...... tests demonstrated severely reduced lung capacity with an obstructive pattern and a moderately reduced diffusion capacity. High resolution computer tomography revealed minor areas with tree-in-bud pattern and no signs of air trapping on expiratory views. Lung biopsy showed lymphocytic infiltration...

  16. Primary cutaneous b-cell lymphoma successfully treated with highly active antiretroviral therapy alone: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    María F Villafañe

    2011-01-01

    Full Text Available Cutaneous B-cell lymphoma (CBCL is an unusual skin neoplasm with a great range of clinical presentations. Here, we report a case of CBCL in an AIDS patient presented as a single and nodular/ulcerative lesion in the perianal area. The patient was started on highly active antiretroviral therapy alone with a good clinical and oncological response. Two years later, the patient is asymptomatic with undetectable viral load and immune reconstitution.

  17. Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

    Science.gov (United States)

    Verhoeven, D; Sankaran, S; Dandekar, S

    2007-08-01

    Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

  18. Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-02-01

    The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

  19. Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals.

    Science.gov (United States)

    Banga, Riddhima; Procopio, Francesco A; Ruggiero, Alessandra; Noto, Alessandra; Ohmiti, Khalid; Cavassini, Matthias; Corpataux, Jean-Marc; Paxton, William A; Pollakis, Georgios; Perreau, Matthieu

    2018-01-01

    We recently demonstrated that lymph nodes (LNs) PD-1 + /T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investigated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1 + CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1 + CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment containing inducible replication competent virus in treated aviremic HIV-infected individuals.

  20. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  1. In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

    CSIR Research Space (South Africa)

    Malabi, Rudzani

    2017-01-01

    Full Text Available The objectives of this study are to use femtosecond laser pulses in a photo-translocation system to deliver ARVs into HIV infected TZMbl cells, and to investigate the influence of ARVs and laser on cellular processes using different molecular...

  2. When to start antiretroviral therapy

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred M

    2013-01-01

    Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it rema...

  3. Maternal CD4+ cell count decline after interruption of antiretroviral prophylaxis for the prevention of mother-to-child transmission of HIV.

    Science.gov (United States)

    Ekouevi, Didier; Abrams, Elaine J; Schlesinger, Malka; Myer, Landon; Phanuphak, Nittaya; Carter, Rosalind J

    2012-01-01

    We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program. Analysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm(3) at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ cells/mm(3) or cells/mm(3) at 24 months. Weibull regression was used for multivariable analysis. A total of 1,393 women with enrollment CD4+ ≥250 cells/mm(3) initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23-30), median CD4+ was 469 cells/mm(3) (IQR: 363-613). At 24 months post-delivery, the cumulative probability of CD4+ decline to cells/mm(3) was 12% (95% CI: 10-14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ cells/mm(3) was 28%; (95% CI: 25-32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to cells/mm(3): 46% (CD4+400-499 cells/mm(3)) vs. 19% (CD4+ ≥500 cells/mm(3)). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to cells/mm(3) within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5-3.2, pcell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.

  4. Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals

    DEFF Research Database (Denmark)

    Tauriainen, Johanna; Scharf, Lydia; Frederiksen, Juliet

    2017-01-01

    HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory...... and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T...... increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality...

  5. Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies

    NARCIS (Netherlands)

    Wolbers, Marcel; Babiker, Abdel; Sabin, Caroline; Young, Jim; Dorrucci, Maria; Chêne, Geneviève; Mussini, Cristina; Porter, Kholoud; Bucher, Heiner C.; del Amo, Julia; Meyer, Laurence; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Darbyshire, Janet; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kaldor, John; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Hamouda, Osamah; Kucherer, Claudia; Pantazis, Nikos; Hatzakis, Angelos; Paraskevis, Dimitrios; Karafoulidoua, Anastasia; van der Helm, Jannie; Geskus, Ronald; Schuitemaker, Hanneke

    2010-01-01

    BACKGROUND: CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the

  6. Thymic Output and CD4 T-Cell Reconstitution in HIV-Infected Children on Early and Interrupted Antiretroviral Treatment: Evidence from the Children with HIV Early Antiretroviral Therapy Trial

    Directory of Open Access Journals (Sweden)

    Joanna Lewis

    2017-09-01

    Full Text Available ObjectivesEarly treatment of HIV-infected children and adults is important for optimal immune reconstitution. Infants’ immune systems are more plastic and dynamic than older children’s or adults’, and deserve particular attention. This study aimed to understand the response of the HIV-infected infant immune system to early antiretroviral therapy (ART and planned ART interruption and restart.MethodsData from HIV-infected children enrolled the CHER trial, starting ART aged between 6 and 12 weeks, were used to explore the effect of ART on immune reconstitution. We used linear and non-linear regression and mixed-effects models to describe children’s CD4 trajectories and to identify predictors of CD4 count during early and interrupted ART.ResultsEarly treatment arrested the decline in CD4 count but did not fully restore it to the levels observed in HIV-uninfected children. Treatment interruption at 40 or 96 weeks resulted in a rapid decline in CD4 T-cells, which on retreatment returned to levels observed before interruption. Naïve CD4 T-cell count was an important determinant of overall CD4 levels. A strong correlation was observed between thymic output and the stable CD4 count both before and after treatment interruption.ConclusionEarly identification and treatment of HIV-infected infants is important to stabilize CD4 counts at the highest levels possible. Once stabilized, children’s CD4 counts appear resilient, with good potential for recovery following treatment interruption. The naïve T-cell pool and thymic production of naive cells are key determinants of children’s CD4 levels.

  7. Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Jesse J R Masson

    Full Text Available Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP and reactive oxygen species (ROS production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1 and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection.

  8. Engaging HIV-infected patients in antiretroviral therapy services: CD4 cell count testing after HIV diagnosis from 2005 to 2009 in Yunnan and Guangxi, China

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yao; Ray Y. Chen; ZHANG Fu-jie; LU Lin; LI Hui-qin; LIU Wei; TANG Zhi-rong; FANG Hua; Jennifer Y. Chen; MA Ye; ZHAO Yan

    2011-01-01

    Background The initiation and expansion of China's national free antiretroviral therapy program has led to significant improvement of survival among its participants. Success of further scaling up treatment coverage rests upon intensifying HIV screening and efficient linkage of care. Timely CD4 cell count testing after HIV diagnosis is necessary to determine whether a patient meets criteria for antiretroviral treatment, and represents a crucial link to engage HIV-infected patients in appropriate care, which has not been evaluated in China.Methods We evaluated all patients ≥16 years who tested HIV positive from 2005 to 2009 in Yunnan and Guangxi.Multivariate Logistic regression models were applied to identify factors associated with lack of CD4 cell count testing within 6 months after HIV diagnosis.Results A total of 83 556 patients were included. Over the study period, 30 635 (37%) of subjects received a CD4 cell count within 6 months of receiving the HIV diagnosis. The rate of CD4 cell count testing within 6 months of HIV diagnosis increased significantly from 7% in 2005 to 62% in 2009. Besides the earlier years of HIV diagnosis, negative predictors for CD4 cell count testing in multivariate analyses included older age, not married or unclear marriage status,incarceration, diagnosis at sexual transmitted disease clinics, mode of HIV transmission classified as men who have sex with men, intravenous drug users or transmission route unclear, while minority ethnicity, receipt of high school or higher education, diagnosis at voluntary counseling and testing clinics, and having HIV positive parents were protective.Conclusions Significant progress has been made in increasing CD4 testing among newly diagnosed HIV positive patients in Yunnan and Guangxi from 2005-2009. However, a sizable proportion of HIV positive patients still lack CD4testing within 6 months of diagnosis. Improving CD4 testing, particularly among patients with identified risk factors, is essential to

  9. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

    Science.gov (United States)

    Bouteloup, V; Sabin, C; Mocroft, A; Gras, L; Pantazis, N; Le Moing, V; d'Arminio Monforte, A; Mary-Krause, M; Roca, B; Miro, J M; Battegay, M; Brockmeyer, N; Berenguer, J; Morlat, P; Obel, N; De Wit, S; Fätkenheuer, G; Zangerle, R; Ghosn, J; Pérez-Hoyos, S; Campbell, M; Prins, M; Chêne, G; Meyer, L; Dorrucci, M; Torti, C; Thiébaut, R

    2017-01-01

    The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control. © 2016 British HIV Association.

  10. HIV-1 anti-retroviral drug effect on the C. albicans hyphal growth rate by a Bio-Cell Tracer system Efeito da droga anti-retroviral HIV-1 no crescimento de hifas de C. albicans monitoradas pelo sistema "Bio-Cell Tracer"

    Directory of Open Access Journals (Sweden)

    Nadja Rodrigues de Melo

    2006-09-01

    Full Text Available Declining incidence of oropharyngeal candidosis and opportunistic infections over recent years can be attributed to the use of highly active anti-retroviral therapy (HAART. Infection with C. albicans generally involves adherence and colonization of superficial tissues. During this process, budding yeasts are able to transform to hyphae and penetrate into the deep tissue. Using the biocell tracer system, C. albicans hyphal growth was dynamically observed at the cellular level. Ritonavir was effective in the inhibition of hyphal growth with growth rate of 0.8 mum/min. This study showed the in vitro effect of HIV anti-retroviral drug on the growth rate of the C. albicans hyphae.O declínio na incidência de candidose orofaríngea e infecções oportunistas associadas a infecção pelo HIV tem sido atribuído a introdução da terapia antiretroviral combinada (HAART. Infecção por C. albicans envolve aderência e colonização da mucosa superficial. Durante este processo leveduras são capazes de transformar-se na forma de hifas e penetrar nos tecidos mais profundos. Usando o sistema "Bio-Cell Tracer", o crescimento de hifas de C. albicans foi observado dinamicamente a nível celular. Ritonavir, inibidor de protease do HIV, foi efetivo na inibição do crescimento de hifas com media de 0.8 mim/min.O presente estudo demonstrou o efeito in vitro de um agente anti-retroviral HIV sobre o crescimento de hifas de C. albicans.

  11. Antiretroviral therapy: current drugs.

    Science.gov (United States)

    Pau, Alice K; George, Jomy M

    2014-09-01

    The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

  12. Determination of eligibility to antiretroviral therapy in resource ...

    African Journals Online (AJOL)

    admin

    Objective: This study was to determine eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte .... ART until CD4+ T cell counts fall below 200 cells/mm3 ... (Abbott Cell Dyne Operators manual) were checked for.

  13. Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.

    Science.gov (United States)

    Cummins, Nathan W; Rizza, Stacey; Litzow, Mark R; Hua, Stephane; Lee, Guinevere Q; Einkauf, Kevin; Chun, Tae-Wook; Rhame, Frank; Baker, Jason V; Busch, Michael P; Chomont, Nicolas; Dean, Patrick G; Fromentin, Rémi; Haase, Ashley T; Hampton, Dylan; Keating, Sheila M; Lada, Steven M; Lee, Tzong-Hae; Natesampillai, Sekar; Richman, Douglas D; Schacker, Timothy W; Wietgrefe, Stephen; Yu, Xu G; Yao, Joseph D; Zeuli, John; Lichterfeld, Mathias; Badley, Andrew D

    2017-11-01

    Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

  14. Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study

    DEFF Research Database (Denmark)

    Lodwick, Rebecca K; Sabin, Caroline A; Porter, Kholoud

    2010-01-01

    Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries....

  15. Trends in and correlates of CD4+ cell count at antiretroviral therapy initiation after changes in national ART guidelines in Rwanda

    Science.gov (United States)

    Mutimura, Eugene; Addison, Diane; Anastos, Kathryn; Hoover, Donald; Dusingize, Jean Claude; Karenzie, Ben; Izimukwiye, Isabelle; Mutesa, Leo; Nsanzimana, Sabin; Nashi, Denis

    2015-01-01

    Background Initiation of antiretroviral therapy (ART) in the advanced stages of HIV infection remains a major challenge in sub-Saharan Africa. This study was conducted to better understand barriers and enablers to timely ART initiation in Rwanda where ART coverage is high and national ART eligibility guidelines first expanded in 2007–2008. Methods Using data on 6326 patients (≥15 years) at five Rwandan clinics, we assessed trends and correlates of CD4+ cell count at ART initiation and the proportion initiating ART with advanced HIV disease (CD4+ Rwanda. However, sex disparities in late treatment initiation persisted through 2011–2012, and appeared to be driven by later diagnosis and/or delayed linkage to care among men. PMID:25562492

  16. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort

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    Colebunders Robert

    2011-02-01

    Full Text Available Abstract Background Antiretroviral therapy (ART partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods T-cell activation (CD38+HLA-DR+ and immune exhaustion (PD-1+ were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199 cells/μl], N = 34 ], optimal [282 (200-415 cells/μl, N = 64] and super-optimal [528 (416-878 cells/μl, N = 30]. Results Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+ was higher among suboptimal relative to optimal (P P = 0.022]. Conclusion T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.

  17. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients

    DEFF Research Database (Denmark)

    Bouteloup, V; Sabin, C; Mocroft, A

    2017-01-01

    OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research....... Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9...... and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on...

  18. HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4⁺ T-cell lymphocytes

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Boué, François

    2011-01-01

    The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4⁺ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected...... patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/μL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100,000 person-years, and similar on cART and not on cART (P...... = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/μL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases...

  19. Association between CD8 T-cell subsets and CD4/CD8 ratio with HS-CRP level in HIV-infected patients on antiretroviral therapy

    Science.gov (United States)

    Isabela, S.; Nugroho, A.; Harijanto, P. N.

    2018-03-01

    Due to improved access and adherence to antiretroviral therapy (ART), most HIV-infected persons worldwide are predicted to live longer. Nowadays the cause of death for most HIV-infected persons has changed to serious non-AIDS events (SNAEs) which is due to low-grade viremia. HIV patients with ART who had undergone CD4 cell count above 500/uL and there is an increase in hs-CRP despite an undetectable viral load. Some conditions CD8 cells count do not decrease with CD4 cells repairs. We researched in Prof Kandou General Hospital with a total sample of 35 HIV patients who had received ART with the level of CD4>350/uL. CD8 levels, CD4/CD8 ratio, and hs-CRP were assessed. This research is analytic descriptive with cross-sectional study design and analysis uses Spearman correlation. The mean CD8 during the study was 1291.8 (IQR 319-2610cells/uL), the mean ratio of CD4:CD8 was 0.57 (IQR 0.16-1.24) and median hs-CRP is 2.18 (IQR 0.3-6.6mg/dL). There was a significant positive correlation between CD8 and increased hs-CRP (r=0.369, pCD4/CD8 ratio and hs-CRP (r=-0.370, p<0.05).

  20. CD28-Negative CD4+ and CD8+ T Cells in Antiretroviral Therapy–Naive HIV-Infected Adults Enrolled in Adult Clinical Trials Group Studies

    Science.gov (United States)

    Tassiopoulos, Katherine; Landay, Alan; Collier, Ann C.; Connick, Elizabeth; Deeks, Steven G.; Hunt, Peter; Lewis, Dorothy E.; Wilson, Cara; Bosch, Ronald

    2012-01-01

    Background Individuals infected with human immunodeficiency virus (HIV) have higher risk than HIV-negative individuals for diseases associated with aging. T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks. Methods We measured the percentage of CD28−CD4+ and CD8+ T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group (ACTG) antiretroviral therapy (ART) studies and the ALLRT (ACTG Longitudinal Linked Randomized Trials) cohort, and from 48 HIV-negative adults. Pretreatment and 96-week posttreatment %CD28− cells were assessed using linear regression for associations with age, sex, race/ethnicity, CD4 count, HIV RNA, ART regimen, and hepatitis C virus (HCV) infection. Results In total, 1291 chronically HIV-infected adults were studied. Pretreatment, lower CD4 count was associated with higher %CD28−CD4+ and %CD28−CD8+ cells. For CD8+ cells, younger age and HCV infection were associated with a lower %CD28−. ART reduced %CD28− levels at week 96 among virally suppressed individuals. Older age was strongly predictive of higher %CD28−CD8+. Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher %CD28−. Conclusions Effective ART reduced the proportion of CD28− T cells. However, levels remained abnormally high and closer to levels in older HIV-uninfected individuals. This finding may inform future research of increased rates of age-associated disease in HIV-infected adults. PMID:22448010

  1. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.

    Science.gov (United States)

    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27 + CD21 - ) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27 + CD21 + ) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses ( APRIL, BTK, BLIMP1 ) and

  2. Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.

    Science.gov (United States)

    2000-07-07

    To determine if triple combination therapy, particularly including HIV protease inhibitors (PI), confers an unique immunological benefit that is independent of reductions of plasma viral load (pVL). The correlation between changes from baseline in CD4 cell count and pVL was examined at all time points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and INCAS) that compared dual nucleoside therapy with triple combination therapy. Individual pVL and CD4 cell counts changes from baseline were entered into multivariate linear regression models for patients receiving double therapy and for those receiving triple therapy including a PI and/or a non-nucleoside reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested. After 52 weeks of therapy, the relationship between changes from baseline CD4 cell count and pVL was independent of whether patients were assigned double or triple therapy (P = 0.23 and 0.69 for intercept and slope, respectively), or whether patients were assigned triple therapy including a PI or triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5% of patients ever had 'discordant' increases in both CD4 cell count and pVL compared with baseline, and this proportion was unrelated to the class of therapy used. 'Discordant' decreases from baseline in both parameters were observed in up to 35% of individuals. The correlation between pVL and CD4 cell count changes from baseline improved over time on therapy, regardless of the therapeutic regimen involved. The data provide no evidence for a CD4 cell count benefit of highly active antiretroviral therapy (HAART) unique to triple therapy or PI-containing regimens.

  3. Quasi-Poisson versus negative binomial regression models in identifying factors affecting initial CD4 cell count change due to antiretroviral therapy administered to HIV-positive adults in North-West Ethiopia (Amhara region).

    Science.gov (United States)

    Seyoum, Awoke; Ndlovu, Principal; Zewotir, Temesgen

    2016-01-01

    CD4 cells are a type of white blood cells that plays a significant role in protecting humans from infectious diseases. Lack of information on associated factors on CD4 cell count reduction is an obstacle for improvement of cells in HIV positive adults. Therefore, the main objective of this study was to investigate baseline factors that could affect initial CD4 cell count change after highly active antiretroviral therapy had been given to adult patients in North West Ethiopia. A retrospective cross-sectional study was conducted among 792 HIV positive adult patients who already started antiretroviral therapy for 1 month of therapy. A Chi square test of association was used to assess of predictor covariates on the variable of interest. Data was secondary source and modeled using generalized linear models, especially Quasi-Poisson regression. The patients' CD4 cell count changed within a month ranged from 0 to 109 cells/mm 3 with a mean of 15.9 cells/mm 3 and standard deviation 18.44 cells/mm 3 . The first month CD4 cell count change was significantly affected by poor adherence to highly active antiretroviral therapy (aRR = 0.506, P value = 2e -16 ), fair adherence (aRR = 0.592, P value = 0.0120), initial CD4 cell count (aRR = 1.0212, P value = 1.54e -15 ), low household income (aRR = 0.63, P value = 0.671e -14 ), middle income (aRR = 0.74, P value = 0.629e -12 ), patients without cell phone (aRR = 0.67, P value = 0.615e -16 ), WHO stage 2 (aRR = 0.91, P value = 0.0078), WHO stage 3 (aRR = 0.91, P value = 0.0058), WHO stage 4 (0876, P value = 0.0214), age (aRR = 0.987, P value = 0.000) and weight (aRR = 1.0216, P value = 3.98e -14 ). Adherence to antiretroviral therapy, initial CD4 cell count, household income, WHO stages, age, weight and owner of cell phone played a major role for the variation of CD4 cell count in our data. Hence, we recommend a close follow-up of patients to adhere the prescribed medication for

  4. Tenofovir-Based Highly Active Antiretroviral Therapy Is Associated with Superior CD4 T Cells Repopulation Compared to Zidovudine-Based HAART in HIV 1 Infected Adults

    Directory of Open Access Journals (Sweden)

    Vitus Sambo Badii

    2018-01-01

    Full Text Available Tenofovir-based highly active antiretroviral therapy (HAART is one of the preferred first-line therapies in the management of HIV 1 infection. Ghana has since 2014 adopted this recommendation; however there is paucity of scientific data that reflects the safety and efficacy of the tenofovir-based therapy compared to zidovudine in the Ghanaian health system. This study sought to assess the comparative immune reconstitution potential between tenofovir and zidovudine-based HAART regimens, which includes lamivudine and efavirenz in combination therapy. It also aimed to investigate the adverse drug reactions/events (ADREs associated with pharmacotherapy with these agents in a total of 106 HAART naïve HIV patients. The study included 80 patients in the tenofovir cohort while 26 patients were on the zidovudine regimen. The occurrence of HIV comorbidities profile was assessed at diagnosis and throughout the study period. The baseline CD4 T cells count of the participants was also assessed at diagnosis and repeated at a median period of five months (range 4–6 months, after commencing treatment with either tenofovir- or zidovudine-based HAART. After five months of the HAART, the tenofovir cohort recorded higher CD4 T cell count change from baseline compared to the zidovudine cohort (p<0.0001. The patients on the tenofovir-based HAART and female sex however appeared to be associated with more multiple ADREs.

  5. A baseline metabolomic signature is associated with immunological CD4+ T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients.

    Science.gov (United States)

    Rodríguez-Gallego, Esther; Gómez, Josep; Pacheco, Yolanda M; Peraire, Joaquim; Viladés, Consuelo; Beltrán-Debón, Raúl; Mallol, Roger; López-Dupla, Miguel; Veloso, Sergi; Alba, Verónica; Blanco, Julià; Cañellas, Nicolau; Rull, Anna; Leal, Manuel; Correig, Xavier; Domingo, Pere; Vidal, Francesc

    2018-03-13

    Poor immunological recovery in treated HIV-infected patients is associated with greater morbidity and mortality. To date, predictive biomarkers of this incomplete immune reconstitution have not been established. We aimed to identify a baseline metabolomic signature associated with a poor immunological recovery after antiretroviral therapy (ART) to envisage the underlying mechanistic pathways that influence the treatment response. This was a multicentre, prospective cohort study in ART-naive and a pre-ART low nadir (Immunological recovery was defined as reaching CD4 T-cell count at least 250 cells/μl after 36 months of virologically successful ART. We used univariate comparisons, Random Forest test and receiver-operating characteristic curves to identify and evaluate the predictive factors of immunological recovery after treatment. HIV-infected patients with a baseline metabolic pattern characterized by high levels of large high density lipoprotein (HDL) particles, HDL cholesterol and larger sizes of low density lipoprotein particles had a better immunological recovery after treatment. Conversely, patients with high ratios of non-HDL lipoprotein particles did not experience this full recovery. Medium very-low-density lipoprotein particles and glucose increased the classification power of the multivariate model despite not showing any significant differences between the two groups. In HIV-infected patients, a baseline healthier metabolomic profile is related to a better response to ART where the lipoprotein profile, mainly large HDL particles, may play a key role.

  6. Human Paraoxonase-1 Activity Is Related to the Number of CD4+ T-Cells and Is Restored by Antiretroviral Therapy in HIV-1-Infected Individuals

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    Luciana Morganti Ferreira Maselli

    2014-01-01

    Full Text Available Background. Paraoxonase-1 (PON1 activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1. We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART. Methods. PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve, and 509 were receiving HAART. HIV-1 infected individuals were treated with the following: efavirenz (EFV; n=195 or nevirapine (NVP; n=95 or lopinavir/ritonavir (LOP/r; n=219. Serum levels of total cholesterol (TC, HDL, and low-density lipoprotein (LDL fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios were determined. Results. PON1 activity (U/L was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (r=0,121; P=0,014. The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio in comparison with other groups. Conclusion. PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.

  7. Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy.

    Science.gov (United States)

    Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

    2015-06-01

    Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status. This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants. cART was associated with a monthly rise of 15.7 cells/μl (precovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. HIV-Specific ADCC Improves After Antiretroviral Therapy and Correlates With Normalization of the NK Cell Phenotype

    DEFF Research Database (Denmark)

    Jensen, Sanne S; Hartling, Hans J; Tingstedt, Jeanette L

    2015-01-01

    analyzed. RESULTS: The ability of NK cells to mediate ADCC was significantly increased after only 6 months of HAART and was not explained by a normalization of NK cell subsets (CD56 CD16 and CD56 CD16 NK cells) but rather by normalization in the frequency of NK cells expressing CCR7 and CD27...

  9. Validation of World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy and clinical predictors of low CD4 cell count in Uganda.

    Directory of Open Access Journals (Sweden)

    Steven Baveewo

    Full Text Available INTRODUCTION: The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3, it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3 or <350 cells/mm(3. OBJECTIVE: To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda. RESULTS: Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3% were classified as in stages 1 and 2 and 262 (68% were females. Participants had a mean age of 36.8 years (SD 8.5. We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3 and 350 cells/mm(3 was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2. CONCLUSION: The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.

  10. Resting regulatory CD4 T cells: a site of HIV persistence in patients on long-term effective antiretroviral therapy.

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    Tu-Anh Tran

    Full Text Available BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs (HLADR(-CD69(-CD25(hiFoxP3+CD4+ T cells purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging.

  11. Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing.

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    Datsen George Wei

    2014-04-01

    Full Text Available Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD, a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM compared with vorinostat (VOR; EC50 = 3,950 nM and other histone deacetylase (HDAC inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM. The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART, a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART.

  12. Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: effects on long-term T-cell reconstitution.

    Science.gov (United States)

    Lewis, Joanna; Walker, A Sarah; Castro, Hannah; De Rossi, Anita; Gibb, Diana M; Giaquinto, Carlo; Klein, Nigel; Callard, Robin

    2012-02-15

    Effective therapies and reduced AIDS-related morbidity and mortality have shifted the focus in pediatric human immunodeficiency virus (HIV) from minimizing short-term disease progression to maintaining optimal long-term health. We describe the effects of children's age and pre-antiretroviral therapy (ART) CD4 count on long-term CD4 T-cell reconstitution. CD4 counts in perinatally HIV-infected, therapy-naive children in the Paediatric European Network for the Treatment of AIDS 5 trial were monitored following initiation of ART for a median 5.7 years. In a substudy, naive and memory CD4 counts were recorded. Age-standardized measurements were analyzed using monophasic, asymptotic nonlinear mixed-effects models. One hundred twenty-seven children were studied. Older children had lower age-adjusted CD4 counts in the long term and at treatment initiation (P memory CD4 counts increased less, albeit on a faster timescale. It appears the immature immune system can recover well from HIV infection via the naive pool. However, this potential is progressively damaged with age and/or duration of infection. Current guidelines may therefore not optimize long-term immunological health.

  13. Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs.

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    Mian-Er Cong

    Full Text Available Pre-exposure prophylaxis (PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues.Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10. PrEP breakthrough infections continued treatment with 1-2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection.Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1-12 (p<0.005. SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043 but not throughout weeks 12-20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo.Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.

  14. Highly active antiretroviral therapy normalizes the function of progenitor cells in human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Dam Nielsen, S.; Ersbøll, A. K.; Mathiesen, L.

    1998-01-01

    -infected patients were determined prior to HAART and after 2, 4, 8, and 12 weeks of therapy. The mean number of colony-forming units (cells) per milliliter (cfu/mL) was 15.0 prior to HAART vs. 109.8 in healthy controls (P.../mL eliminated the differences between HIV-infected patients and controls. Significant increases in numbers of CD34 cells were not detected. Of importance, the cloning efficiency of CD34 cells increased from 1.7% prior to therapy to a peak at 18.7% (P=.003). In conclusion, HAART normalized CD34 cell function...

  15. Significant Depletion of CD4+ T Cells Occurs in the Oral Mucosa during Simian Immunodeficiency Virus Infection with the Infected CD4+ T Cell Reservoir Continuing to Persist in the Oral Mucosa during Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Jeffy George

    2015-01-01

    Full Text Available Human and simian immunodeficiency virus (HIV and SIV infections are characterized by manifestation of numerous opportunistic infections and inflammatory conditions in the oral mucosa. The loss of CD4+ T cells that play a critical role in maintaining mucosal immunity likely contributes to this process. Here we show that CD4+ T cells constitute a minor population of T cells in the oral mucosa and display a predominantly central memory phenotype mirroring other mucosal sites such as the rectal mucosa. Chronic SIV infection was associated with a near total depletion of CD4+ T cells in the oral mucosa that appear to repopulate during antiretroviral therapy (ART. Repopulating CD4+ T cells harbored a large fraction of Th17 cells suggesting that ART potentially reconstitutes oral mucosal immunity. However, a minor fraction of repopulating CD4+ T cells harbored SIV DNA suggesting that the viral reservoir continues to persist in the oral mucosa during ART. Therapeutic approaches aimed at obtaining sustainable CD4+ T cell repopulation in combination with strategies that can eradicate the latent viral reservoir in the oral mucosa are essential for better oral health and long-term outcome in HIV infected patients.

  16. Cutting edge: Rapid recovery of NKT cells upon institution of highly active antiretroviral therapy for HIV-1 infection

    NARCIS (Netherlands)

    van der Vliet, Hans J. J.; van Vonderen, Marit G. A.; Molling, Johan W.; Bontkes, Hetty J.; Reijm, Martine; Reiss, Peter; van Agtmael, Michiel A.; Danner, Sven A.; van den Eertwegh, Alfons J. M.; von Blomberg, B. Mary E.; Scheper, Rik J.

    2006-01-01

    CD1d-restricted NKT cells play important regulatory roles in various immune responses and are rapidly and selectively depleted upon infection with HIV-1. The cause of this selective depletion is incompletely understood, although it is in part due to the high susceptibility of CD4+ NKT cells to

  17. Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting

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    Lawn Stephen D

    2008-07-01

    Full Text Available Abstract Background Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. Methods In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART, VL measurements and risk of virological failure (VL > 1,000 copies/ml following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (ΔCD4 count and the difference between consecutive values (CD4 count slope using all 3-monthly CD4 count measurements during follow-up. Results During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179, VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003, ΔCD4 counts (r = - 0.11, P P P = 0.99, P = 0.92 and P = 0.75, respectively. Moreover, in a receiver operating characteristic (ROC curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%. Conclusion CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.

  18. Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G-CSF a candidate for use in gene therapy or to support antiretroviral therapy

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Dam-Larsen, S

    1998-01-01

    The potential of granulocyte colony-stimulating factor (G-CSF) to mobilize CD4 cells and/or CD34 cells for use in gene therapy or to support antiretroviral therapy was examined. Ten human immunodeficiency virus-infected patients were treated with G-CSF (300 microg/day) for 5 days. Numbers of CD4.......01/microL (P CSF induced increases in numbers of CD34 cells and CD4 cells in HIV-infected patients...

  19. Adipocytes Impair Efficacy of Antiretroviral Therapy

    Science.gov (United States)

    Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

    2018-01-01

    Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

  20. Effect of cytomegalovirus co-infection on normalization of selected T-cell subsets in children with perinatally acquired HIV infection treated with combination antiretroviral therapy.

    Science.gov (United States)

    Kapetanovic, Suad; Aaron, Lisa; Montepiedra, Grace; Anthony, Patricia; Thuvamontolrat, Kasalyn; Pahwa, Savita; Burchett, Sandra; Weinberg, Adriana; Kovacs, Andrea

    2015-01-01

    We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.

  1. Effect of cytomegalovirus co-infection on normalization of selected T-cell subsets in children with perinatally acquired HIV infection treated with combination antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Suad Kapetanovic

    Full Text Available We examined the effect of cytomegalovirus (CMV co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+ children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART-algorithm study.Participants were categorized as CMV-naïve, CMV-positive (CMV+ viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+, activated (CD38+HLA-DR+ and terminally differentiated (CD62L-CD45RA+; CD95+CD28- CD4+ and CD8+ T-cells were measured by flow cytometry.Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets.In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.

  2. Atypical manifestation of progressive outer retinal necrosis in AIDS patient with CD4+ T-cell counts more than 100 cells/microL on highly active antiretroviral therapy.

    Science.gov (United States)

    Vichitvejpaisal, Pornpattana; Reeponmahar, Somporn; Tantisiriwat, Woraphot

    2009-06-01

    Typical progressive outer retinal necrosis (PORN) is an acute ocular infectious disease in acquired immunodeficiency syndrome (AIDS) patients with extremely low CD4+ T-cell counts. It is a form of the Varicella- zoster virus (VZV) infection. This destructive infection has an extremely rapid course that may lead to blindness in affected eyes within days or weeks. Attempts at its treatment have had limited success. We describe the case of a bilateral PORN in an AIDS patient with an initial CD4+ T-cell count >100 cells/microL that developed after initiation of highly active antiretroviral therapy (HAART). A 29-year-old Thai female initially diagnosed with human immunodeficiency virus (HIV) in 1998, presented with bilaterally decreased visual acuity after initiating HAART two months earlier. Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis. Her CD4+ T-cell count was 127 cells/microL. She was diagnosed as having PORN based on clinical features and positive VZV in the aqueous humor and vitreous by polymerase chain reaction (PCR). Despite combined treatment with intravenous acyclovir and intravitreous ganciclovir, the patient's visual acuity worsened with no light-perception in either eye. This case suggests that PORN should be included in the differential diagnosis of reduced visual acuity in AIDS patients initiating HAART with higher CD4+ T-cell counts. PORN may be a manifestation of the immune reconstitution syndrome.

  3. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL

    DEFF Research Database (Denmark)

    O'Connor, Jemma; Vjecha, Michael J; Phillips, Andrew N

    2017-01-01

    BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high...... μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4...... had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26-0·57, p

  4. HIV-1–Infected Individuals in Antiretroviral Therapy React Specifically With Polyfunctional T-Cell Responses to Gag p24

    DEFF Research Database (Denmark)

    Brandt, Lea; Benfield, Thomas; Kronborg, Gitte

    2013-01-01

    Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine.......Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine....

  5. Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection

    Science.gov (United States)

    Ananworanich, Jintanat; Schuetz, Alexandra; Vandergeeten, Claire; Sereti, Irini; de Souza, Mark; Rerknimitr, Rungsun; Dewar, Robin; Marovich, Mary; van Griensven, Frits; Sekaly, Rafick; Pinyakorn, Suteeraporn; Phanuphak, Nittaya; Trichavaroj, Rapee; Rutvisuttinunt, Wiriya; Chomchey, Nitiya; Paris, Robert; Peel, Sheila; Valcour, Victor; Maldarelli, Frank; Chomont, Nicolas; Michael, Nelson; Phanuphak, Praphan; Kim, Jerome H.

    2012-01-01

    Background Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy. Methods and Findings We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm3. HIV RNA was 5.5 log10 copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/106 PBMC) vs. Fiebig I (8 copy/106 PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of HIV DNA at week 0 predicted reservoir size at week 24 (pHIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02). Conclusions Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission. PMID:22479485

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

    Science.gov (United States)

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

    2018-02-14

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

  7. Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura

    2008-01-01

    OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...

  8. Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

    Science.gov (United States)

    Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

    2014-06-01

    The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

  9. In-depth analysis of patient-clinician cell phone communication during the WelTel Kenya1 antiretroviral adherence trial.

    Directory of Open Access Journals (Sweden)

    Mia L van der Kop

    Full Text Available The WelTel Kenya1 trial demonstrated that text message support improved adherence to antiretroviral therapy (ART and suppression of HIV-1 RNA load. The intervention involved sending weekly messages to patients inquiring how they were doing; participants were required to respond either that they were well or that there was a problem.1 Describe problems participants identified through mobile phone support and reasons why participants did not respond to the messages; 2 investigate factors associated with indicating a problem and not responding; and 3 examine participant perceptions of the intervention.Secondary analysis of WelTel Kenya1 trial data.Reasons participants indicated a problem or did not respond were extracted from the study log. Negative binomial regression was used to determine participant characteristics associated with indicating a problem and non-response. Data from follow-up questionnaires were used to describe participant perceptions of the intervention.Between 2007 and 2009, 271 participants generated 11,873 responses; 377 of which indicated a problem. Health issues were the primary reason for problem responses (72%. Rural residence (adjusted incidence rate ratio [IRR] 1.96; 95%CI 1.19-3.25; p=0.009 and age were associated with indicating a problem (adjusted IRR 0.63 per increase in age group category; 95%CI 0.50-0.80; p<0.001. Higher educational level was associated with a decreased rate of non-response (adjusted IRR 0.81; 95%CI 0.69-0.94; p=0.005. Of participants interviewed, 62% (n=129 stated there were no barriers to the intervention; cell phone issues were the most common barrier. Benefits included reminding patients to take medication and promoting a feeling that "someone cares".The WelTel intervention enabled frequent communication between clinicians and patients during the WelTel Kenya1 trial. Many patients valued the service for the support it provided, with health-related concerns comprising the majority of problems

  10. Individualization of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Pavlos R

    2011-12-01

    Full Text Available Rebecca Pavlos, Elizabeth J PhillipsInstitute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, AustraliaAbstract: Antiretroviral therapy (ART has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual's environment that may be dynamic over time] information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care.Keywords: HIV

  11. Assessment of antiretroviral treatment outcome in public hospitals ...

    African Journals Online (AJOL)

    Bernt Lindtjørn

    2009-01-31

    Jan 31, 2009 ... CD4 cell count is less than 350 and all WHO stage IV and CD4 cell count ..... Katherine H, et al: Antiretroviral therapy and early mortality in South ... Evan W, Robert S, Benita Y, Richard H, Michael V. Julio SG. ... Kara W, Silvester K, Lameck D, Abraham S, John S,. Constantin T ... Janet G, et al. Predicators of ...

  12. Immunosenescence of the CD8(+) T cell compartment is associated with HIV-infection, but only weakly reflects age-related processes of adipose tissue, metabolism, and muscle in antiretroviral therapy-treated HIV-infected patients and controls

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Langkilde, Anne; Haupt, Thomas Huneck

    2015-01-01

    of immunosenescence is not well established. Studying immunosenescence in HIV-infection could give insight into its role in ageing processes. In this cross-sectional study, we aimed to investigate whether ART-treated HIV-infected patients exhibit immunosenescence; and whether immunosenescence is associated with age......BACKGROUND: Despite effective antiretroviral therapy (ART), HIV-infected patients exhibit systemic inflammation, early onset of age-related diseases, and features of immunosenescence. The role of inflammation in the development of age-related diseases is widely recognized. However, the role......-related processes of inflammation, metabolism, adipose tissue, and muscle. T cell immunosenescence and exhaustion were assessed by flow cytometry analysis of CD8 (+) cells from 43 ART-treated HIV-infected patients (HIV(+)) and ten Controls using markers of differentiation: CD27/CD28; maturation: CD27/CD45RA...

  13. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Neuhaus, Jacqueline; Babiker, Abdel G

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts a...

  14. Challenges in Initiating Antiretroviral Therapy in 2010

    Directory of Open Access Journals (Sweden)

    Cécile L Tremblay

    2010-01-01

    Full Text Available Many clinical trials have shown that initiating antiretroviral therapy (ART at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient’s preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.

  15. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    -naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

  16. CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa.

    Science.gov (United States)

    Geng, Elvin H; Neilands, Torsten B; Thièbaut, Rodolphe; Bwana, Mwebesa Bosco; Nash, Denis; Moore, Richard D; Wood, Robin; Zannou, Djimon Marcel; Althoff, Keri N; Lim, Poh Lian; Nachega, Jean B; Easterbrook, Philippa J; Kambugu, Andrew; Little, Francesca; Nakigozi, Gertrude; Nakanjako, Damalie; Kiggundu, Valerian; Ki Li, Patrick Chung; Bangsberg, David R; Fox, Matthew P; Prozesky, HansW; Hunt, Peter W; Davies, Mary-Ann; Reynolds, Steven J; Egger, Matthias; Yiannoutsos, Constantin T; Vittinghoff, Eric V; Deeks, Steven G; Martin, Jeffrey N

    2015-02-01

    Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517–541] in North America, 494/ml (95% CI: 429–559) in West Africa, 515/ml (95% CI: 508–522) in Southern Africa, 503/ml (95% CI: 478–528) in Asia and 437/ml (95% CI: 425–449) in East Africa. CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

  17. Trends in CD4 cell count response to first-line antiretroviral treatment in HIV-positive patients from Asia, 2003-2013: TREAT Asia HIV Observational Database Low Intensity Transfer.

    Science.gov (United States)

    De La Mata, Nicole L; Ly, Penh S; Ng, Oon T; Nguyen, Kinh V; Merati, Tuti P; Pham, Thuy T; Lee, Man P; Choi, Jun Y; Sohn, Annette H; Law, Matthew G; Kumarasamy, Nagalingeswaran

    2017-11-01

    Antiretroviral treatment (ART) guidelines have changed over the past decade, recommending earlier initiation and more tolerable regimens. The study objective was to examine the CD4 response to ART, depending on the year of ART initiation, in HIV-positive patients in the Asia-Pacific. We included HIV-positive adult patients who initiated ART between 2003 and 2013 in our regional cohort from eight urban referral centres in seven countries within Asia. We used mixed-effects linear regression models to evaluate differences in CD4 response by year of ART initiation during 36 months of follow-up, adjusted a priori for other covariates. Overall, 16,962 patients were included. Patients initiating in 2006-9 and 2010-13 had an estimated mean CD4 cell count increase of 8 and 15 cells/µl, respectively, at any given time during the 36-month follow-up, compared to those in 2003-5. The median CD4 cell count at ART initiation also increased from 96 cells/µl in 2003-5 to 173 cells/µl in 2010-13. Our results suggest that the CD4 response to ART is modestly higher for those initiating ART in more recent years. Moreover, fewer patients are presenting with lower absolute CD4 cell counts over time. This is likely to reduce their risk of opportunistic infections and future non-AIDS defining cancers.

  18. Perceptions of HIV infected patients on the use of cell phone as a tool to support their antiretroviral adherence; a cross-sectional study in a large referral hospital in Kenya.

    Science.gov (United States)

    Kinyua, Florence; Kiptoo, Michael; Kikuvi, Gideon; Mutai, Joseph; Meyers, Adrienne F A; Muiruri, Peter; Songok, Elijah

    2013-10-21

    Clinical trials were conducted to assess the feasibility of using a cell phone text messaging-based system to follow up Human Immunodeficiency Virus (HIV) infected patients on antiretroviral (ARTs) and assess for improved adherence to their medication. However there is need to evaluate the perceptions of the HIV infected patients towards the use of these cell phones in an effort to better aid in the clinical management of their HIV infection. The objective of this study was therefore to determine the perceptions of HIV infected patients on the use of cell phone text messaging as a tool to support adherence to their ART medication. A cross sectional survey was conducted among patients receiving Highly Active Anti-Retroviral Therapy (HAART) at the Kenyatta National Hospital Comprehensive Care Clinic in Nairobi between May and July, 2011. Pre-tested questionnaires were used to collect the socio-demographic and perceptions data. The recruitment of the participants was done using the random probability sampling method and statistical analysis of data performed using Statistical Package for Social Sciences (SPSS) version 16.0. A total of 500 HIV infected patients (Male-107, Female-307) aged 19-72 years were interviewed. The majority of individuals (99%) had access to cell phones and 99% of the HIV infected patients interviewed supported the idea of cell phone use in management of their HIV infection. A large proportion (46%) claimed that they needed cell phone access for medical advice and guidance on factors that hinder their adherence to medication and only 3% of them needed it as a reminder to take their drugs. The majority (72%) preferred calling the healthcare provider with their own phones for convenience and confidential purposes with only 0.4% preferring to be called or texted by the health care provider. Most (94%), especially the older patients, had no problem with their confidentiality being infringed in the process of the conversation as per the bivariate

  19. CD4+ T follicular helper and IgA+ B cell numbers in gut biopsies from HIV-infected subjects on antiretroviral therapy are comparable to HIV-uninfected individuals

    Directory of Open Access Journals (Sweden)

    John Zaunders

    2016-10-01

    Full Text Available Background: Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation and progression of HIV-1 infection. Antiretroviral therapy (ART may lead to reconstitution of CD4+ T cells in gastrointestinal-associated lymphoid tissue (GALT, but its impact on humoral immunity within GALT is unclear. Therefore we studied CD4+ subsets, including T follicular helper cells (Tfh, as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV+ subjects on suppressive ART, compared to HIV-negative controls.Methods: 23 HIV+ subjects on ART and 22 HIV-negative controls (HNC undergoing colonoscopy were recruited to the study. Single cell suspensions were prepared from biopsies from left colon (LC, right colon (RC and terminal ileum (TI. T and B lymphocyte subsets, as well as EpCAM+ epithelial cells, were accurately enumerated by flow cytometry, using counting beads. Results: No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4+ T cell count/106 epithelial cells was 2.4-fold lower in HIV+ subjects versus HNC (19,679 vs 47,504 cells; p=0.02. Similarly, median LC CD4+ T cell counts were reduced in HIV+ subjects (8,358 vs 18,577; p=0.03, but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA+ B cell counts at either site between HIV+ subjects and HNC. Further analysis showed no difference in CD4+, Tfh or IgA+ B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4+ T cells, including: CCR5+ cells; CD127+ long-term memory cells; CD103+ tissue resident cells; or CD161+ cells (surrogate marker for Th17, but there was a slight increase in the proportion of T regulatory cells. Conclusion: While there

  20. 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.

  1. Initiation of antiretroviral therapy in patients with a CD4 count of less than 350 cells: a retrospective audit against key indicators from the CQUIN payment framework.

    Science.gov (United States)

    Mercer, R M; Olarinde, O; Ryan, C; Greig, J; Yeeles, H; Walker, A; Walker, H; Meardon, N C

    2011-12-01

    A proportion of funding for the South Yorkshire HIV Network is dependant on meeting the targets of the Commissioning for Quality and Innovation (CQUIN) payment framework. This states that 85% of patients with a CD4 count below 350 should be on antiretroviral therapy (ART). We also audited how many patients we started on treatment within six weeks. We found 88% of the 243 patients were on ART at the end of the audit, but significantly less had been started on treatment within six weeks of their CD4 count falling below 350. Although the target was achieved, there were patients who should be excluded as shown by other clinical guidelines, for example patients on treatment for tuberculosis. If these patients were excluded and the threshold level increased, it would help emphasize the at-risk patient group and lead to a fairer allocation of funding.

  2. Antiretroviral activity of protease inhibitors against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Lianet Monzote

    2013-02-01

    Full Text Available The introduction of highly active antiretroviral therapy (HAART has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE. These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.

  3. Efficacy and Safety of Antiretroviral Therapy Initiated One Week after Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/μL: TB-HAART Study, a Randomized Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Wondwossen Amogne

    Full Text Available Given the high death rate the first two months of tuberculosis (TB therapy in HIV patients, it is critical defining the optimal time to initiate combination antiretroviral therapy (cART.A randomized, open-label, clinical trial comparing efficacy and safety of efavirenz-based cART initiated one week, four weeks, and eight weeks after TB therapy in patients with baseline CD4 count < 200 cells/μL was conducted. The primary endpoint was all-cause mortality rate at 48 weeks. The secondary endpoints were hepatotoxicity-requiring interruption of TB therapy, TB-associated immune reconstitution inflammatory syndrome, new AIDS defining illnesses, CD4 counts, HIV RNA levels, and AFB smear conversion rates. All analyses were intention-to-treat.We studied 478 patients with median CD4 count of 73 cells/μL and 5.2 logs HIV RNA randomized to week one (n = 163, week four (n = 160, and week eight (n = 155. Sixty-four deaths (13.4% occurred in 339.2 person-years. All-cause mortality rates at 48 weeks were 25 per 100 person-years in week one, 18 per 100 person-years in week four and 15 per 100 person-years in week eight (P = 0.2 by the log-rank test. All-cause mortality incidence rate ratios in subgroups with CD4 count below 50 cells/μL versus above were 2.8 in week one (95% CI 1.2-6.7, 3.1 in week four (95% CI 1.2-8.6 and 5.1 in week eight (95% CI 1.8-16. Serum albumin < 3 gms/dL (adjusted HR, aHR = 2.3 and CD4 < 50 cells/μL (aHR = 2.7 were independent predictors of mortality. Compared with similar subgroups from weeks four and eight, first-line TB treatment interruption was high in week one deaths (P = 0.03 and in the CD4 subgroup <50 cells/μL (P = 0.02.Antiretroviral therapy one week after TB therapy doesn't improve overall survival. Despite increased mortality with CD4 < 50 cells/μL, we recommend cART later than the first week of TB therapy to avoid serious hepatotoxicity and treatment interruption.ClinicalTrials.gov NCT 01315301.

  4. Influence of highly active antiretroviral therapy (HAART) on the ...

    African Journals Online (AJOL)

    This report is part of the ongoing highly active antiretroviral therapy (HAART) trial, 167 patients were enlisted, but current analysis was restricted to 107 patients that were about a year old on the programme. The baseline weight, CD4+ cell count and serum albumin of 59 males and 48 females age 15-60 years, were ...

  5. Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

    NARCIS (Netherlands)

    Heine, R. ter

    2009-01-01

    The aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment.

  6. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

    Directory of Open Access Journals (Sweden)

    Jim Young

    Full Text Available Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

  7. Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Graeme Meintjes

    2015-12-01

    Full Text Available The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults. The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

  8. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

    OpenAIRE

    Montoya Carlos J; Jaimes Fabian; Higuita Edwin A; Convers-Páez Sandra; Estrada Santiago; Gutierrez Francisco; Amariles Pedro; Giraldo Newar; Peñaloza Cristina; Rugeles Maria T

    2009-01-01

    Abstract Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregul...

  9. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage

    DEFF Research Database (Denmark)

    Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John

    2014-01-01

    therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. METHODS: We used several independent mathematical models in four settings-South Africa (generalised...... epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits......, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μ...

  10. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred

    2015-01-01

    BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV...... entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients...... in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells...

  11. 2B4 expression on natural killer cells increases in HIV-1 infected patients followed prospectively during highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Ostrowski, S R; Ullum, H; Pedersen, Bente Klarlund

    2005-01-01

    Human immunodeficiency virus (HIV)-1 infection influences natural killer (NK) cell expression of inhibitory NK receptors and activating natural cytotoxicity receptors. It is unknown whether expression of the co-stimulatory NK cell receptor 2B4 (CD244) on NK cells and CD3+ CD8+ cells are affected ...

  12. Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Tânia R.C. Vergara

    2017-09-01

    Conclusions: Short-term use of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4+ cell count without changes to the CD8+ cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication.

  13. Renal impairment in a rural African antiretroviral programme

    Directory of Open Access Journals (Sweden)

    Lessells Richard J

    2009-08-01

    Full Text Available Abstract Background There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods (i Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR of significantly impaired renal function (combining severe and moderate impairment. Co-variates for analysis were age, sex and CD4 count at initiation. Results (i There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8 whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5 with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl. In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1, male gender (aOR 1.89, 95% C.I. 1.39–2.56 and CD4 Conclusion In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited.

  14. Low-Dose Growth Hormone for 40 Weeks Induces HIV-1-Specific T-Cell Responses in Patients on Effective Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Herasimtschuk, Anna A; Hansen, Birgitte R; Langkilde, Anne

    2013-01-01

    changes. Subjects with the most robust responses in the ELISpot assays had improved thymic function following rhGH administration, as determined using CD4(+) T-cell receptor rearrangement excision circle (TREC) and thymic density data from the original study. T cells from these robust responders were...

  15. 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....

  16. Antiretroviral Tissue Kinetics: In Vivo Imaging Using Positron Emission Tomography▿

    OpenAIRE

    Di Mascio, Michele; Srinivasula, Sharat; Bhattacharjee, Abesh; Cheng, Lily; Martiniova, Lucia; Herscovitch, Peter; Lertora, Juan; Kiesewetter, Dale

    2009-01-01

    Our current knowledge on the antiviral efficacy, dosing, and toxicity of available highly active antiretroviral therapy regimens is mostly derived from plasma or blood kinetics of anti-human immunodeficiency virus (anti-HIV) drugs. However, the blood comprises only 2% of the total target cells in the body. Tissue drug levels may differ substantially from corresponding plasma levels, and drug distribution processes may be characterized by high intertissue variability, leading to suboptimal tar...

  17. Combined antiretroviral and anti- tuberculosis drug resistance ...

    African Journals Online (AJOL)

    these epidemics, many challenges remain.[3] Antiretroviral and anti-TB drug resistance pose considerable threats to the control of these epidemics.[4,5]. The breakdown in HIV/TB control within prisons is another emerging threat.[6,7] We describe one of the first reports of combined antiretroviral and anti-TB drug resistance ...

  18. Preliminary investigation of adherence to antiretroviral therapy ...

    African Journals Online (AJOL)

    Treatment of HIV with highly active antiretroviral therapy (HAART) has resulted in declining morbidity and mortality rates from HIV-associated diseases, but concerns regarding access and adherence are growing. To determine the adherence level and the reasons for non-adhering to antiretroviral therapy (ART) among ...

  19. NEW DRUGS NEW TARGETS AND NOVEL ANTIRETROVIRALS

    African Journals Online (AJOL)

    2005-11-02

    Nov 2, 2005 ... Highly active antiretroviral therapy (HAART) has to date been based on use of a triple combination of drugs chosen from three classes of antiretrovirals (ARVs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).

  20. During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

    Directory of Open Access Journals (Sweden)

    Alessandra Ruggiero

    2015-09-01

    Conclusions: The observed positive association between integrated HIV-1 DNA load and frequency of CD8+DR/DP/DQ+ cells indicates that a close correlation between HIV persistence and immune activation continues during consistently suppressive therapy. The inducers of the distinct activation profile warrant further investigation.

  1. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

    DEFF Research Database (Denmark)

    Ledergerber, Bruno; Lundgren, Jens D; Walker, A Sarah

    2014-01-01

    Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure....

  2. Trends in baseline CD4 cell counts and risk factors for late antiretroviral therapy initiation among HIV-positive patients in Shanghai, a retrospective cross-sectional study.

    Science.gov (United States)

    Sun, Jianjun; Liu, Li; Shen, Jiayin; Chen, Panpan; Lu, Hongzhou

    2017-04-19

    There are few studies focus on the factors underlying the late initiation of ART in China. We analyzed the trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART in Shanghai, China. A retrospective cross-sectional survey was made in the Department of Infectious Disease of Shanghai Public Health Clinical Center which is a designated diagnosis and treatment center for HIV-positive patients in Shanghai during the period of January 1st, 2008--June 30th, 2014. Late ART initiation was defined as a CD4 cell count 30 years) (p HIV exposure who are male, older even heterosexual orientation should be given more opportunities to receive frequently screening, earlier diagnoses and timely treatment.

  3. Antiretroviral therapy increases thymic output in children with HIV

    DEFF Research Database (Denmark)

    Schou Sandgaard, Katrine; Lewis, Joanna; Adams, Stuart

    2014-01-01

    OBJECTIVE: Disease progression and response to antiretroviral therapy (ART) in HIV-infected children is different to that of adults. Immune reconstitution in adults is mainly from memory T cells, whereas in children it occurs predominantly from the naive T-cell pool. It is unclear however what...... with a recently described mathematical model to give explicit measures of thymic output. RESULTS: We found that age-adjusted thymic output is reduced in untreated children with HIV, which increases significantly with length of time on ART. CONCLUSION: Our results suggest that a highly active thymus in early...

  4. Examining the production costs of antiretroviral drugs.

    Science.gov (United States)

    Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

    2006-08-22

    To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

  5. Opportunistic disease and mortality in patients coinfected with hepatitis B or C virus in the strategic management of antiretroviral therapy (SMART) study

    DEFF Research Database (Denmark)

    Tedaldi, Ellen; Peters, Lars; Neuhaus, Jacquie

    2008-01-01

    BACKGROUND: In the Strategic Management of Antiretroviral Therapy (SMART) study, the risk of opportunistic disease (OD) and/or death due to any cause was elevated in the drug conservation (i.e., interrupt antiretroviral therapy until the CD4(+) cell count is

  6. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

    NARCIS (Netherlands)

    Eaton, J.W.; Menzies, N.A.; Stover, J.; Cambiano, V.; Chindelevitch, L.; Cori, A.; Hontelez, J.A.; Humair, S.; Kerr, C.C.; Klein, D.J.; Mishra, S.; Mitchell, K.M.; Nichols, B.E.; Vickerman, P.; Bakker, R; Barnighausen, T.; Bershteyn, A.; Bloom, D.E.; Boily, M.C.; Chang, S.T.; Cohen, T.; Dodd, P.J.; Fraser, C.; Gopalappa, C.; Lundgren, J.; Martin, N.K.; Mikkelsen, E.; Mountain, E.; Pham, Q.D.; Pickles, M.; Phillips, A.; Platt, L.; Pretorius, C.; Prudden, H.J.; Salomon, J.A.; Vijver, D.A. van de; Vlas, S.J. de; Wagner, B.G.; White, R.G.; Wilson, D.P.; Zhang, L.; Blandford, J.; Meyer-Rath, G.; Remme, M.; Revill, P.; Sangrujee, N.; Terris-Prestholt, F.; Doherty, M.; Shaffer, N.; Easterbrook, P.J.; Hirnschall, G.; Hallett, T.B.

    2014-01-01

    BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per muL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral

  7. [Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription].

    Science.gov (United States)

    Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M

    2017-08-01

    In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m 2  and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to

  8. ORIGINAL ARTICLES Antiretroviral treatment for children

    African Journals Online (AJOL)

    Kaplan-Meier survival estimate for 407 children at 1 year was. 84% (95% ... highly active antiretroviral therapy (HAART) to 3 million people living with HIV I AIDS in ... 5 Furthermore, improvements in growth and body composition parameters,.

  9. ORIGINAL ARTICLES Estimation of adult antiretroviral treatment ...

    African Journals Online (AJOL)

    workplace treatment programmes (WPTPs) and NGO ..... Our analysis also demonstrates significant inequality .... paying for their own treatment outside of DMPs,15 which may ... of antiretroviral coverage in men and women and to develop.

  10. Monitoring of HIV viral load, CD4 cell count, and clinical assessment versus clinical monitoring alone for antiretroviral therapy in low-resource settings (Stratall ANRS 12110/ESTHER) : a cost-effectiveness analysis

    OpenAIRE

    Boyer, S.; March, L.; Kouanfack, C.; Laborde-Balen, G.; Marino, P.; Aghokeng Fobang, Avelin; Mpoudi-Ngole, E.; Koulla-Shiro, S.; Delaporte, Eric; Carrieri, M. P.; Spire, B.; Laurent, Christian; Moatti, Jean-Paul

    2013-01-01

    Background In low-income countries, the use of laboratory monitoring of patients taking antiretroviral therapy (ART) remains controversial in view of persistent resource constraints. The Stratall trial did not show that clinical monitoring alone was non-inferior to laboratory and clinical monitoring in terms of immunological recovery. We aimed to evaluate the costs and cost-effectiveness of the ART monitoring approaches assessed in the Stratall trial. Methods The randomised, controlled, non-i...

  11. Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial

    DEFF Research Database (Denmark)

    Baker, Jason V; Sharma, Shweta; Achhra, Amit C

    2017-01-01

    INTRODUCTION: HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. METHODS AND RESULTS: We studied cardiovascular disease risk factor changes in the START...... (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4+ cell counts >500 cells/mm3. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups....... The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm3, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg...

  12. Improving adherence to antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Nischal K

    2005-01-01

    Full Text Available Antiretroviral therapy (ART has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen′s pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression, lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.

  13. Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

    Science.gov (United States)

    Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M; Bryson, Yvonne; Culnane, Mary; Hughes, Michael D; O'Sullivan, M J; Scott, Gwendolyn; Stek, Alice M; Wara, Diane; Bulterys, Marc

    2002-06-13

    Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants. The association between combination therapy with protease inhibitors and an increased risk of very low birth weight requires confirmation.

  14. Reasons for not starting antiretroviral therapy in HIV-1-infected individuals : a changing landscape

    NARCIS (Netherlands)

    Fehr, Jan; Nicca, Dunja; Goffard, Jean Christophe; Haerry, David; Schlag, Michael; Papastamopoulos, Vasileios; Hoepelman, Andy; Skoutelis, Athanasius; Diazaraque, Ruth; Ledergerber, Bruno

    Purpose A cross-sectional survey was conducted to better understand why chronically HIV-1-infected individuals stratified by CD4 count (≤349; 350–499; ≥500 cells/μL) were not on antiretroviral therapy (ART). Methods Before the consultation, treatment-naive patients and their physicians independently

  15. Interruption of antiretroviral therapy is associated with increased plasma cystatin C

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Wyatt, Christina; Szczech, Lynda

    2009-01-01

    BACKGROUND: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to contin...

  16. Immunological Analysis of Treatment Interruption After Early Highly Active Antiretroviral Therapy

    NARCIS (Netherlands)

    Schellens, Ingrid M. M.; Pogany, Katalin; Westerlaken, Geertje H. A.; Borghans, José A. M.; Miedema, Frank; van Valkengoed, Irene G. M.; Kroon, Frank P.; Lange, Joep M. A.; Brinkman, Kees; Prins, Jan M.; van Baarle, Debbie

    2010-01-01

    We longitudinally evaluated HIV-specific T-cell immunity after discontinuation of highly active antiretroviral therapy (HAART). After treatment interruption (TI), some individuals could maintain a low plasma viral load ( <15,000 copies/mL), whereas others could not (>50,000 copies/mL). Before HAART

  17. Platelet count kinetics following interruption of antiretroviral treatment

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V

    2013-01-01

    To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow...

  18. The association between HIV, antiretroviral therapy, and gestational diabetes mellitus

    NARCIS (Netherlands)

    Soepnel, Larske M; Norris, Shane A; Schrier, Verena J M M; Browne, Joyce L; Rijken, Marcus J; Gray, Glenda; Klipstein-Grobusch, Kerstin

    2017-01-01

    OBJECTIVES: The widespread, chronic use of antiretroviral therapy raises questions concerning the metabolic consequences of HIV infection and treatment. Antiretroviral therapy, and specifically protease inhibitors, has been associated with hyperglycemia. As pregnant women are vulnerable to

  19. Antiretroviral therapy programme on control of HIV transmission in ...

    African Journals Online (AJOL)

    Antiretroviral therapy programme on control of HIV transmission in Morogoro municipality, Tanzania: A challenge for development. ... The government and partners should improve access to ART services to enable many PLHIV to access the services. Key words: Antiretroviral Therapy, Highly Active Antiretroviral Treatment, ...

  20. Antiretroviral therapy programme outcomes in Tshwane district ...

    African Journals Online (AJOL)

    Objectives. To ascertain patient retention on ART after 5 years on treatment in one district of Gauteng Province, SA, establish the number of patients ... A retrospective cohort study of patients initiated on highly active antiretroviral therapy (HAART) between January and March .... ferred-out patients from the total of 381 leaves.

  1. The discovery and development of antiretroviral agents

    NARCIS (Netherlands)

    Lange, Joep M. A.; Ananworanich, Jintanat

    2014-01-01

    Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral

  2. Perceived stigma and highly active antiretroviral treatment ...

    African Journals Online (AJOL)

    Perceived stigma and highly active antiretroviral treatment adherence among persons living with HIV/AIDS in the University of Port Harcourt Teaching Hospital. ... Data on socio-demographic characteristics, stigma and adherence to drug regimen were collected using a validated self-administered questionnaire. Data were ...

  3. Dual antiretroviral therapy for HIV infection.

    Science.gov (United States)

    Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo

    2017-08-01

    For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.

  4. Insulin resistance induced by antiretroviral drugs: Current ...

    African Journals Online (AJOL)

    Treatment with highly active antiretroviral therapy (HAART) has improved the prognosis of patients with AIDS, but it has also increased the incidence of various metabolic disorders, in particular insulin resistance accompanied by dyslipidaemia, hyperglycaemia and lipodystrophy. This is often accompanied by frank type 2 ...

  5. CROI 2016: Advances in Antiretroviral Therapy.

    Science.gov (United States)

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa.

  6. North-South Corridor Demonstration Project: Ethical and Logistical Challenges in the Design of a Demonstration Study of Early Antiretroviral Treatment for Long Distance Truck Drivers along a Transport Corridor through South Africa, Zimbabwe, and Zambia

    NARCIS (Netherlands)

    Gomez, G. B.; Venter, W. D. F.; Lange, J. M. A.; Rees, H.; Hankins, C.

    2013-01-01

    Background. Long-distance truck drivers are at risk of acquiring and transmitting HIV and have suboptimal access to care. New HIV prevention strategies using antiretroviral drugs to reduce transmission risk (early antiretroviral therapy (ART) at CD4 count >350 cells/ μ L) have shown efficacy in

  7. Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

    Science.gov (United States)

    das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2012-06-01

    To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

  8. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study

    NARCIS (Netherlands)

    Cain, Lauren E.; Logan, Roger; Robins, James M.; Sterne, Jonathan A. C.; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; van Sighem, Ard; de Wolf, Frank; Bucher, Heiner C.; von Wyl, Viktor; Esteve, Anna; Casabona, Jordi; del Amo, Julia; Moreno, Santiago; Seng, Remonie; Meyer, Laurence; Perez-Hoyos, Santiago; Muga, Roberto; Lodi, Sara; Lanoy, Emilie; Costagliola, Dominique; Hernan, Miguel A.; Ainsworth, J.; Anderson, J.; Babiker, A.; Delpech, V.; Dunn, D.; Easterbrook, P.; Fisher, M.; Gazzard, B.; Gilson, R.; Gompels, M.; Hill, T.; Johnson, M.; Leen, C.; Orkin, C.; Phillips, A.; Pillay, D.; Porter, K.; Sabin, C.; Schwenk, A.; Walsh, J.; Bansi, L.; Glabay, A.; Thomas, R.; Jones, K.; Perry, N.; Pullin, A.; Churchill, D.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Munshi, S.; Post, F.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Man, S. L.; Williams, I.; Dooley, D.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Wilson, A.; Bezemer, D. O.; Gras, L. A. J.; Kesselring, A. M.; van Sighem, A. I.; Smit, C.; Zhang, S.; Zaheri, S.; Prins, J. M.; Boer, K.; Bos, J. C.; Geerlings, S. E.; Godfried, M. H.; Haverkort, M. E.; Kuijpers, T. W.; Lange, J. M. A.; van der Meer, J. T. M.; Nellen, F. J. B.; Pajkrt, D.; van der Poll, T.; Reiss, P.; Scherpbier, H. J.; van der Valk, M.; Vrouenraets, S. M. E.; van Vugt, M.; Wit, F. W. M. N.; Schreij, G.; Lowe, S.; Oude Lashof, A.; Bravenboer, B.; Pronk, M. J. H.; van der Ende, M. E.; van der Feltz, M.; Gelinck, L. B. S.; Nouwen, J. L.; Rijnders, B. J. A.; de Ruiter, E. D.; Slobbe, L.; Schurink, C. A. M.; Verbon, A.; de Vries-Sluijs, T. E. M. S.; Driessen, G.; Hartwig, N. G.; Branger, J.; Kauffmann, R. H.; Schippers, E. F.; Groeneveld, P. H. P.; Alleman, M. A.; Bouwhuis, J. W.; ten Kate, R. W.; Soetekouw, R.; Kroon, F. P.; Arend, S. M.; de Boer, M. G. J.; van den Broek, P. J.; van Dissel, J. T.; Jolink, H.; van Nieuwkoop, C.; den Hollander, J. G.; Pogany, K.; Bronsveld, W.; Kortmann, W.; van Twillert, G.; Vriesendorp, R.; Leyten, E. M. S.; van Houte, D.; Polee, M. B.; van Vonderen, M. G. A.; ten Napel, C. H. H.; Kootstra, G. J.; Brinkman, K.; van den Berk, G. E. L.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van Eeden, A.; Verhagen, D. W. M.; Mulder, J. W.; van Gorp, E. C. M.; Smit, P. M.; Weijer, S.; Juttmann, J. R.; Brouwer, A. E.; van Kasteren, M. E. E.; Veenstra, J.; Lettinga, K. D.; Koopmans, P. P.; Brouwer, A. M.; Dofferhoff, A. S. M.; van der Flier, M.; de Groot, R.; ter Hofstede, H. J. M.; Keuter, M.; van der Ven, A. J. A. M.; Sprenger, H. G.; van Assen, S.; Doedens, R.; Scholvinck, E. H.; Stek, C. J.; Hoepelman, A. I. M.; Arends, J. E.; Ellerbroek, P. M.; van der Hilst, J. C. H.; Jaspers, C. A. J. J.; Maarschalk-Ellerbroek, L. J.; Oosterheert, J. J.; Peters, E. J. G.; Mudrikova, T.; Schneider, M. M. E.; Wassenberg, M. W. M.; Geelen, S. P. M.; Wolfs, T. F. W.; Danner, S. A.; van Agtmael, M. A.; Bierman, W. F. W.; Claessen, F. A. P.; de Jong, E. V.; Perenboom, R. M.; bij de Vaate, E. A.; Richter, C.; van der Berg, J.; Gisolf, E. H.; van den Berge, M.; Stegeman, A.; Duits, A. J.; Winkel, K.; Abgrall, S.; Barin, F.; Bentata, M.; Billaud, E.; Boue, F.; Burty, C.; Cabie, A.; Costagliola, D.; Cotte, L.; de Truchis, P.; Duval, X.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Gaud, C.; Gilquin, J.; Grabar, S.; Katlama, C.; Khuong, M. A.; Lang, J. M.; Lascaux, A. S.; Launay, O.; Mahamat, A.; Mary-Krause, M.; Matheron, S.; Meynard, J. L.; Pavie, J.; Pialoux, G.; Pilorge, F.; Poizot-Martin, I.; Pradier, C.; Reynes, J.; Rouveix, E.; Simon, A.; Tattevin, P.; Tissot-Dupont, H.; Viard, J. P.; Viget, N.; Salomon, V.; Jacquemet, N.; Guiguet, M.; Lanoy, E.; Lievre, L.; Selinger-Leneman, H.; Lacombe, J. M.; Potard, V.; Bricaire, F.; Herson, S.; Desplanque, N.; Girard, P. M.; Meyohas, M. C.; Picard, O.; Cadranel, J.; Mayaud, C.; Clauvel, J. P.; Decazes, J. M.; Gerard, L.; Molina, J. M.; Diemer, M.; Sellier, P.; Honore, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J. L.; Picard-Dahan, C.; Yeni, P.; Berthe, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Roudiere, L.; Fior, R.; Delfraissy, J. F.; Goujard, C.; Jung, C.; Lesprit, P.; Vittecoq, D.; Fraisse, P.; Rey, D.; Beck-Wirth, G.; Stahl, J. P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maiotre, M. F.; Hoen, B.; Eglinger, P.; Faller, J. P.; Borsa-Lebas, F.; Caron, F.; Daures, J. P.; May, T.; Rabaud, C.; Berger, J. L.; Remy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M. F.; Pontonnier, G.; Yasdanpanah, Y.; Dellamonica, P.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Delmont, J. P.; Moreau, J.; Gastaut, J. A.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J. M.; Allegre, T.; Blanc, P. A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J. P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J. M.; Touraine, J. L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Contant, M.; Aebi, C.; Battegay, M.; Bernasconi, E.; Boni, J.; Brazzola, P.; Bucher, H. C.; Burgisser, P.; Calmy, A.; Cattacin, S.; Cavassini, M.; Cheseaux, J. J.; Drack, G.; Dubs, R.; Egger, M.; Elzi, L.; Fischer, M.; Flepp, M.; Fontana, A.; Francioli, P.; Furrer, H. J.; Fux, C.; Gayet-Ageron, A.; Gerber, S.; Gorgievski, M.; Gunthard, H.; Gyr, T.; Hirsch, H.; Hirschel, B.; Hosli, I.; Husler, M.; Kaiser, L.; Kahlert, C.; Karrer, U.; Kind, C.; Klimkait, T.; Ledergerber, B.; Martinetti, G.; Martinez, B.; Muller, N.; Nadal, D.; Paccaud, F.; Pantaleo, G.; Raio, L.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schupbach, J.; Speck, R.; Taffe, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Wyler, C. A.; Yerly, S.; Casabona, J.; Miro, J. M.; Alquezar, A.; Isern, V.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J. M.; Aguero, F.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaro, J.; Masabeu, A.; Garcia, I.; Guadarrama, M.; Romero, A.; Agusti, C.; Montoliu, A.; Ortega, N.; Lazzari, E.; Puchol, E.; Sanchez, M.; Blanco, J. L.; Garcia-Alcaide, F.; Martinez, E.; Mallolas, J.; Lopez-Dieguez, M.; Garcia-Goez, J. F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M. C.; Olmo, M.; Barragan, P.; Saumoy, M.; Bolao, F.; Cabellos, C.; Pena, C.; Sala, M.; Cervantes, M.; Jose Amengual, M.; Navarro, M.; Penelo, E.; Barrufet, P.; Berenguer, J.; del Amo, J.; Garcia, F.; Gutierrez, F.; Labarga, P.; Moreno, S.; Munoz, M. A.; Caro-Murillo, A. M.; Sobrino, P.; Jarrin, I.; Gomez Sirvent, J. L.; Rodriguez, P.; Aleman, M. R.; Alonso, M. M.; Lopez, A. M.; Hernandez, M. I.; Soriano, V.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M. E.; Martin, L.; Ramirez, G.; de Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervas, R. L.; Iribarren, J. A.; Arrizabalaga, J.; Aramburu, M. J.; Camino, X.; Rodriguez-Arrondo, F.; von Wichmann, M. A.; Pascual, L.; Goenaga, M. A.; Masia, M.; Ramos, J. M.; Padilla, S.; Sanchez-Hellin, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Lopez, J. C.; Miralles, P.; Cosin, J.; Gutierrez, I.; Ramirez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Vilades, C.; Lopez-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J. L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuellar, S.; de los Santos, I.; Sanz, J.; Oteo, J. A.; Blanco, J. R.; Ibarra, V.; Metola, L.; Sanz, M.; Perez-Martinez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M. J.; Irigoyen, C.; Antela, A.; Casado, J. L.; Dronda, F.; Moreno, A.; Perez, M. J.; Lopez, D.; Gutierrez, C.; Hernandez, B.; Pumares, M.; Marti, P.; Garcia, L.; Page, C.; Hernandez, J.; Pena, A.; Munoz, L.; Parra, J.; Viciana, P.; Leal, M.; Lopez-Cortes, L. F.; Trastoy, M.; Mata, R.; Justice, A. C.; Fiellin, D. A.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J. L.; Hernan, M. A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J. M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Rimland, D.; Jones-Taylor, C.; Oursler, K. A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Brettle, R.; Darbyshire, J.; Fidler, S.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Cursley, A.; Ewings, F.; Fairbrother, K.; Gnatiuc, L.; Lodi, S.; Murphy, B.; Smit, E.; Ward, F.; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S. P. R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, A. J.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Goorney, B.; Howard, L.; Tayal, S.; Short, L.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, D. N.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; DeSouza, C. B.; Isaksen, A.; McDonald, L.; Franca, A.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P. J.; Mazhude, C.; Johnstone, R.; Fakoya, A.; Mchale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Rice, P.; Mullaney, S. A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Haynes, J.; Evans, E.; Ong, E.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M. R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A. M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, S. V.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Luzzi, G.; Fairley, I.; Wallis, F.; Loze, B.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Morel, P.; Timsit, J.; Oksenhendeler, E.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Ghosn, J.; Rannou, M. T.; Bergmann, J. F.; Badsi, E.; Rami, A.; Parrinello, M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Cabane, J.; Tredup, J.; Herriot, E.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A. P.; Baillat, V.; Lemoing, V.; Merle de Boever, C.; Tramoni, C.; Sobesky, G.; Abel, S.; Beaujolais, V.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Fournier, I.; Gerbe, J.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Souala, F.; Ratajczak, M.; Montpied, G.; Beytoux, J.; Jacomet, C.; Pare, A.; Morelon, S.; Olivier, C.; Lortholary, O.; Dupont, B.; Maignan, A.; Ragnaud, J. M.; Raymond, I.; Mondor, H.; Sobel, A.; Levy, Y.; Lelievre, J. D.; Dominguez, S.; Dumont, C.; Aumaitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M. C.; Muller, E.; Drenou, B.; Beck, C.; Benomar, M.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Amirat, N.; Brancion, C.; Touam, F.; Drobacheff, C.; Folzer, A.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J. M.; Fialaire, P.; Loison, J.; Galanaud, P.; Bornarel, D.; Six, M.; Ferret, P.; Batisse, D.; Gonzales-Canali, G.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Nau, P.; Bastides, F.; Boyer, L.; Wassoumbou, S.; Bernard, L.; Domart, Y.; Merrien, D.; Mignot, A.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Mourier, L.; Vinceneux, P.; Simonpoli, A. M.; Zeng, A.; Jacquet, M.; Fournier, L.; Fuzibet, J. G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Chaillou, S.; Sabah, M.; Pasteur, L.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; de Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Drogoul, M. P.; Poizot Martin, I.; Fabre, G.; Lambert de Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Veil, S.; Roche-Sicot, J.; Saraux, J. L.; Lepretre, A.; Fampin, B.; Uludag, A.; Morin, A. S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J. J.; Quinsat, D. T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Nicolle, C.; Debab, Y.; Tremollieres, F.; Perronne, V.; Duffaut, H.; Slama, B.; Perre, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Ballanger, R.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Beguinot, I.; Chambrin, V.; Pignon, C.; Estocq, G. A.; Levy, A.; Duracinsky, M.; Le Bras, P.; Ngussan, M. S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Piketty, C.; Karmochkine, M.; Eliaszewitch, M.; Jayle, D.; Kazatchkine, M.; Colasante, U.; Nouaouia, W.; Vilde, J. L.; Bollens, D.; Binet, D.; Diallo, B.; Fonquernie, L.; Lagneau, J. L.; Pietrie, M. P.; Sicard, D.; Stieltjes, N.; Michot, J.; Bourdillon, F.; Obenga, G.; Escaut, L.; Bolliot, C.; Schneider, L.; Iguertsira, M.; Tomei, C.

    2011-01-01

    Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. To identify the optimal CD4 cell

  9. Antiretroviral Resistance in HIV/AIDS Patients

    Science.gov (United States)

    Manosuthi, W.; MD

    2018-03-01

    The higher prevalence of HIV drug resistance was observed in areas with greater ART coverage. The HIV resistance-associated mutations occur when people have inadequate levels of antiretroviral drugs as well as inadequate potency, inadequate adherence, and preexisting resistance. The degree to drug cross-resistance is observed depends on the specific mutations and number of mutation accumulation. In the Southeast Asia region, the challenging of people with treatment failure is the availability and accessibility to subsequent new antiretroviral drugs to construct he second and salvage regimen. Genotypic resistance testing is a useful tool because it can identify the existing drug resistance-associated mutations under the selective drug pressure. Thus, understanding the basic interpretation of HIV drug resistance- associated mutation is useful in guiding clinical decisions for treatment-experienced people living with HIV.

  10. Guidelines for antiretroviral therapy in adults

    Directory of Open Access Journals (Sweden)

    G Meintjes

    2012-08-01

    Full Text Available These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in January 2008. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART in Southern Africa has continued to grow. Cohort studies from the region show excellent clinical outcomes; however, ART is still being started late (in advanced disease, resulting in relatively high early mortality rates. New data on antiretroviral (ARV tolerability in the region and several new ARV drugs have become available. Although currently few in number, some patients in the region are failing protease inhibitor (PI-based second-line regimens. To address this, guidelines on third-line (or ‘salvage’ therapy have been expanded.

  11. Complications of HIV Disease and Antiretroviral Therapy

    OpenAIRE

    Luetkemeyer, Anne F.; Havlir, Diane V.; Currier, Judith S.

    2010-01-01

    There is growing interest in the pathogenesis, treatment, and prevention of long-term complications of HIV disease and its therapies. Specifically, studies focused on cardiovascular, renal, bone, and fat abnormalities were prominent at the 17th Conference on Retroviruses and Opportunistic Infections. Although enthusiasm about the effectiveness of current antiretroviral therapy remains strong, collectively, the ongoing work in the area of HIV disease and treatment complications appears to refl...

  12. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment

    DEFF Research Database (Denmark)

    Olsen, Mette Frahm; Abdissa, Alemseged; Kæstel, Pernille

    2014-01-01

    Objectives: To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months....../µL (−2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients...... with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. Conclusions: Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements...

  13. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study: a phase-II randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Montoya Carlos J

    2009-06-01

    Full Text Available Abstract Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients or placebo (55 patients. Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on

  14. Scientific rationale for antiretroviral therapy in 2005: viral reservoirs and resistance evolution.

    Science.gov (United States)

    Siliciano, Robert F

    2005-01-01

    Hope for a cure for HIV-1 infection was dampened by the discovery of a latent form of the virus that persists in resting CD4+ cells. This reservoir of latently HIV-infected resting memory T cells represents an archive of viral genotypes produced in an individual from the onset of infection. Entry into the reservoir is stopped with suppressive antiretroviral therapy, but the archived viruses are capable of re-initiating active infections, are released continuously from this reservoir, and can cause viral rebound if antiretroviral therapy is stopped. Studies of residual low-level viremia (Robert F. Siliciano, MD, PhD, at the International AIDS Society-USA course in New York in March 2005.

  15. Acute Liver Failure among Patients on Efavirenz-Based Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Innocent Lule Segamwenge

    2018-01-01

    Full Text Available Objectives. To describe the clinical characteristics of patients presenting with fulminant liver failure after varying periods of exposure to Efavirenz containing antiretroviral medications. Methods. We report a series of 4 patients with human immunodeficiency virus (HIV infection who were admitted with acute liver failure (ALF over a 6-month period. All these patients had been treated with a range of Efavirenz containing antiretroviral regimens and were negative for hepatitis A, B, and C infections as well as other opportunistic infections, all were negative for autoimmune hepatitis, and none had evidence of chronic liver disease or use of alcohol or herbal medications. Information on patient clinical characteristics, current antiretroviral regimen, CD4 count, HIV-1 RNA levels, and clinical chemistry parameters was collected. Informed consent was provided. Results. During a 6-month period, four patients without other known risk factors for acute hepatitis presented with symptomatic drug-induced liver injury with varying symptoms and outcomes. The pattern of liver injury was hepatocellular for all the 4 cases. Liver biopsies were done for all the four cases and the results showed a heavy mixed inflammatory cell infiltrate with eosinophils. For three patients withdrawal of Efavirenz from their antiretroviral regimen was sufficient to restore transaminase levels to normal and led to improvement of clinical symptoms. For one patient his clinical course was characterized by fulminant liver failure and fluctuating episodes of hepatic encephalopathy which ultimately resulted in his death. Conclusion. Hepatotoxicity of Efavirenz is not as rare as previously described in the literature and does actually present with fatal outcomes. The key message to note is that frequent monitoring of liver enzymes should be done at initiation of antiretroviral therapy and should continue throughout the treatment period.

  16. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

    2003-01-01

    , a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral...... to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...

  17. Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

    Science.gov (United States)

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D’Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan AC

    2014-01-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235

  18. Antiretroviral Therapy during the Neonatal Period | Nuttall | Southern ...

    African Journals Online (AJOL)

    Initiation of combination antiretroviral therapy (cART) at 6–9 weeks of age has been shown to reduce early infant mortality by 76% and HIV progression by 75% compared with cART deferred until clinical or CD4 criteria were met. In the landmark Children with HIV Early Antiretroviral Therapy (CHER) trial, although the ...

  19. Class of Antiretroviral Drugs and the Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Reiss, P; Sabin, CA

    2007-01-01

    BACKGROUND: We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infarction. It is not clear whether this association differs according to the class of antiretroviral drugs. We conducted a study to investigate the association of cumu...

  20. Nurses' perceptions about Botswana patients' anti-retroviral therapy ...

    African Journals Online (AJOL)

    Anti-retroviral drugs(ARVs) are supplied free of charge in Botswana. Lifelong adherence to antiretroviral therapy (ART) is vital to improve the patient's state of well-being and to prevent the development of strains of the human immunodefi ciency virus (HIV) that are resistant to ART. Persons with ART-resistant strains of HIV ...

  1. Exploration of pain in children on antiretroviral treatment in a ...

    African Journals Online (AJOL)

    Exploration of pain in children on antiretroviral treatment in a regional hospital in South Africa. M Azam, L Campbell, A Ross. Abstract. Background: Patients with human immunodeficiency virus (HIV) disease on antiretroviral therapy (ART) may experience pain for a variety of reasons, including the effects of the virus itself, ...

  2. New targets and novel antiretrovirals | Wood | Southern African ...

    African Journals Online (AJOL)

    Highly active antiretroviral therapy (HAART) has to date been based on use of a triple combination of drugs chosen from three classes of antiretrovirals (ARVs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). These ARV classes ...

  3. Accessing antiretroviral therapy for children: Caregivers' voices

    Directory of Open Access Journals (Sweden)

    Margaret (Maggie Williams

    2016-10-01

    Full Text Available Despite efforts to scale up access to antiretroviral therapy (ART, particularly at primary health care (PHC facilities, antiretroviral therapy (ART continues to be out of reach formany human immunodeficiency virus (HIV-positive children in sub-Saharan Africa. In resource limited settings decentralisation of ART is required to scale up access to essential medication. Traditionally, paediatric HIV care has been provided in tertiary care facilities which have better human and material resources, but limited accessibility in terms of distance for caregivers of HIV-positive children. The focus of this article is on the experiences of caregivers whilst accessing ART for HIV-positive children at PHC (decentralised care facilities in Nelson Mandela Bay (NMB in the Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual research design was used. The target population comprised caregivers of HIV-positive children. Data were collected by means of indepth individual interviews, which were thematically analysed. Guba's model was usedto ensure trustworthiness. Barriers to accessing ART at PHC clinics for HIV-positive children included personal issues, negative experiences, lack of support and finance, stigma and discrimination. The researchers recommend standardised programmes be developed and implemented in PHC clinics to assist in providing treatment, care and support for HIV positive children.

  4. Accessing antiretroviral therapy for children: Caregivers' voices

    Directory of Open Access Journals (Sweden)

    Margaret (Maggie Williams

    2016-12-01

    Full Text Available Despite efforts to scale up access to antiretroviral therapy (ART, particularly at primary health care (PHC facilities, antiretroviral therapy (ART continues to be out of reach for many human immunodeficiency virus (HIV-positive children in sub-Saharan Africa. In resource limited settings decentralisation of ART is required to scale up access to essential medication. Traditionally, paediatric HIV care has been provided in tertiary care facilities which have better human and material resources, but limited accessibility in terms of distance for caregivers of HIV-positive children. The focus of this article is on the experiences of caregivers whilst accessing ART for HIV-positive children at PHC (decentralised care facilities in Nelson Mandela Bay (NMB in the Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual research design was used. The target population comprised caregivers of HIV-positive children. Data were collected by means of in-depth individual interviews, which were thematically analysed. Guba's model was used to ensure trustworthiness. Barriers to accessing ART at PHC clinics for HIV-positive children included personal issues, negative experiences, lack of support and finance, stigma and discrimination. The researchers recommend standardised programmes be developed and implemented in PHC clinics to assist in providing treatment, care and support for HIV-positive children.

  5. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  6. Rates of inappropriate antiretroviral prescription among injection drug users

    Directory of Open Access Journals (Sweden)

    Bonner Simon

    2007-01-01

    Full Text Available Abstract Background Although the survival benefits of antiretroviral therapy (ART for the treatment of HIV infection are well established, the clinical management of HIV disease continues to present major challenges. There are particular concerns regarding access to appropriate HIV treatment among HIV-infected injection drug users (IDU. Methods In a prospective cohort study of HIV-infected IDU in Vancouver, Canada, we examined initial ART regimens vis-à-vis the provincial government's therapeutic guidelines at the time ART was initiated. Briefly, there have been four sets of guidelines: Era 1 (1992 to November 1995; double-drug (dual NRTIs ART for patients with a CD4 cell count of 350 or less; Era 2 (December 1995 to May 1996; double-drug therapy for patients with a CD4+ cell count of 500 or less; Era 3 (June 1996 to June 1997; triple-drug therapy (dual NRTIs with a PI or NNRTI for patients who had a plasma viral load of > 100,000 HIV-1 RNA copies/mL; dual therapy with two NRTIs for those with a plasma viral load of 5,000 to 100,000 HIV-1 RNA copies/mL; Era 4 (since July 1997; universal use of triple drug therapy as first-line treatment. Results Between May 1996 and May 2003, 431 HIV-infected individuals were enrolled into the cohort. By May 31, 2003, 291 (67.5% individuals had initiated ART. We noted instances of inappropriate antiretroviral prescription in each guideline era, with 9 (53% in Era 1, 3 (12% in Era 2, 22 (28% in Era 3, and 23 (15% in Era 4. Of the 57 subjects who received an inappropriate ART regimen initially, 14 never received the appropriate therapy; among the remaining 43, the median time to the initiation of a guideline-appropriate ART regimen was 12 months (inter-quartile range 5 – 20. Conclusion The present study identified measurable rates of guideline-inappropriate ART prescription for patients who were injection drug users. Rates were highest in the era of dual therapy, although high rates persisted into the triple

  7. Technology-based self-care methods of improving antiretroviral adherence: a systematic review.

    Directory of Open Access Journals (Sweden)

    Parya Saberi

    Full Text Available As HIV infection has shifted to a chronic condition, self-care practices have emerged as an important topic for HIV-positive individuals in maintaining an optimal level of health. Self-care refers to activities that patients undertake to maintain and improve health, such as strategies to achieve and maintain high levels of antiretroviral adherence.Technology-based methods are increasingly used to enhance antiretroviral adherence; therefore, we systematically reviewed the literature to examine technology-based self-care methods that HIV-positive individuals utilize to improve adherence. Seven electronic databases were searched from 1/1/1980 through 12/31/2010. We included quantitative and qualitative studies. Among quantitative studies, the primary outcomes included ARV adherence, viral load, and CD4+ cell count and secondary outcomes consisted of quality of life, adverse effects, and feasibility/acceptability data. For qualitative/descriptive studies, interview themes, reports of use, and perceptions of use were summarized. Thirty-six publications were included (24 quantitative and 12 qualitative/descriptive. Studies with exclusive utilization of medication reminder devices demonstrated less evidence of enhancing adherence in comparison to multi-component methods.This systematic review offers support for self-care technology-based approaches that may result in improved antiretroviral adherence. There was a clear pattern of results that favored individually-tailored, multi-function technologies, which allowed for periodic communication with health care providers rather than sole reliance on electronic reminder devices.

  8. Health and federal budgetary effects of increasing access to antiretroviral medications for HIV by expanding Medicaid.

    Science.gov (United States)

    Kahn, J G; Haile, B; Kates, J; Chang, S

    2001-09-01

    OBJECTIVES. This study modeled the health and federal fiscal effects of expanding Medicaid for HIV-infected people to improve access to highly active antiretroviral therapy. A disease state model of the US HIV epidemic, with and without Medicaid expansion, was used. Eligibility required a CD4 cell count less than 500/mm3 or viral load greater than 10,000, absent or inadequate medication insurance, and annual income less than $10,000. Two benefits were modeled, "full" and "limited" (medications, outpatient care). Federal spending for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security Income, and Social Security Disability Insurance were assessed. An estimated 38,000 individuals would enroll in a Medicaid HIV expansion. Over 5 years, expansion would prevent an estimated 13,000 AIDS diagnoses and 2600 deaths and add 5,816 years of life. Net federal costs for all programs are $739 million (full benefits) and $480 million (limited benefits); for Medicaid alone, the costs are $1.43 and $1.17 billion, respectively. Results were sensitive to awareness of serostatus, highly active antiretroviral therapy cost, and participation rate. Strategies for federal cost neutrality include Medicaid HIV drug price reductions as low as 9% and private insurance buy-ins. Expansion of the Medicaid eligibility to increase access to antiretroviral therapy would have substantial health benefits at affordable costs.

  9. Current status of topical antiretroviral chemoprophylaxis.

    Science.gov (United States)

    Van Damme, Lut; Szpir, Michael

    2012-11-01

    Recent studies suggest that the vaginal delivery of antiretroviral (ARV) agents - such as tenofovir, dapivirine and UC781 - may be a promising way to reduce the high rates of HIV infection among women in developing countries. This review examines these developments. The Microbicide Trials Network 003 study, a large phase IIb trial, was unable to show that daily dosing with 1% tenofovir vaginal gel was effective for HIV prevention. Nevertheless, preclinical and early-phase clinical trials suggest that ARV drugs - formulated in vaginal gels, rings, films, tablets and diaphragms - could be effective for HIV chemoprophylaxis. Investigations of topical chemoprophylaxis methods have seen mixed results in the past 12-18 months. Product adherence may prove to be one of the field's greatest challenges. Phase II and III trials continue to explore different dosing strategies for topical products that contain one or more ARV agents.

  10. The cost of antiretroviral therapy in Haiti

    Directory of Open Access Journals (Sweden)

    Fitzgerald Daniel W

    2008-02-01

    Full Text Available Abstract Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Conclusion Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.

  11. Manifestações otoneurológicas associadas à terapia anti-retroviral Otoneurological manifestations associated with antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Andrêza Batista Cheloni Vieira

    2008-02-01

    Full Text Available Ototoxicidade e terapia anti-retroviral parecem estar associadas. O objetivo desse estudo foi avaliar essa possível correlação. Foram avaliados 779 prontuários médicos de pacientes infectados pelo HIV e regularmente acompanhados, sendo 162 tratados com terapia anti-retroviral e 122 não tratados (controle. Pacientes em tratamento eram mais velhos (média 42 anos, com maior tempo de confirmação sorológica (80 meses e com menor carga viral (p=0,00. CD4+ foi semelhante entre os grupos (P=0,60. No grupo tratado, três (1,8% casos de perda auditiva idiopática e dois (1,3% de perda auditiva relacionada a otosclerose foram observadas e ambas iniciadas após terapia anti-retroviral. Nenhuma diferença estatística relacionada à perda auditiva idiopática foi encontrada entre os grupos. Enquanto estudos descritivos consideram possível ototoxidade associada à terapia anti-retroviral, esse possível efeito adverso não foi relacionado à terapia anti-retroviral neste estudo. Contrariamente, otosclerose poderia estar correlacionada à terapia anti-retroviral. Este assunto merece ser estudado.Ototoxicity and antiretroviral therapy seem to be associated. The aim of this study was to evaluate this possible correlation. Evaluations were carried out on 779 medical records from HIV-infected patients who were being regularly followed up, of whom 162 were being treated with antiretroviral therapy and 122 were untreated (controls. The patients undergoing treatment were older (mean: 42 years, had had serological confirmation for longer times (80 months and had smaller viral loads (P = 0.00. CD4+ was similar between the groups (P = 0.60. In the treated group, three cases (1.8% of idiopathic hearing loss and two (1.3% of otosclerosis-related hearing loss were observed, which both started after antiretroviral therapy. No statistical difference relating to idiopathic hearing loss was found between the groups. While descriptive studies consider possible

  12. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

    Science.gov (United States)

    Grinsztejn, Beatriz; Hosseinipour, Mina C; Ribaudo, Heather J; Swindells, Susan; Eron, Joseph; Chen, Ying Q; Wang, Lei; Ou, San-San; Anderson, Maija; McCauley, Marybeth; Gamble, Theresa; Kumarasamy, Nagalingeshwaran; Hakim, James G; Kumwenda, Johnstone; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; de Melo, Marineide Gonçalves; Mayer, Kenneth H; Eshleman, Susan H; Piwowar-Manning, Estelle; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Sanne, Ian; Gallant, Joel; Hoffman, Irving; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Havlir, Diane; Cohen, Myron S

    2014-01-01

    Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group

  13. Reduced Hepatitis B Virus (HBV)-Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

    OpenAIRE

    Chang, J. Judy; Wightman, Fiona; Bartholomeusz, Angeline; Ayres, Anna; Kent, Stephen J.; Sasadeusz, Joseph; Lewin, Sharon R.

    2005-01-01

    Functional hepatitis B virus (HBV)-specific T cells are significantly diminished in individuals chronically infected with HBV compared to individuals with self-limiting HBV infection or those on anti-HBV therapy. In individuals infected with human immunodeficiency virus type 1 (HIV-1), coinfection with HBV is associated with an increased risk of worsening liver function following antiviral therapy and of more rapid HBV disease progression. Total HBV-specific T-cell responses in subjects with ...

  14. The effects of enhanced access to antiretroviral therapy: a qualitative ...

    African Journals Online (AJOL)

    The effects of enhanced access to antiretroviral therapy: a qualitative study of community perceptions in ... Twenty FGDs comprising of 190 participants and 12 KI interviews were conducted. ... All data was tape recorded with consent from

  15. Short-term treatment outcomes of children starting antiretroviral ...

    African Journals Online (AJOL)

    Short-term treatment outcomes of children starting antiretroviral therapy in the intensive care unit, general medical wards and outpatient HIV clinics at Red Cross War Memorial Children's Hospital, Cape Town, South Africa: A retrospective cohort study.

  16. Adherence to antiretrovirals in refugees and asylum seekers.

    Science.gov (United States)

    Nwoguh, Francisca

    Adherence to antiretroviral regimes is essential in effective management of HIV. The cultural, social, religious and immigration status of refugees and asylum seekers can have an impact on their understanding of their care needs and maintenance of their treatment regimen.

  17. Roles of family dynamics on adherence to highly active antiretroviral ...

    African Journals Online (AJOL)

    EB

    Background: Adherence to highly active antiretroviral therapy (HAART) has been proven .... Table 1: Relationship between socio-demographic characteristics and HAART adherence among ... constraints (44%), stigma (15%), travel/migration.

  18. Antiretroviral Drug Resistance- implications for HIV/AIDS reduction ...

    African Journals Online (AJOL)

    Saharan Africa and other developing countries. ... Abstract: Background: The introduction of the highly active antiretroviral therapy in the mid-1990s has significantly reduced morbidities and prolonged the lifespan of people living with HIV. However ...

  19. Why HIV Positive Patients on Antiretroviral Treatment and/or ...

    African Journals Online (AJOL)

    Why HIV Positive Patients on Antiretroviral Treatment and/or Cotrimoxazole Prophylaxis Use Traditional Medicine: Perceptions of Health Workers, Traditional Healers and Patients: A Study in Two Provinces of South Africa.

  20. Anti-retroviral therapy induced diabetes in a Nigerian | Bakari ...

    African Journals Online (AJOL)

    African Health Sciences ... Background:Anti-retroviral therapy (ART) using Highly Active Anti-retroviral Therapy (HAART) has led to ... HIV infected individuals on one hand, and side effects of chronic administration of these drugs on the other.

  1. Antiretroviral therapy in a community clinic - early lessons from a ...

    African Journals Online (AJOL)

    Antiretroviral therapy in a community clinic - early lessons from a pilot project. ... The HIV Research Unit, University of Cape Town, supplied training and ... Attention must be given to the diagnosis of tuberculosis during screening and early ART ...

  2. Long-Acting Antiretrovirals: Where Are We now?

    Science.gov (United States)

    Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O

    2017-04-01

    Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

  3. A clinical assessment of antiretroviral-treated patients Referred from ...

    African Journals Online (AJOL)

    HAART) on the immunological, virological and clinical status of two groups of patients in the South African government antiretroviral (ARV) programme in KwaZulu-Natal, viz. patients previously treated with ARVs in the private sector and then ...

  4. Antiretroviral Drugs Used in the Treatment of HIV Infection

    Science.gov (United States)

    ... HIV/AIDS Treatment Antiretroviral drugs used in the treatment of HIV infection Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Drugs Used in the Treatment of HIV Infection All FDA-approved medicines used in the ...

  5. Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Eric S Rosenberg

    2010-05-01

    Full Text Available An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation.Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log(10 HIV-1 RNA copies/mL, respectively.The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of

  6. Scientific Production about the Adherence to Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Regina Célia De Oliveira

    2017-09-01

    Full Text Available Objective: To identify the elite of authors about the subject adherence to antiretroviral therapy; to identify the journals turned to publishing articles about adherence to antiretroviral therapy; and to identify and analyze the most commonly used words in abstracts of articles about adherence to antiretroviral therapy. Method: A bibliometric study conducted through the Scopus base. We used articles published between 1996 and 2014, after application of the eligibility criteria, there were composed the sample with 24 articles. The data were analyzed descriptively. Were used the laws of bibliometric (Lotka, Bradford and Zipf and the conceptual cloud map of words, through the program Cmap tools. Results: Lotka's Law identified the 5 authors more productive (46% of the total published. Bradford is impaired in this study. Concerning Zipf, 3 zones were determined, 31.47% of the words with in the first zone, 26.46% in the second and 42.06% in the third. In the conceptual map, the words/factors that positively and negatively influence adherence were emphasized, among them the need for more research in the health services. Conclusion: There are few publications about the accession to antiretroviral therapy, and the scientific production is in the process of maturation. One can infer that the theme researched is not yet an obsolete topic. It should be noted that the Bibliometric was a relevant statistic tool to generate information about the publications about the antiretroviral therapy. Descriptors: Antiretroviral Therapy, Highly Active; Medication Adherence; Bibliometric; HIV; Acquired Immunodeficiency Syndrome

  7. Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

    Science.gov (United States)

    Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

    2016-03-01

    To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

  8. Barriers to initiation of antiretrovirals during antituberculosis therapy in Africa.

    Directory of Open Access Journals (Sweden)

    Dominique J Pepper

    2011-05-01

    Full Text Available In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB. The initiation of antiretroviral therapy (ART during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART.Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years who commenced TB therapy, were eligible for ART, and were followed for 6 months.Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25-43% did not initiate ART. Male gender and younger age (<36 years were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25-10.95] and 3.3 [95%CI: 1.12-9.69], respectively. Death during TB therapy was associated with a CD4+ count <100 cells/µL.In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients--particularly young men--did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.

  9. Virologic outcomes in early antiretroviral treatment: HPTN 052.

    Science.gov (United States)

    Eshleman, Susan H; Wilson, Ethan A; Zhang, Xinyi C; Ou, San-San; Piwowar-Manning, Estelle; Eron, Joseph J; McCauley, Marybeth; Gamble, Theresa; Gallant, Joel E; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kalonga, Ben; Pilotto, Jose H; Grinsztejn, Beatriz; Godbole, Sheela V; Chotirosniramit, Nuntisa; Santos, Breno Riegel; Shava, Emily; Mills, Lisa A; Panchia, Ravindre; Mwelase, Noluthando; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Fogel, Jessica M

    2017-05-01

    The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm 3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4  1000 copies/mL > 24 weeks after ART initiation. Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

  10. Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

    NARCIS (Netherlands)

    Caniglia, Ellen C.; Cain, Lauren E.; Sabin, Caroline A.; Robins, James M.; Logan, Roger; Abgrall, Sophie; Mugavero, Michael J.; Hernández-Díaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard D.; Reiss, Peter; van Sighem, Ard; Mathews, William C.; del Amo, Julia; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Justice, Amy C.; Tate, Janet P.; Gill, John; Pacheco, Antonio; Veloso, Valdilea G.; Bucher, Heiner C.; Egger, Matthias; Furrer, Hansjakob; Porter, Kholoud; Touloumi, Giota; Crane, Heidi; Miro, Jose M.; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

    2017-01-01

    Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. In this observational study, we used data from prospective

  11. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

    Science.gov (United States)

    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-09-03

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general

  12. Interactions between recreational drugs and antiretroviral agents.

    Science.gov (United States)

    Antoniou, Tony; Tseng, Alice Lin-In

    2002-10-01

    To summarize existing data regarding potential interactions between recreational drugs and drugs commonly used in the management of HIV-positive patients. Information was obtained via a MEDLINE search (1966-August 2002) using the MeSH headings human immunodeficiency virus, drug interactions, cytochrome P450, medication names commonly prescribed for the management of HIV and related opportunistic infections, and names of commonly used recreational drugs. Abstracts of national and international conferences, review articles, textbooks, and references of all articles were also reviewed. Literature on pharmacokinetic interactions was considered for inclusion. Pertinent information was selected and summarized for discussion. In the absence of specific data, prediction of potential clinically significant interactions was based on pharmacokinetic and pharmacodynamic properties. All protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors are substrates and potent inhibitors or inducers of the cytochrome P450 system. Many classes of recreational drugs, including benzodiazepines, amphetamines, and opioids, are also metabolized by the liver and can potentially interact with antiretrovirals. Controlled interaction studies are often not available, but clinically significant interactions have been observed in a number of case reports. Overdoses secondary to interactions between the "rave" drugs methylenedioxymethamphetamine (MDMA) or gamma-hydroxybutyrate (GHB) and PIs have been reported. PIs, particularly ritonavir, may also inhibit metabolism of amphetamines, ketamine, lysergic acid diethylmide (LSD), and phencyclidine (PCP). Case series and pharmacokinetic studies suggest that nevirapine and efavirenz induce methadone metabolism, which may lead to symptoms of opiate withdrawal. A similar interaction may exist between methadone and the PIs ritonavir and nelfinavir, although the data are less consistent. Opiate metabolism can be inhibited or induced by

  13. Remission of HIV-associated myelopathy after highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Fernandez-Fernandez F

    2004-07-01

    Full Text Available HIV-associated myelopathy is the leading cause of spinal cord disease in HIV-infected patients. Typically, it affects individuals with low CD4 T cell counts, presenting with slowly progressive spastic paraparesis associated with dorsal column sensory loss as well as urinary disturbances. Other aetiologies must be first ruled out before establishing the diagnosis. We report here the case of a 37-year-old woman with advanced HIV disease, who developed HIV-associated myelopathy. The patient showed a gradual improvement after beginning with highly active antiretroviral therapy and, finally, she achieved a complete functional recovery. In addition, neuroimaging and neurophysiological tests normalized.

  14. Scaling-up antiretroviral therapy in Malawi.

    Science.gov (United States)

    Jahn, Andreas; Harries, Anthony D; Schouten, Erik J; Libamba, Edwin; Ford, Nathan; Maher, Dermot; Chimbwandira, Frank

    2016-10-01

    In Malawi, health-system constraints meant that only a fraction of people infected with human immunodeficiency virus (HIV) and in immediate need of antiretroviral treatment (ART) received treatment. In 2004, the Malawian Ministry of Health launched plans to scale-up ART nationwide, adhering to the principle of equity to ensure fair geographical access to therapy. A public health approach was used with standardized training and treatment and regular supervision and monitoring of the programme. Before the scale-up, an estimated 930 000 people in Malawi were HIV-infected, with 170 000 in immediate need of ART. About 3000 patients were on ART in nine clinics. By December 2015, cumulatively 872 567 patients had been started on ART from 716 clinics, following national treatment protocols and using the standard monitoring system. Strong national leadership allowed the ministry of health to implement a uniform system for scaling-up ART and provided benchmarks for implementation on the ground. New systems of training staff and accrediting health facilities enabled task-sharing and decentralization to peripheral health centres and a standardized approach to starting and monitoring ART. A system of quarterly supervision and monitoring, into which operational research was embedded, ensured stocks of drug supplies at facilities and adherence to national treatment guidelines.

  15. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    Science.gov (United States)

    Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

    2015-06-01

    CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.

  16. Antiretroviral procurement and supply chain management.

    Science.gov (United States)

    Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril

    2014-01-01

    Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products.

  17. Acceptability of Early Antiretroviral Therapy Among South African Women.

    Science.gov (United States)

    Garrett, Nigel; Norman, Emily; Leask, Kerry; Naicker, Nivashnee; Asari, Villeshni; Majola, Nelisile; Karim, Quarraisha Abdool; Karim, Salim S Abdool

    2018-03-01

    WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22-30), in a 10 year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was 217 cells/µl (range 135-372) before 2010, and increased to 531 cells/µl (range 272-1095) by 2015 (p suppression rates at 3, 6, 12 and 18 months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24-33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6 months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.

  18. Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

    Directory of Open Access Journals (Sweden)

    Nadia Bakkour

    2007-10-01

    Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

  19. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  20. 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...

  1. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: A combined analysis of 12 mathematical models

    NARCIS (Netherlands)

    J.W. Eaton (Jeffrey); D. Menzies; J. Stover (John); V. Cambiano (Valentina); L. Chindelevitch (Leonid); A. Cori (Anne); J.A.C. Hontelez (Jan); S. Humair (Salal); C.C. Kerr (Cliff); D.J. Klein (David); S. Mishra (Sharmistha); K.M. Mitchell (Kate); B.E. Nichols (Brooke); K. Vickerman; R. Bakker (Roel); T. Bärnighausen (Till); A. Bershteyn (Anna); D.E. Bloom (David); M-C. Boily (Marie-Claude); S.T. Chang (Stewart); T. Cohen (Ted); P. Dodd (Peter); C. Fraser (Christophe); C. Gopalappa (Chaitra); J. Lundgren (Jens); N.K. Martin (Natasha); T.S. Mikkelsen; E. Mountain (Elisa); Q.D. Pham (Quang); T. Pickles (Tom); A. Phillips (Andrew); S. Platt; C. Pretorius (Carel); H.J. Prudden (Holly); J.A. Salomon (Joshua); D.A.M.C. van de Vijver (David); S.J. de Vlas (Sake); B.G. Wagner (Bradley); R.G. White (Richard); D.C. Wilson (David); L. Zhang (Lingling); J. Blandford (John); G. Meyer-Rath (Gesine); M. Remme (Michelle); P. Revill (Paul); N. Sangrujee (Nalinee); F. Terris-Prestholt (Fern); M.C. Doherty (Meg); N. Shaffer (Nathan); P.J. Easterbrook (Philippa); G. Hirnschall (Gottfried); T.B. Hallett (Timothy)

    2014-01-01

    textabstractBackground: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for

  2. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

  3. [Sustainability of Brazilian policy for access to antiretroviral drugs].

    Science.gov (United States)

    Grangeiro, Alexandre; Teixeira, Luciana; Bastos, Francisco I; Teixeira, Paulo

    2006-04-01

    The expense of acquiring antiretroviral drugs in Brazil has given rise to debate about the sustainability of the policy of universal access to AIDS medications, despite the evident benefits. The objective of this study was to analyze the evolution of the Ministry of Health's spending on acquiring antiretroviral drugs from 1998 to 2005, the determining factors and the medium-term sustainability of this policy (2006-2008). The study on the evolution of spending on antiretrovirals included analysis of their prices, the year-by-year expenditure, the number of patients utilizing the medication, the mean expenditure per patient and the strategies for reducing the prices maintained during this period. To analyze the sustainability of the policy for access to antiretrovirals, the cost of acquiring the drugs over the period from 2006 to 2008 was estimated, along with the proportion of gross domestic product and federal health expenditure represented by this spending. The data were collected from the Ministry of Health, the Brazilian Institute for Geography and Statistics (IBGE) and the Ministry of Planning. The expenditure on antiretrovirals increased by 66% in 2005, breaking the declining trend observed over the period from 2000 to 2004. The main factors associated with this increase were the weakening of the national generics industry and the unsatisfactory results from the process of negotiating with pharmaceutical companies. The Brazilian policy for universal access is unsustainable at the present growth rates of the gross domestic product, unless the country compromises its investments in other fields.

  4. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

    Science.gov (United States)

    Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John; Cambiano, Valentina; Chindelevitch, Leonid; Cori, Anne; Hontelez, Jan A C; Humair, Salal; Kerr, Cliff C; Klein, Daniel J; Mishra, Sharmistha; Mitchell, Kate M; Nichols, Brooke E; Vickerman, Peter; Bakker, Roel; Bärnighausen, Till; Bershteyn, Anna; Bloom, David E; Boily, Marie-Claude; Chang, Stewart T; Cohen, Ted; Dodd, Peter J; Fraser, Christophe; Gopalappa, Chaitra; Lundgren, Jens; Martin, Natasha K; Mikkelsen, Evelinn; Mountain, Elisa; Pham, Quang D; Pickles, Michael; Phillips, Andrew; Platt, Lucy; Pretorius, Carel; Prudden, Holly J; Salomon, Joshua A; van de Vijver, David A M C; de Vlas, Sake J; Wagner, Bradley G; White, Richard G; Wilson, David P; Zhang, Lei; Blandford, John; Meyer-Rath, Gesine; Remme, Michelle; Revill, Paul; Sangrujee, Nalinee; Terris-Prestholt, Fern; Doherty, Meg; Shaffer, Nathan; Easterbrook, Philippa J; Hirnschall, Gottfried; Hallett, Timothy B

    2014-01-01

    New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per

  5. Poor functional immune recovery in aged HIV-1-infected patients following successfully treatment with antiretroviral therapy.

    Science.gov (United States)

    Kasahara, Taissa M; Hygino, Joana; Andrade, Regis M; Monteiro, Clarice; Sacramento, Priscila M; Andrade, Arnaldo F B; Bento, Cleonice A M

    2015-10-01

    Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  6. HIV INFECTION, ANTIRETROVIRAL THERAPY AND CARDIOVASCULAR RISK

    Directory of Open Access Journals (Sweden)

    Katleen de Gaetano Donati

    2010-11-01

    Full Text Available In the last 15 years, highly active antiretroviral therapy (HAART has determined a dramatic reduction of both morbidity and mortality in human immunodeficiency virus (HIV-infected subjects, transforming this infection in a chronic and manageable disease. Patients surviving with HIV in the developed world, in larger number men,  are becoming aged. As it would be expected for a population of comparable age, many HIV-infected individuals report a family history of cardiovascular disease, a small proportion have already experienced a cardiovascular event and an increasing proportion has diabetes mellitus. Smoking rate is very high while an increasing proportion of HIV-infected individuals have dyslipidaemia. Studies suggest that these traditional risk factors could play an important  role in the development of cardiovascular disease in these patients as they do in the general population. Thus, whilst the predicted 10-year cardiovascular disease risk remains relatively low at present, it will likely increase in relation to the progressive aging of  this patient population. Thus, the long-term follow-up of HIV infected patients has to include co-morbidity management such as cardiovascular disease prevention and treatment. Two intriguing aspects related to the cardiovascular risk in patients with HIV infection are the matter of current investigation: 1 while these subjects share many cardiovascular risk factors with the general population, HIV infection itself increases cardiovascular risk; 2 some HAART regimens too influence atherosclerotic profile, partly due to lipid changes. Although the mechanisms involved in the development of cardiovascular complications in HIV-infected patients remain to be fully elucidated, treatment guidelines recommending interventions to prevent cardiovascular disease in these individuals are already available; however, their application is still limited.

  7. Factors influencing global antiretroviral procurement prices.

    Science.gov (United States)

    Wirtz, Veronika J; Forsythe, Steven; Valencia-Mendoza, Atanacio; Bautista-Arredondo, Sergio

    2009-11-18

    Antiretroviral medicines (ARVs) are one of the most costly parts of HIV/AIDS treatment. Many countries are struggling to provide universal access to ARVs for all people living with HIV and AIDS. Although substantial price reductions of ARVs have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global ARV prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on ARV procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to ARV programs. An ARV-medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 ARVs, global median prices and price variation were calculated. Linear regression models for each ARV were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Three key factors appear to have an influence on a country's ARV prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President's Emergency Plan For AIDS Relief. One of the principal mechanisms that can help to lower prices for ARV over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful tool to achieve this.

  8. The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Sinha Sanjeev

    2011-11-01

    Full Text Available Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV and tuberculosis (TB co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART when co-administered with rifampicin-containing antituberculosis treatment (ATT and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1% patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83 at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10, 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08, 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10 respectively and 3.04 μg/ml (in cases. Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in

  9.  The potential nephrotoxicity of antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2012-09-01

    Full Text Available  The intensive studies carried out in many scientific laboratories and the efforts of numerous pharmaceutical companies have led to the development of drugs which are able to effectively inhibitHIV proliferation. At present, a number of antiretroviral agents with different mechanisms of actionare available. Unfortunately, long-term use of antiretroviral drugs, however, does not remainindifferent to the patient and can cause significant side effects.In the present work, the antiretroviral drugs with a nephrotoxicity potential most commonly usedin clinical practice are described. In the review attention has also been focused on the nephropathyresulting from the HIV infection alone and the influence of genetic factors on the occurrenceof pathological changes in the kidney.

  10. Predictors of mortality among HIV infected patients taking antiretroviral treatment in Ethiopia: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Biadgilign Sibhatu

    2012-05-01

    Full Text Available Abstract Background Studies indicate that there is high early mortality among patients starting antiretroviral treatment in sub-Saharan Africa. However, there is paucity of evidence on long term survival of patients on anti-retroviral treatment in the region. The objective of this study is to examine mortality and its predictors among a cohort of HIV infected patients on anti-retroviral treatment retrospectively followed for five years. Methods A retrospective cohort study was conducted among HIV infected patients on ART in eastern Ethiopia. Cox regression and Kaplan-Meier analyses were performed to investigate factors that influence time to death and survival over time. Result A total of 1540 study participants were included in the study. From the registered patients in the cohort, the outcome of patients as active, deceased, lost to follow up and transfer out was 1005 (67.2%, 86 (5.9%, 210 (14.0% and 192 (12.8% respectively. The overall mortality rate provides an incidence density of 2.03 deaths per 100 person years (95% CI 1.64 - 2.50. Out of a total of 86 deaths over 60 month period; 63 (73.3% died during the first 12 months, 10 (11.6% during the second year, and 10 (11.6% in the third year of follow up. In multivariate analysis, the independent predictors for mortality were loss of more 10% weight loss, bedridden functional status at baseline, ≤ 200 CD4 cell count/ml, and advanced WHO stage patients. Conclusion A lower level of mortality was detected among the cohort of patients on antiretroviral treatment in eastern Ethiopia. Previous history of weight loss, bedridden functional status at baseline, low CD4 cell count and advanced WHO status patients had a higher risk of death. Early initiation of ART, provision of nutritional support and strengthening of the food by prescription initiative, and counseling of patients for early presentation to treatment is recommended.

  11. Adherence to anti-retroviral drugs in pregnant and lactating HIV ...

    African Journals Online (AJOL)

    Background: Anti-retroviral drugs reduce morbidity and mortality due to HIV and prevent transmission from mother to child. But compliance on anti-retroviral treatment is an essential element for the success of therapeutic goals. Objective: To assess the level of compliance of anti-retroviral treatment in pregnant and lactating ...

  12. Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

    Directory of Open Access Journals (Sweden)

    Justin Cohen

    2017-08-01

    Full Text Available With the advent of highly active antiretroviral therapy (HAART survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer’s disease (AD, we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs. Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.

  13. Neurocognitive function in HIV infected patients on antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Alan Winston

    Full Text Available To describe factors associated with neurocognitive (NC function in HIV-positive patients on stable combination antiretroviral therapy.We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT trial.NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND. Global z-scores (NPZ-5 were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD below population means in at least two domains (abnormal Frascati score calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression.Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD baseline and nadir CD4+ lymphocyte counts were 553(217 and 177(117 cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR NPZ-5 score was -0.5 (-1.2/-0 overall, and -0.3 (-0.7/0.1 and -1.4 (-2/-0.8 in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001, but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20. In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001.In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised.ClinicalTrials.gov, NCT01230580.

  14. Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection.

    Directory of Open Access Journals (Sweden)

    Masahiko Mori

    Full Text Available The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female; and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p<0.001. Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively. However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%, ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001. The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002. These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex.

  15. In vivo assessment of antiretroviral therapy-associated side effects

    Directory of Open Access Journals (Sweden)

    Eduardo Milton Ramos-Sanchez

    2014-07-01

    Full Text Available Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

  16. Avances recientes en VIH/SIDA: Terapia antiretroviral.

    Directory of Open Access Journals (Sweden)

    Ernesto Scerpella

    1997-01-01

    Full Text Available Recent advances in our understanding of HIV infection in patients with the acquired immunodeficiency syndrome (AIDS are leading us to explore new treatment strategies, including the use of combination antiretroviral therapy. In this review, we present information from recently completed clinical trials explore the use of combination therapy, including ACTG 175, the Delta studies, and the NUCA studies. In addition, we present preliminary about use of protease inhibitors, the newest class of antiretrovirals. (Rev Med Hered 1997; 8: 23-31.

  17. Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.

    Science.gov (United States)

    Schader, Susan M; Colby-Germinario, Susan P; Schachter, Jordana R; Xu, Hongtao; Wainberg, Mark A

    2011-08-24

    To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC(50)s) and combined effects were determined by calculating combination indices. Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI(50) = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI(50) = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI(50) = 0.968) and NNRTI-resistant (CI(50) = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.

  18. Repression of Proteases and Hsp90 Chaperone Expression Induced by an Antiretroviral in Virulent Environmental Strains of Cryptococcus neoformans.

    Science.gov (United States)

    Serafin, Cleber Fernando; Paris, Ana Paula; Paula, Claudete Rodrigues; Simão, Rita Cássia Garcia; Gandra, Rinaldo Ferreira

    2017-04-01

    This study evaluated the effect of the antiretroviral ritonavir on protease secretion in different strains of Cryptococcus neoformans isolated from the environment and investigated the expression of heat shock protein (Hsp90), classically described virulence factors in other yeast in the presence of the same antiretroviral. The presence of the enzyme was detected by the formation of a degradation of the halo around the colonies. The results were classified as follows: level 1 (without proteases), level 2 (positive for proteases), and level 3 (strongly positive for proteases). Total protein extract isolated from the cell walls of the 12 strains incubated in the absence and presence of ritonavir (0.3125 mg mL -1 ) were resolved by SDS-PAGE and analyzed by Western blot assays using an antiserum against Hsp90 from Blastocladiella emersonii. All strains tested showed inhibition of proteinase activity in the presence of ritonavir at 0.3125 to 1.25 mg mL -1 . High levels of Hsp90 were observed in the absence of ritonavir (0.3125 mg mL -1 ), except for the non-virulent control cells. In contrast, in the presence of the antiretroviral, a drastic reduction in the expression of the chaperone was observed. The data suggest that ritonavir, in addition to containing viral replication, could inhibit the expression of virulence factors in opportunistic yeast, as proteases and Hsp90. According to our current knowledge, this is the first time that the inhibition of Hsp90 by an antiretroviral was reported for environmental isolates of C. neoformans.

  19. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

    Science.gov (United States)

    Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

    2016-01-01

    IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory

  20. Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome.

    Science.gov (United States)

    Rasmussen, Thomas A; McMahon, James; Chang, J Judy; Symons, Jori; Roche, Michael; Dantanarayana, Ashanti; Okoye, Afam; Hiener, Bonnie; Palmer, Sarah; Lee, Wen Shi; Kent, Stephen J; Van Der Weyden, Carrie; Prince, H Miles; Cameron, Paul U; Lewin, Sharon R

    2017-08-24

    To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4 T cells. Case report. Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing. HIV-hepatitis B virus coinfection was diagnosed and antiretroviral therapy initiated 4 years prior to presentation with Sezary syndrome and primary cutaneous anaplastic large cell lymphoma. The patient received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length HIV-DNA sequencing demonstrated multiple defective viruses but no identical or expanded sequences. Alemtuzumab extensively depleted T cells, including more than 1 log reduction in total T cells and more than 3 log reduction in CD4 T cells. Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained detectable at low levels even after depletion of nearly all CD4 T cells. Alemtuzumab extensively depleted multiple T-cell subsets and decreased the frequency of but did not eliminate HIV-infected CD4 T cells. Studying the effects on HIV persistence following immune recovery in HIV-infected individuals who require alemtuzumab for malignancy or in animal studies may provide further insights into novel cure strategies.

  1. Personal barriers to antiretroviral therapy adherence: Case studies ...

    African Journals Online (AJOL)

    Personal barriers to antiretroviral therapy adherence: Case studies from a rural Uganda prospective clinical cohort. ... Journal Home > Vol 13, No 2 (2013) > ... should target specific personal barriers to ART adherence like: lack of family support, health and sexual life concerns, desire to have children and family instability.

  2. Case Report: A man on antiretroviral therapy with painful thighs

    African Journals Online (AJOL)

    A 54 year old man presented with increasing pain in both thighs for three months during a follow up visit at the antiretroviral therapy (ART) clinic of Queen Elizabeth. Central Hospital. He was first seen at the same clinic three years and eight months before the current presentation, when he started. ART with ...

  3. Effect Of Acess To Antiretroviral Therapy On Stigma, Jimma

    African Journals Online (AJOL)

    JU

    with HIV/AIDS was low 45 (16.6%) when compared with the fear of being stigmatized (perceived stigma) which was195 (72.2%). ... attitudinal change on stigma with access to antiretroviral treatment. There was a statistically significant association ..... All other ethnicities and nationalities. § PLWHA on follow up but not started ...

  4. Providing insecticide treated bed nets in antiretroviral treatment ...

    African Journals Online (AJOL)

    HIV-replication.5-13 Mathematical models show that repeated ... antiretroviral treatment clinics in Malawi: a pilot ... related disease or AIDS.3 In addition, there are between 300 - ... and growing evidence of interactive pathology.1,2. HIV ..... by the HIV Unit and its partners. ... procurement and supply chain systems developed.

  5. Efficacy and durability of nevirapine in antiretroviral drug naive patients

    NARCIS (Netherlands)

    Lange, Joep M. A.

    2003-01-01

    Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) naive patients. Four key studies have

  6. When to start antiretroviral therapy in infants and children | Cotton ...

    African Journals Online (AJOL)

    We review the background and key studies that inform decisions on when to initiate antiretroviral therapy (ART) in infants and children. The World Health Organization staging system from 2006 was based on conditions commonly seen in Africa and provided an impetus for advancing ART in children. Because of poor ...

  7. Quality of Life and Adherence to Antiretroviral Drugs

    African Journals Online (AJOL)

    Sitwala

    Department of Nursing Sciences, School of Medicine, University of Zambia, Lusaka, Zambia. ABSTRACT ... it is individually, socially and culturally determined. .... concept that is a semantic representation which .... antiretroviral drugs enhances quality of life and is clearly in keeping with the philosophy of palliative. 19 care .

  8. When to start antiretroviral therapy in infants and children

    Directory of Open Access Journals (Sweden)

    Mark F Cotton

    2009-12-01

    Full Text Available This articles provides a background for antiretroviral therapy in infants and children, incorporating both old and new data. There is increasing data favouring early therapy for all age groups. Below a year of age, all HIV-infected infants should commence therapy and thereafter at higher CD4 thresholds than previous recommendations

  9. HIV Testing and Antiretroviral Therapy Initiation at Birth: Views from ...

    African Journals Online (AJOL)

    HIV Testing and Antiretroviral Therapy Initiation at Birth: Views from a Primary Care Setting in Khayelitsha. A Nelson, J Maritz, J Giddy, L Frigati, H Rabie, G van Cutsem, T Mutseyekwa, N Jange, J Bernheimer, M Cotton, V Cox ...

  10. Religion, authority and their interplay in the shaping of antiretroviral ...

    African Journals Online (AJOL)

    The article explores how religious actors have increasingly shaped the nature of antiretroviral treatment (ART) services in Kabarole district, western Uganda. As have the regular health services, Christian donors, non-governmental organisations (NGOs), and churches in the district have also stepped up to provide money for ...

  11. Abuse of antiretroviral drugs combined with addictive drugs by ...

    African Journals Online (AJOL)

    Reports of the use of antiretroviral drugs (ARVs) to produce a highly addictive drug called nyaope or whoonga are of major concern as ARVs are easily accessible in sub-Saharan Africa, including to pregnant women. Use of illicit drugs by pregnant women may result in serious adverse effects in their infants. We have ...

  12. Spirituality and adherence to antiretroviral drugs among HIV positive ...

    African Journals Online (AJOL)

    Method: It was an observational, longitudinal study in which 215 consenting HIV positive patients aged 18 to 65 years who were on antiretroviral drugs were recruited through systematic random sampling technique. Socio-demographic characteristics, clinical history and physical examination findings were documented for ...

  13. Accessibility of antiretroviral therapy in Ghana: Convenience of access

    African Journals Online (AJOL)

    Joyce Addo-Atuah * Joyce Addo-Atuah, BPharm, MSc, PhD, Assistant Professor, Touro College of Pharmacy, New York, USA. She was a PhD candidate at the University of Tennessee (UT), Memphis, USA, when the study was undertaken in Ghana. joyce.addo-atuah@touro.edu, Dick Gourley Dick Gourley, PharmD, Professor and Dean, UT College of Pharmacy during the study and major research advisor. , Greta Gourley Greta Gourley, PharmD/PhD, retired Associate Professor of Pharmaceutical Sciences at UT College of Pharmacy and research advisor. , Shelley I. White-Means Shelley I. White-Means, PhD, Professor and Chair, Health Outcomes and Policy Research Division of UT College of Pharmacy at time of the study and research advisor. , Robin J. Womeodu Robin J. Womeodu, MD, F.A.C.P., Associate Professor of Internal Medicine and Preventive Medicine at UT College of Medicine at time of study and research advisor. , Richard J. Faris Richard J. Faris, Assistant Professor at UT College of Pharmacy at time of study and research advisor. &

    2012-05-30

    May 30, 2012 ... The accuracy of any instructions, formulae, and drug doses ... The convenience of accessing antiretroviral therapy (ART) is ...... tious diseases, paediatrics, chest diseases, dermatology, public .... CD4 count, (2) a full blood count, (3) a liver function test, (4) ..... America: measures of the African brain drain.

  14. Pharmacoepidemiology of antiretroviral drugs in a teaching hospital ...

    African Journals Online (AJOL)

    Objective: Prescribing, adherence, and adverse drug events to HAART in a large antiretroviral programme in Lagos was evaluated. Design: A retrospective 5 year open cohort study. Setting: The AIDS Prevention Initiative in Nigeria (APIN) clinic at LUTH is one of the United States Presidential Emergency Plan for AIDS ...

  15. HIV-related symptoms and management in HIV and antiretroviral ...

    African Journals Online (AJOL)

    Karl Peltzer

    2014-01-03

    Jan 3, 2014 ... To cite this article: Karl Peltzer (2013) HIV-related symptoms and management in HIV and antiretroviral therapy patients ...... Fear/worry. 14.2. 22. 2.5. 20 ..... Internalized Stigma, Discrimination, and Depression among Men and.

  16. Antiretroviral drug resistance: A guide for the southern African clinician

    African Journals Online (AJOL)

    Both private and public sector see a bewildering clinical array of patients taking failing antiretroviral (ARV) regimens. We intend this article to provide a practical guide to help clinicians understand and manage ARV drug resistance in an African context. ARV resistance is a rapidly evolving field, requiring expertise in dealing ...

  17. The influence of antiretroviral treatment on willingness to test: a ...

    African Journals Online (AJOL)

    Previous quantitative studies suggest a mutually reinforcing relationship between HIV counselling and testing (HCT) and antiretroviral treatment (ART). HCT is the entry into ART, and access to ART appears to increase HIV-testing uptake in settings with historically low uptake. Adopting a qualitative approach, this study ...

  18. The intersection of antiretroviral therapy, peer support programmes ...

    African Journals Online (AJOL)

    Evidence suggests that interventions for people living with HIV infection that include, in combination, antiretroviral therapy (ART), peer support and economic empowerment are likely to be more effective than if used alone. We report a qualitative study in West Nile Uganda that explored perceptions of HIV stigma among ...

  19. End-user centeredness in antiretroviral therapy services in Nigerian ...

    African Journals Online (AJOL)

    Objective: To describe the perception of end users with regard to end-user centeredness in antiretroviral therapy (ART) service provision in Nigerian public health facilities. Design: A qualitative design was followed. Subjects and setting: Unstructured focus group discussions were conducted with end users (n = 64) in six ...

  20. Christian identity and men's attitudes to antiretroviral therapy in ...

    African Journals Online (AJOL)

    Increasing access to antiretroviral therapy (ART), especially in urban areas in Zambia, has transformed the landscape of the HIV epidemic to include hope. Drawing upon long-term ethnographic research, this article briefly describes the religious ideas of a cohort of former students of a Catholic mission boarding school for ...

  1. Correlates of highly active antiretroviral therapy adherence among ...

    African Journals Online (AJOL)

    Correlates of highly active antiretroviral therapy adherence among urban Ethiopian clients. ... clients' self-reported adherence to HAART medication, a descriptive, comparative cross-sectional study was carried out among adults receiving HAART medication at the Zewditu Memorial Hospital ART clinic in Addis Ababa.

  2. Timing of antiretroviral therapy initiation in adults with HIV ...

    African Journals Online (AJOL)

    Timing of antiretroviral therapy initiation in adults with HIV-associated tuberculosis: Outcomes of therapy in an urban hospital in KwaZulu-Natal. ... We aimed to compare clinical outcomes of patients with HIV-associated TB who commenced ART at different stages of TB therapy. Methods. A retrospective chart review was ...

  3. Malarial infection among HIV Patients on Antiretroviral Therapy (ART)

    African Journals Online (AJOL)

    Malarial infection among patients on antiretroviral therapy (ART) attending Federal Medical Centre, Makurdi, Benue State was investigated between April and August 2008 to determine the level of malaria infection in HIV/AIDS patients on ART and those not on ART with respect to CD4+ counts, age and gender. A total of ...

  4. Differences in access and patient outcomes across antiretroviral ...

    African Journals Online (AJOL)

    Objective. To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. Design. Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across ...

  5. Patients' perceptions of a rural decentralised anti-retroviral therapy ...

    African Journals Online (AJOL)

    Background: Geographical and financial barriers hamper accessibility to HIV services for rural communities. The government has introduced the nurse initiated management of anti-retroviral therapy at primary health care level, in an effort to improve patient access and reduce patient loads on facilities further up the system.

  6. Delays in switching patients onto second-line antiretroviral treatment ...

    African Journals Online (AJOL)

    Background: South Africa has one of the largest antiretroviral treatment (ART) programmes globally. In addition to increasing access to ART, it is important that the health system also focuses on the appropriate management of patients who fail first-line ART. Delays in switching patients onto second-line ART can adversely ...

  7. Modelling the relationship between antiretroviral treatment and HIV ...

    African Journals Online (AJOL)

    This paper shows how two publicly available epidemiological modelling packages, namely the Spectrum AIDS Impact Model and the ASSA2003 AIDS and Demographic Model, predict very different impacts from rolling out highly active antiretroviral treatment (HAART) on new HIV infections. Using South Africa as a case ...

  8. Estimates of eligibility for antiretroviral treatment (ART) and ...

    African Journals Online (AJOL)

    The study assessed the proportion of HIV-infected educators that need antiretroviral treatment (ART) according to current criteria, and estimated the impact of ART on AIDS mortality by modelling scenarios with and without access to ART. Specimens for HIV testing were obtained from 17 088 educators and a sub-sample of ...

  9. adherence to antiretroviral treatment in Zambia: a qualitative study

    African Journals Online (AJOL)

    Patients\\' adherence to antiretroviral therapy (ART) is important for effective medical treatment of HIV/AIDS. We conducted a qualitative interview study in the Copperbelt Province of Zambia in 2006. The aim of the study was to explore patients\\' and health care professionals\\' perceived barriers and facilitators to patients\\' ...

  10. Implementation and effectiveness of antiretroviral therapy in Greenland

    DEFF Research Database (Denmark)

    Lohse, N.; Ladefoged, K.; Obel, N.

    2008-01-01

    Analyses from the Danish HIV Cohort Study showed that, despite comparable economic means and general education of healthcare personnel, antiretroviral treatment of HIV in Greenland began later and has been implemented at a slower pace with lower therapeutic effectiveness than in Denmark. However...

  11. Roles of family dynamics on adherence to highly active antiretroviral ...

    African Journals Online (AJOL)

    Background: Adherence to highly active antiretroviral therapy (HAART) has been proven to be the only effective treatment for HIV/AIDS worldwide. Good adherence to HAART might require good family support. Objective: To determine the family dynamics and social support of people living with HIV/AIDS (PLWHA) and its ...

  12. Malaria in immuno-suppressed individuals on antiretroviral therapy ...

    African Journals Online (AJOL)

    Malaria in immuno-suppressed individuals on antiretroviral therapy (ART) in north-central Nigeria. C.R. Pam, B.T. Abubakar, G.O. Inwang, G.A. Amuga. Abstract. The immune deficiency caused by HIV infection reduces the immune response to malaria parasitaemia and therefore leads to an increased frequency of clinical ...

  13. Estimation of adult antiretroviral treatment coverage in South Africa ...

    African Journals Online (AJOL)

    The unmet need for treatment in adults is estimated using a Markov model of HIV progression in adults, combined with estimates of annual new HIV infections from a national AIDS and demographic model. Results. By the middle of 2008, 568 000 adults and children were receiving antiretroviral treatment in South Africa, ...

  14. Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort

    DEFF Research Database (Denmark)

    Borges, Álvaro H; Hoy, Jennifer; Florence, Eric

    2017-01-01

    Background: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. Methods: EuroSIDA participants were followed to assess...

  15. A qualitative analysis of the barriers to antiretroviral therapy initiation ...

    African Journals Online (AJOL)

    A qualitative analysis of the barriers to antiretroviral therapy initiation among children 2 to 18 months of age in Swaziland. Charisse V Ahmed, Pauline Jolly, Luz Padilla, Musa Malinga, Chantal Harris, Nobuhle Mthethwa, Inessa Ba, Amy Styles, Sarah Perry, Raina Brooks, Florence Naluyinda-Kitabire, Makhosini Mamba, ...

  16. among People Receiving Antiretroviral Treatment in Western Uganda

    African Journals Online (AJOL)

    In this paper, we use survey (n=87) and interview (n=30) data to investigate orientations towards future childbearing among people receiving antiretroviral treatment and their family members in western Uganda. We investigate how reproductive options are perceived, by those receiving treatment and those closest to them, ...

  17. Quality of Life and Adherence to Antiretroviral Drugs | Mweemba ...

    African Journals Online (AJOL)

    Efficacy of antiretroviral treatment in HIV/AIDS is showing inhibition of viral replication and reduction of viral load to a point where viral particles are undetectable in the blood of infected individuals. ... Quality of life is a complex broad ranging multidimensional concept defined in terms of individual's subjective experiences.

  18. Can measuring immunity to HIV during antiretroviral therapy (ART ...

    African Journals Online (AJOL)

    The vexing issue of whether the immune system can be reconstituted during HIV infection by supplying antiretroviral therapy (ART) has been a question asked about HIV-infected adults and children receiving therapy.1-9 Knowing that the immune system is sufficiently plastic in adults to show restoration of specific and ...

  19. Antiretroviral treatment uptake in patients with HIV associated TB ...

    African Journals Online (AJOL)

    Background. Delivery of integrated care for patients with HIV-associated TB is challenging. We assessed the uptake and timing of antiretroviral treatment (ART) among eligible patients attending a primary care service with co-located ART and TB clinics. Methods. In a retrospective cohort study, all HIV-associated TB patients ...

  20. Determinants of Adherence to Antiretroviral Treatment among HIV ...

    African Journals Online (AJOL)

    This study investigated factors of adherence to Antiretroviral Treatment (ART), factors or variables that can discriminate between adherent and non-adherent patients on ART were selected. Simple structured questionnaire was employed. The study sample consisted of 145 HIV patients who received ART in the Shashemene ...

  1. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1

    DEFF Research Database (Denmark)

    Raffi, François; Babiker, Abdel G; Richert, Laura

    2014-01-01

    BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. METHODS: Between August, 2010......-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. FUNDING: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories....

  2. Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

    DEFF Research Database (Denmark)

    Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette

    2002-01-01

    In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...

  3. TRIM5α association with cytoplasmic bodies is not required for antiretroviral activity

    International Nuclear Information System (INIS)

    Song, Byeongwoon; Diaz-Griffero, Felipe; Park, Do Hyun; Rogers, Thomas; Stremlau, Matthew; Sodroski, Joseph

    2005-01-01

    The tripartite motif (TRIM) protein, TRIM5α, restricts infection by particular retroviruses. Many TRIM proteins form cytoplasmic bodies of unknown function. We investigated the relationship between cytoplasmic body formation and the structure and antiretroviral activity of TRIM5α. In addition to diffuse cytoplasmic staining, the TRIM5α proteins from several primate species were located in cytoplasmic bodies of different sizes; by contrast, TRIM5α from spider monkeys did not form cytoplasmic bodies. Despite these differences, all of the TRIM5α proteins exhibited the ability to restrict infection by particular retroviruses. Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5α-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection. Studies of green fluorescent protein-TRIM5α fusion proteins indicated that no TRIM5α domain is specifically required for association with cytoplasmic bodies. Apparently, the formation of cytoplasmic bodies is not required for the antiretroviral activity of TRIM5α

  4. Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Bernaschi Massimo

    2009-10-01

    Full Text Available Abstract Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART. Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

  5. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  6. Hematological alterations and thymic function in newborns of HIV-infected mothers receiving antiretroviral drugs.

    Science.gov (United States)

    Wongnoi, Rotjanee; Penvieng, Nawaporn; Singboottra, Panthong; Kingkeow, Doungnapa; Oberdorfer, Peninnah; Sirivatanapa, Pannee; Pornprasert, Sakorn

    2013-06-08

    To investigate the effects of antiretroviral (ARV) drugs on hematological parameters and thymic function in HIV-uninfected newborns of HIV-infected mothers. Cross sectional study. Chiang-Mai University Hospital, Chiang-Mai, Thailand. 49 HIV-uninfected and 26 HIV-infected pregnancies. Cord blood samples of newborns from HIV-uninfected and HIV-infected mothers were collected. Hematological parameters were measured using automatic blood cell count. T-cell receptor excision circles (TRECs) levels in cord blood mononuclear cells (CBMCs), CD4+ and CD8+ T-cells were quantified using real-time PCR.. Hemotological parameters and thymic function. Newborn of HIV-infected mother tended to have lower mean levels of hemoglobin than those of HIV-uninfected mother (137 ±22 vs 146 ±17 g/L, P = 0.05). Furthermore, mean of red blood cell (RBC) counts and hematocrit and median of TRECs in CD4+ T-cells in the newborns of the former were significantly lower than those of the latter [3.6 ±0.7 vs 4.8 ±0.6 x 1012 cells/L, P cells) in HIV-uninfected newborns of HIV-infected mothers.

  7. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis.

    Science.gov (United States)

    Petersen, Maya L; Wang, Yue; van der Laan, Mark J; Guzman, David; Riley, Elise; Bangsberg, David R

    2007-10-01

    Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. Data were obtained from an observational cohort of 245 human immunodeficiency virus (HIV)-infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. Pillbox organizer use was estimated to improve adherence by 4.1%-4.5% and was associated with a decrease in viral load of 0.34-0.37 log10 copies/mL and a 14.2%-15.7% higher probability of achieving a viral load organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of approximately $19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.

  8. Incidence of HIV-associated tuberculosis among individuals taking combination antiretroviral therapy: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Tendesayi Kufa

    Full Text Available Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis.Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy.From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI 3.39-5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23-0.69 per 100 person-years] with significant heterogeneity observed between the studies.Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis.

  9. Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction.

    Directory of Open Access Journals (Sweden)

    Reneé de Waal

    Full Text Available BACKGROUND: Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART. Both are assumed to be antiretroviral adverse drug reactions. METHODS: We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. RESULTS: Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs showed more limb fat loss (or less fat gain with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs; efavirenz (versus protease inhibitors (PIs; and NRTI-containing (versus NRTI-sparing. RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. CONCLUSIONS: There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.

  10. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

    Science.gov (United States)

    Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

    1999-02-04

    Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

  11. Relationship between antiretrovirals used as part of a cART regimen and CD4 count increases in patients with suppressed viremia

    DEFF Research Database (Denmark)

    Mocroft, A; Phillips, A; Ledergerber, B

    2006-01-01

    consecutive measurements with VL points according to nucleoside backbones and other antiretrovirals used. METHODS: Generalized linear models, accounting for multiple measurements within patients, were used to compare CD4 cell count changes after adjustment for antiretrovirals, time...... to the boosted-protease inhibitor regimen (n = 5915), use of an abacavir-based triple-nucleoside regimen was associated with a lower annual change in CD4 cell count (n = 2504 pairs; -26.1/microl; P = 0.011). CONCLUSIONS: A nucleoside backbone of zidovudine/lamivudine or any tenofovir-based backbone...... was associated with significantly poorer increases in CD4 cell count compared to a nucleoside backbone of stavudine/lamivudine, as was an abacavir-based triple nucleoside regimen compared to a boosted protease inhibitor regimen. Long-term studies are needed to determine whether the differences in immunological...

  12. First-line antiretroviral drug discontinuations in children.

    Directory of Open Access Journals (Sweden)

    Melony Fortuin-de Smidt

    Full Text Available There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.We included children (<16 years at ART initiation who initiated ≥3 antiretrovirals between 2004-2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.We included 3579 children with median follow-up duration of 41 months (IQR 14-72. At ART initiation, median age was 44 months (IQR 13-89 and median CD4 percent was 15% (IQR 9-21%. At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%, treatment failure (18%, treatment simplification (5%, drug interactions (3%, and other or unspecified reasons (18%. The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2-55.4, 1.6 (0.5-4.8, 2.0 (1.2-3.3, and 1.3 (0.6-2.8 per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.While stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with

  13. Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy.

    Science.gov (United States)

    Agudelo-Hernandez, Arcadio; Chen, Yue; Bullotta, Arlene; Buchanan, William G; Klamar-Blain, Cynthia R; Borowski, Luann; Riddler, Sharon A; Rinaldo, Charles R; Macatangay, Bernard J C

    2017-09-24

    We evaluated the subclinical shedding of six different herpesviruses in antiretroviral drug-treated HIV-positive [HIV(+)] MSM, and determined how this is associated with markers of inflammation and immune activation. We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T-cell reconstitution, and 12 age-matched HIV-negative [HIV (-)] MSM from the Multicenter AIDS Cohort Study at four timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8. T-cell activation and plasma levels of soluble markers of inflammation and activation were also measured at the corresponding timepoints. HIV(+) participants had a trend for higher total herpesvirus shedding rate. HIV(+) participants also had a significantly higher rate of shedding EBV and CMV compared with the HIV(-) group. Herpesvirus shedding was mostly seen in throat washings. In the HIV(+) group, herpesvirus shedding rate inversely correlated with plasma levels of interferon γ-induced protein 10 and soluble CD163. CMV DNA levels negatively correlated with levels of T-cell activation. There was a trend for a positive correlation between EBV shedding rate and plasma soluble CD14. HHV6 shedding rate negatively correlated with plasma levels of interleukin-6, soluble CD163, and interferon gamma-induced protein 10. Correlations were not observed among HIV(-) individuals. Among treated HIV-infected MSM, there are higher subclinical shedding rates of some herpesviruses that occur in different body compartments and negatively correlate with levels of inflammation and immune activation.

  14. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    NARCIS (Netherlands)

    Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C; Niesters, Bert

    2008-01-01

    OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between

  15. Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

    Science.gov (United States)

    Baker, Jason V; Sharma, Shweta; Achhra, Amit C; Bernardino, Jose Ignacio; Bogner, Johannes R; Duprez, Daniel; Emery, Sean; Gazzard, Brian; Gordin, Jonathan; Grandits, Greg; Phillips, Andrew N; Schwarze, Siegfried; Soliman, Elsayed Z; Spector, Stephen A; Tambussi, Giuseppe; Lundgren, Jens

    2017-05-22

    HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4 + cell counts >500 cells/mm 3 . Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm 3 , an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in

  16. [Child with HIV/AIDS: perception of the antiretroviral treatment].

    Science.gov (United States)

    da Motta, Maria da Graça Corso; Pedro, Eva Neri Rubim; Neves, Eliane Tatsch; Issi, Helena Becker; Ribeiro, Nair Regina Ritter; Wachholz, Neiva Isabel Raffo; Greff, Aramita Prates; Ribeiro, Aline Cammarano; de Paula, Cristiane Cardoso; Coelho, Débora Fernandes; de Padoin, Stela Maris Mello; Kreitchmann, Regis; Kruel, Aline Goulart; Poletto, Paula Manoela Batista

    2012-12-01

    This article presents a cutting from the multicentric study carried out in the municipalities of Porto Alegre and Santa Maria/ RS with the objective of unveiling the perception and the life experience of the child regarding the antiretroviral treatment. With qualitative approach, the study was carried out with seven children of five to ten years of age, in the period from 2006 to 2010, after approval by Committee National for Ethics in research and the Committees of Ethics in research. Based on the thematic analysis was obtained the results: the day-to-day life of the child with medicines; the family care upon the adhesion to the antiretroviral treatment; the professional care:perception of children with infection. Observation showed that the children face adversities, know and appreciate the treatment in spite of the paradoxical movement of rejection/acceptance expressed by the fight against the syndrome.

  17. Antiretroviral therapy during the neonatal period

    African Journals Online (AJOL)

    2015-05-04

    May 4, 2015 ... until clinical or CD4 criteria were met.1 In the landmark Children with HIV Early ... to cART regimens aimed at long-term treatment requires further investigation. ... therefore be a consideration for short-term use in neonatal ...... of memory B cells and the longevity of humoral responses in HIV-1 vertically-.

  18. Multiple parasitic and viral infections in a patient living with HIV/AIDS on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    K Deepika

    2017-01-01

    Full Text Available Patients with human immunodeficiency virus (HIV infection are more prone for gastrointestinal infections causing diarrhoea, particularly with parasites. Parasitic infections have been regularly reported in such patients. A female patient confirmed positive for HIV 1 on antiretroviral therapy came with complaints of chronic diarrhoea for the past 7 months. Her initial CD4 count was 89 cells/μl of blood, and antibodies to cytomegalovirus and herpes simplex virus 1 and 2 virus were found to be positive in the patient's serum, but there was no HIV-associated retinopathy. Her stool examination showed decorticated fertilised eggs of Ascaris lumbricoides, cysts of Blastocystis sp. and Entamoeba species in the unconcentrated sample and oocysts of Cystoisospora species, egg of Schistosoma haematobium and eggs of Trichuris trichiura in the concentrated. The patient responded well to cotrimoxazole and albendazole, and repeat samples were negative for all these parasites.

  19. Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Costagliola, Dominique

    2009-01-01

    OBJECTIVE: We examined survival and prognostic factors of patients who developed HIV-associated non-Hodgkin lymphoma (NHL) in the era of combination antiretroviral therapy (cART). DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. METHODS: We included all cART-naive patients......-seven patients (72%) from 22 cohorts met inclusion criteria. Survival at 1 year was 66% [95% confidence interval (CI) 63-70%] for systemic NHL (n = 763) and 54% (95% CI: 43-65%) for primary brain lymphoma (n = 84). Risk factors for death included low nadir CD4 cell counts and a history of injection drug use...... with primary brain lymphoma. More advanced immunodeficiency is the dominant prognostic factor for mortality in patients with HIV-related NHL....

  20. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals

    DEFF Research Database (Denmark)

    Kunisaki, Ken M; Niewoehner, Dennis E; Collins, Gary

    2016-01-01

    BACKGROUND: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV...... Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per μL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants...... were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5...

  1. Persistent inflammation and endothelial activation in HIV-1 infected patients after 12 years of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Frederikke F Rönsholt

    Full Text Available The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART.Inflammation and endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL 8, tumor necrosis factor α (TNFα, vascular cell adhesion molecule-1 (sVCAM-1, intercellular adhesion molecule-1 (sICAM-1, sE-Selectin, and sP-Selectin.HIV infected patients had higher levels of β2-microglobulin, IL-8, TNFα, and sICAM-1 than uninfected controls, and HIV infected patients lacked correlation between platelet counts and sP-Selectin levels found in uninfected controls.Discrete signs of systemic and vascular inflammation persist even after very long term cART.

  2. Access to antiretroviral drugs and AIDS management in Senegal.

    Science.gov (United States)

    Desclaux, Alice; Ciss, Mounirou; Taverne, Bernard; Sow, Papa S; Egrot, Marc; Faye, Mame A; Lanièce, Isabelle; Sylla, Omar; Delaporte, Eric; Ndoye, Ibrahima

    2003-07-01

    Description and analysis of the Senegalese Antiretroviral Drug Access Initiative (ISAARV), the first governmental highly active antiretroviral therapy (HAART) treatment programme in Africa, launched in 1998. ISAARV was initially an experimental project designed to evaluate the feasibility, efficacy and acceptability of HAART in an African context. It was based on four principles: collective definition of the strategy, with involvement of the health professionals who would be called on to execute the programme; matching the objectives to available means (gradual enrollment according to drug availability); monitoring by several research programmes; and ongoing adaptation of treatment and follow-up according to the latest international recommendations. Persons qualifying for antiretroviral (ARV) therapy are selected on the basis of immunological and clinical criteria, regardless of economic and social considerations. A system of subsidies was created to favor access to ARV. Following the ARV price reductions that occurred in November 2000, 100% subsidies were created for the poorest participants. Optimal adherence was ensured by monthly follow-up by pharmacists and support groups held by social workers and patient associations. The chosen supply and distribution system allowed drug dispensing to be strictly controlled. The ISAARV programme demonstrates that HAART can be successfully prescribed in Africa. This experience has served as the basis for the creation of a national treatment programme in Senegal planned to treat 7000 patients by 2006.

  3. Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders.

    Science.gov (United States)

    Mijch, A; Burgess, P; Judd, F; Grech, P; Komiti, A; Hoy, J; Lloyd, J H; Gibbie, T; Street, A

    2006-05-01

    adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.

  4. Efek Samping Obat terhadap Kepatuhan Pengobatan Antiretroviral Orang dengan HIV/AIDS

    OpenAIRE

    Latif, Fachri; Maria, Ida Leida; Syafar, Muhammad

    2014-01-01

    Tingkat kepatuhan pengobatan antiretroviral di Indonesia sangat rendah, yaitu 40 - 70%, yang masih di bawah target nasional dengan tingkat kepatuhan 95%. Berbeda dengan rata-rata nasional, Puskesmas Jumpandang Baru justru memiliki tingkat kepatuhan pengobatan antiretroviral pasien HIV/AIDS di atas 95%. Penelitian ini bertujuan untuk menganalisis faktor yang paling berpengaruh terhadap kepatuhan pengobatan antiretroviral orang dengan HIV/AIDS (ODHA). Jenis penelitian bersifat observasional ana...

  5. The effects of antiretroviral therapy on HIV-positive individuals in Wakiso District, Uganda

    OpenAIRE

    Yang, Tina Yang

    2015-01-01

    AIM The aim was to explore the experiences of HIV-positive individuals before and after gaining access to antiretroviral therapy in Wakiso District, Uganda and how antiretroviral therapy impacts certain aspects of those living with HIV, such as sexual behavior, support systems, faith and personal identity. METHODS Based on secondary data analysis of “Life On Antiretroviral Therapy: People’s Adaptive Coping And Adjustment To Living With HIV As A Chronic Condition In Wakiso District, Uganda” by...

  6. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a man with AIDS

    Directory of Open Access Journals (Sweden)

    Yoganathan K

    2012-04-01

    Full Text Available Katie Yoganathan1, David Brown2, Kathir Yoganathan31Cardiff Medical School, Cardiff, Wales, UK; 2Virus Reference Department, Microbiology Services, Health Protection Agency, London, UK; 3Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UKAbstract: A 43-year-old Caucasian homosexual man with AIDS presented with blurring of vision, change of personality, and memory loss in March 1999. He had first been admitted 2 months previously for treatment of Pneumocystis jiroveci pneumonia. A magnetic resonance imaging scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema. JC virus was detected by nested polymerase chain reaction in the cerebrospinal fluid. These findings were diagnostic of progressive multifocal leukoencephalopathy (PML. His CD4 count was 34 cells/mL, and his HIV ribonucleic acid level was 800,789 copies/mL. He was treated with a combination antiretroviral therapy. He was last reviewed in October 2011. He was fully independent socially and mentally, but he still had some residual neurologic signs with right-sided homonymous hemianopia and visual agnosia. His HIV ribonucleic acid level was undetectable, and his CD4 count was 574 cells/mm3. Although the median survival of patients with PML was poor before the antiretroviral therapy era, our patient, who is now aged 55 years, is still alive 12 years after the diagnosis. The diagnosis of PML and differential diagnosis of focal neurologic signs in HIV-positive patients are discussed in this case report.Keywords: HIV, focal neurologic signs, cerebral toxoplasmosis, primary brain lymphoma, ischaemic stroke

  7. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    Science.gov (United States)

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  8. Cumulative Antiretroviral Exposure Measured in Hair Is Not Associated With Measures of HIV Persistence or Inflammation Among Individuals on Suppressive ART.

    Science.gov (United States)

    Gandhi, Monica; Gandhi, Rajesh T; Stefanescu, Andrei; Bosch, Ronald J; Cyktor, Joshua C; Horng, Howard; Louie, Alexander; Phung, Nhi; Eron, Joseph J; Hogg, Evelyn; Macatangay, Bernard J C; Hensel, Christopher; Fletcher, Courtney V; Mellors, John W; McMahon, Deborah K

    2018-06-20

    Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation. These findings suggest that higher systemic ARV exposure may not impact HIV persistence or inflammation.

  9. HIV-1 drug resistance in recently HIV-infected pregnant mother's naïve to antiretroviral therapy in Dodoma urban, Tanzania.

    Science.gov (United States)

    Vairo, Francesco; Nicastri, Emanuele; Liuzzi, Giuseppina; Chaula, Zainab; Nguhuni, Boniface; Bevilacqua, Nazario; Forbici, Federica; Amendola, Alessandra; Fabeni, Lavinia; De Nardo, Pasquale; Perno, Carlo Federico; Cannas, Angela; Sakhoo, Calistus; Capobianchi, Maria Rosaria; Ippolito, Giuseppe

    2013-09-21

    HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

  10. In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Brendan A I Payne

    Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

  11. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

    Science.gov (United States)

    Fowler, Mary G; Qin, Min; Fiscus, Susan A; Currier, Judith S; Flynn, Patricia M; Chipato, Tsungai; McIntyre, James; Gnanashanmugam, Devasena; Siberry, George K; Coletti, Anne S; Taha, Taha E; Klingman, Karin L; Martinson, Francis E; Owor, Maxensia; Violari, Avy; Moodley, Dhayendre; Theron, Gerhard B; Bhosale, Ramesh; Bobat, Raziya; Chi, Benjamin H; Strehlau, Renate; Mlay, Pendo; Loftis, Amy J; Browning, Renee; Fenton, Terence; Purdue, Lynette; Basar, Michael; Shapiro, David E; Mofenson, Lynne M

    2016-11-03

    Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than

  12. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    Science.gov (United States)

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy. © The Author(s) 2014.

  13. Antiretroviral treatment switch strategies for lowering the costs of antiretroviral therapy in subjects with suppressed HIV-1 viremia in Spain

    Directory of Open Access Journals (Sweden)

    Llibre JM

    2013-05-01

    Full Text Available Josep M Llibre,1,2 Gloria Cardona,3 José R Santos,2 Angels Andreu,3 Josep O Estrada,4 Jordi Ara,4 Xavier Bonafont,3 Bonaventura Clotet1,21HIV Unit, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 2Lluita contra la SIDA Foundation, Badalona, Barcelona, Spain; 3Hospital Pharmacy, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 4Hospital Management, University Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainBackground: The current economic recession in European countries has forced governments to design emergency measures to reduce spending on drugs, including antiretroviral therapy (ART. Switching antiretroviral drugs for others that have the same efficacy and safety profile at a lower cost (cost-reduction measures, CRM could prove to be a valid means of generating savings.Methods: Descriptive study of prospective consensus-based CRM undertaken in 2011 in a Catalonian hospital HIV unit among patients with prolonged plasma HIV-1 RNA <50 copies/mL.Results: During the study period, we made 673 switches (87.5% more than the previous year, of which 378 (56.2% were CRM (16% of all patients treated, leading to a savings of €87,410/month. Switching tenofovir/emtricitabine for abacavir/lamivudine was the most common CRM (129, 31.3%, followed by simplification to boosted protease inhibitor monotherapy (bPImono, 102, 26%. The CRM that generated the greatest saving were switching to bPImono (38%, withdrawal or replacement of raltegravir (24%, switching tenofovir/emtricitabine for abacavir/lamivudine (13%, and switching to nevirapine (5%. Cost savings with CRM were slightly higher than those achieved with medication paid for by clinical trial sponsors (€80,333/month or through discount arrangements (€76,389/month.Conclusion: Proactively switching antiretroviral therapy in selected treated patients with sustained virological suppression can generate significant cost savings in pharmacy spending in

  14. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; Ledergerber, B

    2010-01-01

    OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategi...

  15. Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study

    DEFF Research Database (Denmark)

    Castillo-Mancilla, Jose R; Phillips, Andrew N; Neaton, James D

    2018-01-01

    Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMAR...

  16. Predictors and Evolution of Antiretroviral Therapy Adherence Among Perinatally HIV-Infected Adolescents in Brazil.

    Science.gov (United States)

    Côté, José; Delmas, Philippe; de Menezes Succi, Regina Célia; Galano, Eliana; Auger, Patricia; Sylvain, Hélène; Colson, Sebastien; Machado, Daisy Maria

    2016-09-01

    Antiretroviral therapy medication adherence is a complex phenomenon influenced by multiple factors. This study examines its evolution and predictors among perinatally HIV-infected youths in São Paulo, Brazil. During a 1-year longitudinal cohort study, perinatally HIV-infected youths aged 13-21 years taking antiretroviral therapy were recruited in hospitals and HIV/AIDS reference centers. Data were collected at baseline and after 12 months. Variables assessed were adherence, self-efficacy regarding medication intake, social support, stress level, depression, CD4 cell count, viral load, and symptoms. Adherence was defined as taking ≥95% of prescribed HIV medication in the past 7 days. Generalized estimating equation and analysis of variance methods were used. A total of 268 adolescents participated in the study (59% female; mean age of 16 years). At baseline, 63.06% of the sample was adherent to their HIV medication, and 52.99% had an undetectable viral load. All participants, regardless of adherence, reported: low levels of stress and symptoms of depression; high perception of medication self-efficacy and social support; and a mean of 6.8 symptoms related to their HIV medication. Predictors of adherence were: high perception of medication self-efficacy (odds ratio = 2.81; 95% confidence interval: 1.94-4.05) and low number of reported medication side effects (odds ratio = .97; 95% confidence interval: .95-.99]. Between baseline and follow-up, 49.6% remained adherent, 22.3% remained nonadherent, and the adherence level changed over time for 28.2%. These findings suggest the need to develop interventions to enhance self-efficacy toward medication and to help youth better manage HIV medication symptoms. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  17. Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

    Directory of Open Access Journals (Sweden)

    Boris Julg

    Full Text Available Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI, tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42% and 83% (95% CI:79%-86% of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3 after 12 and ≥ 500 cells/mm(3 after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001 and nadir CD4 cell count at ART initiation (p<0.0001, while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

  18. Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

    Science.gov (United States)

    Julg, Boris; Poole, Danielle; Ghebremichael, Musie; Castilla, Carmen; Altfeld, Marcus; Sunpath, Henry; Murphy, Richard A; Walker, Bruce D

    2012-01-01

    Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42%) and 83% (95% CI:79%-86%) of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3) after 12 and ≥ 500 cells/mm(3) after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p<0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

  19. Medication possession ratio predicts antiretroviral regimens persistence in Peru.

    Science.gov (United States)

    Salinas, Jorge L; Alave, Jorge L; Westfall, Andrew O; Paz, Jorge; Moran, Fiorella; Carbajal-Gonzalez, Danny; Callacondo, David; Avalos, Odalie; Rodriguez, Martin; Gotuzzo, Eduardo; Echevarria, Juan; Willig, James H

    2013-01-01

    In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

  20. Antiretroviral changes during the first year of therapy

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Policarpo Carmo Sá Bandeira

    Full Text Available Summary Introduction: The Brazilian HIV/AIDS management and treatment guideline (PCDT, published in 2013, recommends and standardizes the use of highly active antiretroviral therapy (HAART in all adult patients, in spite of LTCD4 count. This study aimed to analyze the first year of HAART use in patients from a reference center on HIV/AIDS management in Fortaleza, Ceará. Method: This descriptive study reviewed all prescription forms of antiretroviral regimens initiation and changes from January to July 2014. All antiretroviral regimen changes that occurred during the first year of therapy were evaluated. Data were analyzed with SPSS version 20. Mean, standard deviation and frequency, Student’s t and Mann-Whitney tests calculations were used, with significance at p<0.05. Results: From 527 patients initiating HAART, 16.5% (n=87 had a regimen change in the first year. These patients were mostly male (59.8%; n=52, aged 20 to 39 years, with only one HAART change (72.4%; n=63. Efavirenz was the most often changed drug, followed by tenofovir, zidovudine and lopinavir/ritonavir. Mean time of HAART changes was 120 days, with adverse reactions as the most prevalent cause. HAART was effective in decreasing viral load since second month of treatment (p=0.003 and increasing LTCD4 lymphocytes since fifth month (p<0.001. Conclusion: The main cause of initial HAART changes was adverse reaction and most patients had only one change in the HAART regimen. HAART prescription was in accordance to the PCDT from 2013.

  1. Evaluation of HIV/AIDS patients' knowledge on antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Regina Flávia de Castro Almeida

    Full Text Available Lack of information on antiretroviral drugs or the misunderstanding of available information can facilitate incorrect use of such drugs. This can result in non-adherence to the prescribed regimen, leading to a great possibility of a therapeutic failure. The aim of this study was to know which information HIV/AIDS patients, who receive their medicines at the pharmacy of a reference hospital in the northeast Brazil, have on the drugs they use, the source of this information and whether there is a need for additional information. A total of 195 HIV/AIDS patients, who were using either zidovudina + lamivudina 300+150mg (AZT+3TC, efavirenz 600mg (EFZ or lopinavir/ritonavir 133.33/33mg (LPV/r, were interviewed. The mean age was 41 years (SD = 9.55 and 70.8% were males. Of the total, 55.4% didn't know the effect of the drug in the organism; 35.9% were unaware of the necessity of taking antiretroviral drugs for the rest of their lives; only 14.4% knew how to proceed when a dosage was missed; 22.1% said they could die and the same number of individuals believed in aggravation of the disease in case of treatment interruption. The majority, 68.2%, considered it very necessary to receive drug information. The results show that there is an apparent lack of general information among users of antiretroviral drugs, and at the same time a need for it. It is necessary that all professionals involved in the health care of the patients agree that an efficient supply of information on prescribed drugs is an ethical component of the treatment that favors and fosters its adherence.

  2. The prevalence of metabolic syndrome in Danish patients with HIV infection: the effect of antiretroviral therapy

    DEFF Research Database (Denmark)

    Hansen, B R; Petersen, J; Haugaard, S B

    2009-01-01

    OBJECTIVES: The prevalence of metabolic syndrome (MS) in HIV-infected patients on highly active antiretroviral therapy (HAART) is a subject of debate. We investigated the prevalence of MS in a cohort of Danish HIV-infected patients and estimated the effect of the various classes of antiretroviral...

  3. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy

    NARCIS (Netherlands)

    Pakker, NG; Otto, SA; Hall, D; Wit, FWNM; Hamann, D; van der Ende, Marchina E.; Claessen, FAP; Kauffmann, RH; Koopmans, PP; Sprenger, HG; Weigel, HM; Montaner, JSG; Lange, JMA; Reiss, P; Schellekens, PTA; Miedema, F; Ten Napel, Chris H. H.

    1999-01-01

    Background: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. Objectives: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  4. Improving access to antiretrovirals in rural South Africa – a call to ...

    African Journals Online (AJOL)

    Improving access to antiretrovirals in rural South Africa – a call to action. South Africa (SA) already has the world's biggest antiretroviral (ARV) programme. With the introduction of extended criteria for initiating ARVs, the National Department of Health (NDoH) wishes to increase the number of people on ARVs by around.

  5. The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters

    NARCIS (Netherlands)

    Martinez, Esteban; Visnegarwala, Fehmida; Grund, Birgit; Thomas, Avis; Gibert, Cynthia; Shlay, Judith; Drummond, Fraser; Pearce, Daniel; Edwards, Simon; Reiss, Peter; El-Sadr, Wafaa; Carr, Andrew

    2010-01-01

    Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or

  6. Pregnancy outcome of HIV-infected women on anti-retroviral therapy ...

    African Journals Online (AJOL)

    ... received anti-retroviral treatment at the University of Port Harcourt Teaching Hospital ... 3.8% started in 2nd trimester of pregnancy and 14.1% during labour. ... was minimal and stresses the value of antiretroviral treatment in the prevention of ...

  7. Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Kirk, Ole; Gatell, Jose M

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS: Vi...... rates Udgivelsesdato: 2006/6...

  8. Adverse effects of antiretroviral therapy for HIV infection: a review of selected topics

    NARCIS (Netherlands)

    Nolan, David; Reiss, Peter; Mallal, Simon

    2005-01-01

    In the current era of HIV treatment, the toxicity profiles of antiretroviral drugs have increasingly emerged as a basis for selecting initial antiretroviral regimens as well as a reason for switching therapy in treatment-experienced patients. In this respect, an intensive research effort involving

  9. The status of HIV-1 resistance to antiretroviral drugs in sub-Saharan Africa

    NARCIS (Netherlands)

    Hamers, Raph L.; Derdelinckx, Inge; van Vugt, Michèle; Stevens, Wendy; Rinke de Wit, Tobias F.; Schuurman, Rob

    2008-01-01

    Access to highly active antiretroviral therapy (HAART) for persons infected with HIV in sub-Saharan Africa has greatly improved over the past few years. However, data on long-term clinical outcomes of Africans receiving HAART, patterns of HIV resistance to antiretroviral drugs and implications of

  10. Vietnamese Women's Struggle to Access Antiretroviral Drugs in a Context of Free Treatment

    DEFF Research Database (Denmark)

    Nguyen, Nam Thi Thu; Rasch, Vibeke; Bygbjerg, Ib Christian

    2013-01-01

    This qualitative study aims to explore how HIV positive women living in a northern province of Vietnam experience seeking antiretroviral (ARV) treatment in the public health system, and how they address obstacles encountered along the way. Despite the fact that antiretroviral drugs were freely pr...

  11. Pre-Exposure Prophylaxis and Antiretroviral Resistance: HIV Prevention at a Cost?

    OpenAIRE

    Hurt, Christopher B.; Eron, Joseph J.; Cohen, Myron S.

    2011-01-01

    Prompted by 3 cases of resistance noted in the Pre-Exposure Prophylaxis Initiative and TDF2 trials, we examined literature on mutations elicited by antiretrovirals used for pre-exposure prophylaxis. We discuss signature mutations, how rapidly these emerge, and individual-level and public health consequences of antiretroviral resistance.

  12. Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals

    DEFF Research Database (Denmark)

    Achhra, Amit C; Nugent, Melinda; Mocroft, Amanda

    2016-01-01

    Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted...

  13. Persistent Inflammation and Endothelial Activation in HIV-1 Infected Patients after 12 Years of Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L

    2013-01-01

    The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART).......The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART)....

  14. Effect of Antiretroviral Drug (arved) on the Kidney in Albino Rat ...

    African Journals Online (AJOL)

    African studies on effect of antiretroviral drugs on the kidney are limited resulting to scanty information on the safety of these drugs. This study was therefore designed to evaluate the effects of antiretroviral drugs arved®, on creatinine, urea, potassium and sodium ions as well as histological effect on the kidney. A total of fifty ...

  15. Maternal deaths following nevirapine-based antiretroviral therapy

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    E Bera

    2012-10-01

    Full Text Available We report 2 cases illustrating that it is too simplistic to link nevirapine (NVP toxicity exclusively to individuals with immune preservation. Not enough is known about the mechanism of hepatotoxicity or cutaneous eruption to predict these events. This type of hypersensitivity reaction occurs rarely among HIV-exposed infants taking NVP prophylaxis or antiretroviral therapy (ART-experienced adults with complete plasma viral load suppression. Conversely, HIV-uninfected adults and ART-naive pregnant women appear to be disproportionately affected by the adverse effects of NVP.

  16. Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: effects on leptin and TNF-alpha.

    Science.gov (United States)

    Arjona, M Montes de Oca; Pérez-Cano, R; Garcia-Juárez, R; Martín-Aspas, A; del Alamo, C Fernández Gutiérrez; Girón-González, J A

    2006-04-01

    The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

  17. AIDS-Related Non-Hodgkin's Lymphoma in the Era of Highly Active Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Prakash Vishnu

    2012-01-01

    Full Text Available In economically developed countries, AIDS-related lymphoma (ARL accounts for a large proportion of malignances in HIV-infected individuals. Since the introduction of highly active anti-retroviral therapy (HAART in 1996, epidemiology and prognosis of ARL have changed. While there is a slight increase in the incidence of Hodgkin’s lymphoma in HIV-infected individuals, use of HAART has contributed to a decline in the incidence of non-Hodgkin’s lymphoma (NHL and also a decrease in the overall incidence of ARL. Strategies that employ HAART, improved supportive care, and the use of Rituximab with multi-agent chemotherapy have contributed to improved rates of complete remission and survival of patients with ARL that rival those seen in stage and histology matched HIV negative NHL patients. Most recent clinical trials demonstrate better outcomes with the use of rituximab in ARL. Tumor histogenesis (germinal center vs. non-germinal center origin is associated with lymphoma-specific outcomes in the setting of AIDS-related diffuse-large B cell lymphoma. High-dose chemotherapy (HDCT and autologous stem cell rescue (ASCT can be effective for a subset of patients with relapsed ARL. HIV sero-status alone should not preclude consideration of ASCT in the setting of ARL relapse. Clinical trials investigating the role of allogeneic hematopoietic stem cell transplant in ARL are currently underway.

  18. KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy.

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    Alessandro Soria

    Full Text Available BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR and their ligands class I human leukocyte antigen (HLA, could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+ T-cell count 350/mm(3. Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005. The functional compound genotype HLA-C1(+/KIR2DL3(+, even at multivariable analysis, when adjusted for nadir CD4(+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals 0.34 (0.13-0.88, P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.

  19. Long-term exposure to combination antiretroviral therapy and risk of death from specific causes: no evidence for any previously unidentified increased risk due to antiretroviral therapy

    DEFF Research Database (Denmark)

    Kowalska, Justyna D; Reekie, Joanne; Mocroft, Amanda

    2012-01-01

    were followed from baseline, which was defined as the time of starting cART or enrolment into EuroSIDA whichever occurred later, until death or six months after last follow-up visit. Incidence rates (IR) of death were calculated per 1000 person-years of follow-up (PYFU) and stratified by time...... of exposure to cART (=3 antiretrovirals): 8 years. Duration of cART exposure was the cumulative time actually receiving cART. Poisson regression models were fitted for each cause of death separately. RESULTS:: 1297 patients died during 70613 PYFU (IR 18.3 per 1000 PYFU, 95%CI: 17.4-19.4), 413 due to AIDS (5.......85, 95%CI: 5.28-6.41) and 884 due to non-AIDS-related cause (12.5, 95%CI: 11.7-13.3). After adjustment for confounding variables, including baseline CD4 cell count and HIV RNA, there was a significant decrease in the rate of all-cause and AIDS-related death between 2-3.99 years and longer exposure time...

  20. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-04-01

    Full Text Available Maria João Gomes,1 José das Neves,1,2 Bruno Sarmento1,2 1Instituto de Engenharia Biomédica (INEB, Porto, Portugal; 2Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal Abstract: Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood–brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood–brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. Keywords: HIV/AIDS, blood–brain barrier, protease inhibitors, efflux transporters, drug targeting

  1. Retention of antiretroviral naïve patients registered in HIV care in a program clinic in Pune, India

    Science.gov (United States)

    Ghate, Manisha V.; Zirpe, Sunil S.; Gurav, Nilam P.; Rewari, Bharat B.; Gangakhedkar, Raman R.; Paranjape, Ramesh S.

    2014-01-01

    Background: Retention in HIV care ensures delivery of services like secondary prevention, timely initiation of treatment, support, and care on a regular basis. The data on retention in pre antiretroviral therapy (ART) care in India is scanty. Materials and Methods: Antiretroviral naïve HIV-infected adult patients registered between January 2011 and March 2012 in HIV care (pre-ART) were included in the study. The follow-up procedures were done as per the national guidelines. Patients who did not report to the clinic for 1 year were considered as pre-ART lost to follow-up (pre-ART LFU). They were contacted either telephonically or by home visits. Logistic regression analysis was done to find out factors associated with pre-ART loss to follow-up. Results: A total of 689 antiretroviral naïve adult patients were registered in the HIV care. Fourteen (2%) patients died and 76 (11%) were LFU till March 2013. The multivariate analysis showed that baseline CD4 count >350 cells/mm3 (P ART LFUs, 35 (46.1%) informed that they would visit the clinic at their convenient time. NGOs that referred 16 female sex workers (FSWs) who were LFU (21.1%) informed that they would make efforts to refer them to the clinic. Conclusion: Higher CD4 count and illiteracy were significantly associated with lower retention in pre-ART care. Developing effective “retention package” for patients and strengthening linkage strategies between key sub-population such as FSWs and ART programming will help to plug the leaky cascade in HIV care. PMID:26396447

  2. Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities

    Science.gov (United States)

    Ghislain, Mathilde; Bastard, Jean-Philippe; Meyer, Laurence; Capeau, Jacqueline; Fellahi, Soraya; Gérard, Laurence; May, Thierry; Simon, Anne; Vigouroux, Corinne; Goujard, Cécile

    2015-01-01

    Objectives HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation. Methods Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142). Results Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07). Conclusion After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease. PMID:26636578

  3. Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort.

    Directory of Open Access Journals (Sweden)

    Félix Gutierrez

    Full Text Available BACKGROUND: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. METHODS: Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9% patients died (mortality rate 0.86 per 100 person-years, and 40 (5.3% died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002, and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001. Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. CONCLUSIONS: Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.

  4. 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.

  5. Efek Samping Obat terhadap Kepatuhan Pengobatan Antiretroviral Orang dengan HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Fachri Latif

    2014-12-01

    Full Text Available Tingkat kepatuhan pengobatan antiretroviral di Indonesia sangat rendah, yaitu 40 - 70%, yang masih di bawah target nasional dengan tingkat kepatuhan 95%. Berbeda dengan rata-rata nasional, Puskesmas Jumpandang Baru justru memiliki tingkat kepatuhan pengobatan antiretroviral pasien HIV/AIDS di atas 95%. Penelitian ini bertujuan untuk menganalisis faktor yang paling berpengaruh terhadap kepatuhan pengobatan antiretroviral orang dengan HIV/AIDS (ODHA. Jenis penelitian bersifat observasional analitik dengan pendekatan potong lintang. Populasi penelitian adalah 121 ODHA yang aktif menjalani pengobatan antiretroviral di Puskesmas Jumpandang Baru yang dipilih dengan menggunakan teknik exhaustive sampling. Sampel dalam penelitian ini adalah 121 sampel. Penelitian dilakukan pada 22 April hingga 28 Juni 2014 di klinik Voluntary Counseling and Test Puskesmas Jumpandang Baru Makassar. Analisis data menggunakan uji kai kuadrat dan regresi logistik. Hasil uji kai kuadrat menunjukkan ada hubungan antara pengetahuan, persepsi, riwayat efek samping obat, dukungan keluarga dan teman, serta interaksi antara pasien dengan petugas layanan antiretroviral terhadap kepatuhan pengobatan antiretroviral ODHA. Analisis regresi logistik menunjukan bahwa pengetahuan yang baik, persepsi positif terhadap pengobatan, serta efek samping obat yang tidak dirasakan adalah faktor yang berhubungan dengan kepatuhan pengobatan antiretroviral. Penelitian ini menunjukkan ODHA yang tidak merasakan efek samping obat memiliki kecenderungan terbesar untuk patuh terhadap pengobatan antiretroviral dengan OR sebesar 13,452. Drug Side Effects on Adherence to Antiretroviral Treatment among People Living with HIV/AIDS The rate of adherence to antiretroviral treatment in Indonesia is very low, at 40 - 70%, which is still below our national target (95%. Different phenomena happens at Jumpandang Baru Primary Health Care, whose level of antiretroviral treatment adherence above 95%. This study aimed to

  6. Agreement between physicians and non-physician clinicians in starting antiretroviral therapy in rural Uganda

    Directory of Open Access Journals (Sweden)

    Vasan Ashwin

    2009-08-01

    Full Text Available Abstract Background The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers and physicians in their decisions as to whether to start therapy. Methods We conducted the study at 12 government antiretroviral therapy sites in three regions of Uganda, all of which had staff trained in delivery of antiretroviral therapy using the WHO Integrated Management of Adult and Adolescent Illness guidelines for chronic HIV care. We collected seven key variables to measure patient assessment and the decision as to whether to start antiretroviral therapy, the primary variable of interest being the Final Antiretroviral Therapy Recommendation. Patients saw either a clinical officer or nurse first, and then were screened identically by a blinded physician during the same clinic visit. We measured inter-rater agreement between the decisions of the non-physician health workers and physicians in the antiretroviral therapy assessment variables using simple and weighted Kappa analysis. Results Two hundred fifty-four patients were seen by a nurse and physician, while 267 were seen by a clinical officer and physician. The majority (> 50% in each arm of the study were in World Health Organization Clinical Stages I and II and therefore not currently eligible for antiretroviral therapy according to national antiretroviral therapy guidelines. Nurses and clinical officers both showed moderate to almost perfect agreement with physicians in their Final Antiretroviral Therapy Recommendation (unweighted κ = 0.59 and κ = 0.91, respectively. Agreement was also substantial for nurses versus physicians for assigning World Health Organization Clinical

  7. Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared.

    Directory of Open Access Journals (Sweden)

    Olivia Keiser

    2008-07-01

    Full Text Available The provision of highly active antiretroviral therapy (HAART in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland.We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%. In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%. In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97% in South Africa and 96% (94%-97% in Switzerland, and 26% (22%-29% and 27% (24%-31%, respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2 during months 1-3 and 1.77 (0.90-3.50 during months 4-24.Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are

  8. Pregnancy may be followed by an inflexion of the immune reconstitution in HIV-infected women who receive antiretroviral drugs before conception

    Science.gov (United States)

    Le-Moing, Vincent; Taieb, Audrey; Longuet, Pascale; Lewden, Charlotte; Delcey, Véronique; Drobacheff, Marie Christine; Chêne, Geneviève; Leport, Catherine; the ANRS CO8 (APROCO-COPILOTE) study-group

    2008-01-01

    Summary Background Whether pregnancy has an impact on evolution of CD4+ cell counts in women treated with highly potent antiretrovirals before conception remains largely unknown. Methods Among patients enrolled in the ANRS CO8 (APROCO/COPILOTE) cohort, we selected all women aged between 18 and 50 years at initiation of combination antiretroviral therapy (cART). Slopes of CD4+ cell counts during follow-up were estimated using mixed longitudinal models with time-dependent indicators for pregnancy and delivery. Results Among the 260 selected HIV-infected women, a pregnancy occurred among 39 during a median follow-up of 66 months. Women who became pregnant had higher CD4+ cell count at baseline but this difference was progressively blurred during follow-up because they had a slower increase than women who did not become pregnant. The estimated slope of CD4+ cell count decreased significantly from +2.3 cells/mm3/month before pregnancy and in women who did not become pregnant to − 0.04 cells/mm3/month after delivery (p = 0.0003). Conclusion A significant increase in CD4+ cell count may be preferable before pregnancy in women treated with cART, in order to overcome the evolution observed after pregnancy. PMID:18795961

  9. The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

    Science.gov (United States)

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.

  10. The effect of individual antiretroviral drugs on body composition in HIV-infected persons initiating highly active antiretroviral therapy.

    Science.gov (United States)

    Shlay, Judith C; Sharma, Shweta; Peng, Grace; Gibert, Cynthia L; Grunfeld, Carl

    2009-07-01

    To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ARTs assessed were as follows: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine, and abacavir. Skinfolds and circumferences were measured at baseline and every 4 months. Mid arm, mid thigh, and waist subcutaneous tissue areas and nonsubcutaneous tissue areas were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. d4T and ZDV use was associated with losses in subcutaneous tissue area and skinfold thickness. 3TC use was associated with gains in all subcutaneous tissue areas and skinfold thickness, whereas abacavir use was associated with an increase in waist subcutaneous tissue area. Indinavir was associated with gains in waist subcutaneous tissue area, whereas indinavir, efavirenz, and nevirapine were associated with increases in upper back skinfolds. d4T use was also associated with increases in all nonsubcutaneous tissue areas; 3TC use was associated with the greatest increase in waist nonsubcutaneous tissue area. In this prospective nonrandomized evaluation, the nucleoside reverse transcriptase inhibitors d4T and ZDV were associated with decreases in subcutaneous tissue areas, whereas 3TC use was associated with increased subcutaneous tissue areas and waist nonsubcutaneous tissue area.

  11. Challenges and perspectives of compliance with pediatric antiretroviral therapy in Sub-Saharan Africa.

    Science.gov (United States)

    Dahourou, D L; Leroy, V

    2017-12-01

    More than 3 million children aged less than 15years are infected with HIV worldwide, mainly in Sub-Saharan Africa. The survival of HIV-infected children depends on their access to antiretroviral therapy whose success mainly depends on a good life-long compliance with antiretroviral therapy. Given its complexity and specificity, assessment and monitoring of pediatric compliance with antiretroviral therapy is a major challenge. There is no consensus on a gold standard for monitoring compliance with antiretroviral therapy. Compliance is also influenced by many factors related to the child, the caregiver, the healthcare staff, the healthcare system, and antiretroviral drugs. This review aimed to assess scientific knowledge on pediatric compliance with antiretroviral therapy in Sub-Saharan Africa, and to identify areas for future interventions to improve compliance. Good compliance is essential to achieve the "90% coverage of children on antiretroviral therapy" gold standard of the World Health Organization, and to eliminate HIV infection by 2030. Copyright © 2017. Published by Elsevier SAS.

  12. The prevalence of antiretroviral multidrug resistance in highly active antiretroviral therapy-treated patients with HIV/AIDS between 2004 and 2009 in South Korea.

    Science.gov (United States)

    Choi, Ju-yeon; Kwon, Oh-Kyung; Choi, Byeong-Sun; Kee, Mee-Kyung; Park, Mina; Kim, Sung Soon

    2014-06-01

    Highly active antiretroviral therapy (HAART) including protease inhibitors (PIs) has been used in South Korea since 1997. Currently, more than 20 types of antiretroviral drugs are used in the treatment of human immunodeficiency virus-infected/acquired immune deficiency syndrome patients in South Korea. Despite the rapid development of various antiretroviral drugs, many drug-resistant variants have been reported after initiating HAART, and the efficiency of HAART is limited by these variants. To investigate and estimate the annual antiretroviral drug resistance and prevalence of antiretroviral multi-class drug resistance in Korean patients with experience of treatment. The amplified HIV-1 pol gene in 535 patients requested for genotypic drug resistance testing from 2004 to 2009 by the Korea Centers for Disease Control and Prevention was sequenced and analyzed annually and totally. The prevalence of antiretroviral drug resistance was estimated based on "SIR" interpretation of the Stanford sequence database. Of viruses derived from 787 specimens, 380 samples (48.3%) showed at least one drug class-related resistance. Predicted NRTI drug resistance was highest at 41.9%. NNRTI showed 27.2% resistance with 23.3% for PI. The percent of annual drug resistance showed similar pattern and slightly declined except 2004 and 2005. The prevalence of multi-class drug resistance against each drug class was: NRTI/NNRTI/PI, 9.8%; NRTI/PI, 21.9%; NNRTI/PI, 10.4%; and NRTI/NNRTI, 21.5%. About 50% and less than 10% of patients infected with HIV-1 have multidrug and multiclass resistance linked to 16 antiretroviral drugs, respectively. The significance of this study lies in its larger-scale examination of the prevalence of drug-resistant variants and multidrug resistance in HAART-experienced patients in South Korea. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Impact of combination antiretroviral therapy initiation on adherence to antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Marlene Knight

    2015-10-01

    Full Text Available Background: Healthcare workers are often reluctant to start combination antiretroviral therapy (ART in patients receiving tuberculosis (TB treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects. Object: To quantify changes in adherence to tuberculosis treatment following ART initiation. Design: A prospective observational cohort study of ART-naïve individuals with baseline CD4 count between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by pill count,self-report, and electronic Medication Event Monitoring System (eMEMS before and after initiation of ART. Results: ART tended to negatively affect adherence to TB treatment, with an 8% – 10% decrease in the proportion of patients adherent according to pill count and an 18% – 22% decrease in the proportion of patients adherent according to eMEMS in the first month following ART initiation, independent of the cut-off used to define adherence (90%, 95% or 100%. Reasons for non-adherence were multi factorial, and employment was the only predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence interval 1.06–16.0. Conclusion: Adherence support in the period immediately following ART initiation could optimise treatment outcomes for people living with TB and HIV.

  14. HIV-1 subtypes and response to combination antiretroviral therapy in Europe

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C

    2006-01-01

    Europe/North America on the basis of the most prevalent subtype, B. However, non-B subtypes are increasingly spreading worldwide. OBJECTIVE: To compare virological and immunological response to cART between patients infected with B and non-B subtypes across Europe. DESIGN: EuroSIDA prospective....../ml and immunological response as a CD4+ T-cell count increase of ³100 cells/mm^3. RESULTS: Forty-five percent of patients were antiretroviral naive at initiation of cART. Virological suppression was achieved by 58% of 689 subtype-B-infected patients and 66% of 102 non-B-infected patients (P=0.159). After adjustment...... for potential confounders, there was no significant difference in odds of achieving virological suppression (non-B compared with B; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 0.58-1.93, P=0.866). An immunological response was achieved by 43% of 753 B-infected patients and 48% of 114 non...

  15. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

    Directory of Open Access Journals (Sweden)

    Philip J Palumbo

    Full Text Available Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART. We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM assay was used to analyze baseline (pre-treatment HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008. The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  16. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

    Science.gov (United States)

    Palumbo, Philip J; Wilson, Ethan A; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Kumwenda, Newton; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James G; Hosseinipour, Mina C; Melo, Marineide G; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H; Fogel, Jessica M

    2017-01-01

    Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  17. Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

    Science.gov (United States)

    Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2016-07-01

    Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

  18. Reasons for not starting antiretroviral therapy in HIV-1-infected individuals: a changing landscape.

    Science.gov (United States)

    Fehr, Jan; Nicca, Dunja; Goffard, Jean-Christophe; Haerry, David; Schlag, Michael; Papastamopoulos, Vasileios; Hoepelman, Andy; Skoutelis, Athanasius; Diazaraque, Ruth; Ledergerber, Bruno

    2016-08-01

    A cross-sectional survey was conducted to better understand why chronically HIV-1-infected individuals stratified by CD4 count (≤349; 350-499; ≥500 cells/μL) were not on antiretroviral therapy (ART). Before the consultation, treatment-naive patients and their physicians independently completed a 90-item-questionnaire about barriers and their readiness to start/defer ART. The study was carried out at 34 sites in nine countries in Europe and Australia. Between December 2011 and October 2012, 508 pairs of patient- and physician-questionnaires were completed. 426 (84 %) patients were male and 39 (8 %), 138 (27 %), and 330 (65 %) were in the three stratified groups based on CD4 count, respectively. In the category 'Body and symptoms' the most commonly identified reason for patients not to start was: "As long as I feel good I don't have to take medication" (44 %). Less than 20 % of respondents indicated fears of side effects and toxicity or problems to manage pills. Most patients were in the lowest stage of treatment-readiness (N = 323, 68 %), especially patients with CD4 cells ≥500 cells/μL (N = 240, 79 %). Physicians answered in 92 (18 %) cases that ART was not indicated for CD4 cells perception that patients were 'too depressed' (13 %) or that they had not known them long enough (13 %). Nowadays patient-barriers to ART are commonly related to health-and treatment-beliefs compared to fear of toxicity or ART manageability in the past. This new barrier pattern seems to reflect the era of well tolerated, easier ART regimens and has to be considered in light of the new recommendations to treat all HIV-infected individuals regardless of the CD4 cell count.

  19. Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.

    Science.gov (United States)

    Clarridge, Katherine E; Blazkova, Jana; Einkauf, Kevin; Petrone, Mary; Refsland, Eric W; Justement, J Shawn; Shi, Victoria; Huiting, Erin D; Seamon, Catherine A; Lee, Guinevere Q; Yu, Xu G; Moir, Susan; Sneller, Michael C; Lichterfeld, Mathias; Chun, Tae-Wook

    2018-01-01

    Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals. Here, we show a significant increase of HIV burden in the CD4+ T cells of infected individuals during ATI that was correlated with the level of plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters, including markers of exhaustion and activation, returned to pre-ATI levels 6-12 months after the study participants resumed ART. Of note, the proportions of near full-length, genome-intact and structurally defective HIV proviral DNA sequences were similar prior to ATI and following reinitiation of ART. In addition, there was no evidence of emergence of antiretroviral drug resistance mutations within intact HIV proviral DNA sequences following reinitiation of ART. These data demonstrate that short-term ATI does not necessarily lead to expansion of the persistent HIV reservoir nor irreparable damages to the immune system in the peripheral blood, warranting the inclusion of ATI in future clinical trials evaluating curative strategies.

  20. Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

    Science.gov (United States)

    Werayingyong, Pitsaphun; Phanuphak, Nittaya; Chokephaibulkit, Kulkunya; Tantivess, Sripen; Kullert, Nareeluk; Tosanguan, Kakanang; Butchon, Rukmanee; Voramongkol, Nipunporn; Boonsuk, Sarawut; Pilasant, Songyot; Kulpeng, Wantanee; Teerawattananon, Yot

    2015-03-01

    The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation. © 2013 APJPH.

  1. ADHERENCE TO ANTIRETROVIRAL THERAPY IN A TERTIARY CARE HOSPITAL

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    Muralidhara Panigrahi

    2017-03-01

    Full Text Available BACKGROUND The Million Death Study Collaborators in the British Medical Journal have estimated that the people living with HIV/AIDS population to be between 1.4-1.6 million. Development of Antiretroviral Therapy (ART has been one of the dramatic advances in the history of medicine. Among several factors that can affect the ART outcome, adherence to the ART has been cited as a major factor associated with poor outcomes. For ART to have maximum effect greater than 95%, adherence has been suggested. Additionally, non adherence to ART is a major cause of HIV drug resistance. Especially, in the Indian context, adherence to ART is very important due to the sheer number of HIV/AIDS cases, the socioeconomic status, diversity of the population and regions. That is, the socioeconomic challenges faced by patients contribute to nonadherence to ART in India. With this background, this study was done with the primary objective of assessing the level of adherence to the given regimen of ART as per the NACO guidelines and factors influencing adherence. MATERIALS AND METHODS This is a prospective patient record-based study conducted in the Antiretroviral Therapy Centre at MKCG Medical College, Berhampur, from January 2016 to June 2016. Simple random sampling technique was used to select 150 patients’ records from the ART Centre of the medical college. The data was collected in a predesigned case record form from the patient card available at antiretroviral therapy centre. The patients were followed up through the patient card for six months from their recruitment. The adherence to treatment was evaluated using the adherence score adopted by NACO where a score of 1, 2 and 3 implied that 95%, 80-95% and 95% medication taken. Persons with primary education, married individuals and persons without employment had better improvement in adherence score than other groups. Anaemia was the predominant adverse drug reaction encountered. CONCLUSION The findings of this

  2. Determinants of retention in care in an antiretroviral therapy (ART) program in urban Cameroon, 2003-2005.

    Science.gov (United States)

    Tsague, Landry; Koulla, Sinata S; Kenfak, Alain; Kouanfack, Charles; Tejiokem, Mathurin; Abong, Therese; Mbangue, Madeleine; Mapoure, Yacouba Njankouo; Essomba, Claudine; Mosoko, Jembia; Pouillot, Regis; Menyeng, Louis; Epee, Helene; Tchuani, Carno; Zoung-Kanyi, Anne Cecile; Bella, Lucienne Assumpta; Zekeng, Leopold

    2008-07-04

    Retention in long-term antiretroviral therapy (ART) program remains a major challenge for effective management of HIV infected people in sub-Saharan Africa. Highly Active Antiretroviral Therapy (ART) discontinuation raises concerns about drug resistance and could negate much of the benefit sought by ART programs. Based on existing patient records, we assessed determinants of retention in HIV care among HIV patients enrolled in an urban ART at two urban hospitals in Cameroon. Extended Cox regression procedures were used to identify significant predictors of retention in HIV care. Of 455 patients, 314 (69%) were women, median (IQR) age and baseline CD4 cell count were respectively 36 years (30 - 43) and 110 cells/μL (39 - 177). Forty patients (9%) had active tuberculosis (TB) at enrollment. After a median (IQR) follow-up of 18 months (10-18), 346 (75%) were still in care, 8 (2%) were known dead, and 101 (22%) were lost to follow-up (LFU). Severe immunosuppression (CD4 cell count ≤ 50 cells/μL) at baseline (aHR 2.3; 95% CI 1.4 - 3.7) and active tuberculosis upon enrollment (aHR 1.8; 95% CI 1.0 - 3.6) were independent predictors of cohort losses to follow-up within the first 6 months after HAART initiation. These data suggest that three-quarter of HIV patients initiated on HAART remained in care and on HAART by 18 months; however, those with compromised immunologic status at treatment initiation, and those co-infected with TB were at increased risk for being lost to follow-up within the first 6 months on treatment.

  3. Determinants of survival in adult HIV patients on antiretroviral therapy in Oromiyaa, Ethiopia

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    Andinet Worku Alemu

    2010-10-01

    Full Text Available Background: The antiretroviral treatment (ART scale-up service has been a recent development in Ethiopia, but its impact on mortality has not been well investigated. The aim of this study was to assess the early survival outcome of the scale-up service by utilizing routine hospital data. Methods: All adult HIV/AIDS patients who started on antiretroviral treatment in Shashemene and Assela hospitals from January 1, 2006 to May 31, 2006 were included and followed up for 2 years. Data were extracted from standard patient medical registrations. Kaplan–Meier curves were used to estimate survival probability and the Cox proportional hazard model was applied to determine predictors of mortality. Two alterative assumptions (real case and worst case were made in determining predictors of mortality. Results: The median age of patients was 33 years and 57% were female. Eighty-five percent had CD4 <200 cells/µL with a median CD4 count of 103 cells/µL. The median survival time was 104.4 weeks. A total of 28 (10.3% deaths were observed during the 2-year period and 48 patients (18% were lost to follow up. The majority of deaths occurred in the first 4 months of treatment. In multivariate analysis, 2-year survival was significantly associated with the clinical stage of the disease, baseline hemoglobin, and cotrimoxazole prophylaxis therapy (CPT at or before ART initiation in both assumptions. The median CD4 count and body weight showed a marked improvement during the first 6 months of treatment, followed by stagnation thereafter. Conclusion: The study has shown an overall low mortality but a high loss to follow-up rate of the cohort. Advanced clinical stage, anemia, low body weight, and lack of CPT initiation were independent predictors of mortality – but not gender. CPT initiation should be encouraged in routine HIV care services, and patient retention mechanisms have to be strengthened. Stagnation in immunological and weight recovery after the first 6

  4. Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study.

    Science.gov (United States)

    Dragovic, Gordana; Smith, Colette J; Jevtovic, Djordje; Dimitrijevic, Bozana; Kusic, Jovana; Youle, Mike; Johnson, Margaret A

    2016-03-03

    The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens.

  5. [Policy dilemmas in providing antiretroviral treatment in Brazil].

    Science.gov (United States)

    do Lago, Regina Ferro; Costa, Nilson do Rosário

    2010-11-01

    This paper addresses institutional constraints that have affected Brazilian politics regarding provision of anti-retroviral treatment (ART) to HIV/Aids patients. We analyzed the normative conflict resulting from international agreements on intellectual property rights, especially patent protection, and the constitutional rights of Brazilian patients to universal and free access to ART. These constraints have not substantially changed the Brazilian public policy yet, but they may impact the future sustainability of this policy. As the main barrier to the production of patented drugs is not technological but institutional, Brazilian government faces a dilemma. It may either abide by existing monopolistic restrictions or it may incite competitiveness of domestic industries and developing countries in the pharmaceutical market.

  6. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu

    2016-01-01

    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  7. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

    Directory of Open Access Journals (Sweden)

    Kimberly N. Capers

    2011-01-01

    Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

  8. What Time is it? Adherence to Antiretroviral Therapy in Ethiopia.

    Science.gov (United States)

    Tiruneh, Yordanos M; Wilson, Ira B

    2016-11-01

    This study assessed adherence to antiretroviral therapy (ART) among people living with HIV/AIDS in Ethiopia and explored the sociocultural context in which they relate to their regimen requirements. Data were collected through semi-structured in-depth interviews with 105 patients on ART and observations held at the study clinic. We analyzed data using both qualitative and quantitative methods. Our findings indicate that study participants are highly adherent to dose but less adherent to dose schedule. Strict dose time instructions were reported as stressful and unrealistic. The discrepancy between adherence to dose and dose schedule could be explained by time perception, difficulty with the strictness of medication regimens, or beliefs about dose timing adherence. Care providers should acknowledge the complexities of medication practices and engage in shared decision-making to incorporate patients' perspectives and identify effective interventions.

  9. Platelet count kinetics following interruption of antiretroviral treatment.

    Science.gov (United States)

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V; Somboonwit, Charurut; Llibre, Josep M; Palfreeman, Adrian; Chini, Maria; Lundgren, Jens D

    2013-01-02

    To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. SMART patients from sites that determined platelets routinely. Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/μl (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels. Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.

  10. Use of Third Line Antiretroviral Therapy in Latin America

    Science.gov (United States)

    Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

    2014-01-01

    Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931

  11. [Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams].

    Science.gov (United States)

    Yokaichiya, Chizuru Minami; Figueiredo, Wagner dos Santos; Schraiber, Lilia Blima

    2007-12-01

    To understand the perceptions of pharmacy teams about their role in the healthcare assistance challenges and adherence to antiretroviral therapy by injecting drug users living with HIV/AIDS. Qualitative study through focus groups and thematic discourse analysis of pharmacists, technicians and assistants with more than six months of experience with medication supply, in 15 assisting units for STD/AIDS in the city of São Paulo, in 2002. Three groups were formed, totaling 29 participants, originating from 12 out of the 15 existing services, and including 12 university level professionals and 17 high-school level professionals. The groups concluded that the pharmacy has an important role in the antiretroviral drug supply, which is reflected in the treatment adherence, because trust-based relationships can be built up through their procedures. In spite of this, they pointed out that such building-up does not take place through excessively bureaucratic activities. This has negative repercussions for all patients, especially for injecting drug users, considered "difficult people". Such concept sums up their behavior: they are supposed to be confused and incapable to adhere to treatment, and have limited understanding. Staff members, however, affirm they treat these patients equally. They do not realize that, by this acting, the specific needs of injecting drug users may become invisible in the service. There is also the possibility that stigmatizing stereotypes may be created, resulting in yet another barrier to the work on adherence. Although the pharmacy is recommended as a potentially favorable place to listen to and form bonds with users, the results show objective and subjective obstacles to render it suitable for the work on adherence.

  12. Use of third line antiretroviral therapy in Latin America.

    Directory of Open Access Journals (Sweden)

    Carina Cesar

    Full Text Available Access to highly active antiretroviral therapy (HAART is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known.Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART.Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3% failed a second line regimen and 44 (0.8% received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18-2.00, p = 0.001, younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86-4.10, p<0.001, and prior AIDS (HR = 2.17, 95% CI 1.62-2.90, p<0.001.Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.

  13. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

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    Benjamin B Policicchio

    2016-09-01

    Full Text Available Viruses that persist despite seemingly effective antiretroviral treatment (ART and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control

  14. Gaps in the Implementation of Anti-Retroviral Treatment: A Case for ...

    African Journals Online (AJOL)

    ... of Anti-Retroviral Treatment: A Case for Addressing Gender and Mental Health ... to score successes in ensuring adherence to ART as well as reducing new HIV ... lack of established clinical infrastructure, negative social stigma and the cost ...

  15. Use of non-antiretroviral drugs among individuals with and without HIV-infection

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Kronborg, Gitte; Larsen, Carsten S

    2017-01-01

    AIM: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population. METHODS: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported...... no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non-antiretroviral drugs. Data were analyzed according...... to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes. RESULTS: We identified 4,928 HIV-infected individuals (median...

  16. Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

    NARCIS (Netherlands)

    Ananworanich, Jintanat; Melvin, Diane; Amador, Jose T. R.; Childs, Tristan; Medin, Gabriela; Boscolo, Valentina; Compagnucci, Alexandra; Kanjanavanit, Suparat; Montero, Samuel; Gibb, Diana M.; Aboulker, J. -P.; Babiker, A.; Belfrage, E.; Bernardi, S.; Bologna, R.; Burger, D.; Butler, K.; Castelli-Gattinara, G.; Castro, H.; Clayden, P.; Compagnucci, A.; Cressey, T.; Darbyshire, J. H.; Debré, M.; de Groot, R.; della Negra, M.; Di Biagio, A.; de Rossi, A.; Duicelescu, D.; Faye, A.; Giaquinto, C.; Giacomet, V.; Gibb, D. M.; Grosch-Wörner, I.; Hainault, M.; Klein, N.; Lallemant, M.; Levy, J.; Lyall, H.; Marczynska, M.; Marques, L.; Mardarescu, M.; Mellado Peña, M. J.; Nadal, D.; Nastouli, E.; Naver, L.; Niehues, T.; Peckham, C.; Pillay, D.; Popieska, J.; Ramos Amador, J. T.; Rojo Conejo, P.; Rosado, L.; Rosso, R.; Rudin, C.; Scherpbier, H. J.; Sharland, M.; Stevanovic, M.; Thorne, C.; Tovo, P. A.; Tudor-Williams, G.; Turkova, A.; Valerius, N.; Volokha, A.; Walker, A. S.; Welch, S.; Wintergerst, U.; Aboulker, J. P.; Burger, D. M.; Green, H.; Harper, L.; Mofenson, L.; Moye, J.; Saïdi, Y.; Cressey, T. R.; Jacqz-Aigrain, E.; Khoo, S.; Regazzi, M.; Tréluyer, J. M.; Ngo-Giang-Huong, N.; Muñoz Fernandez, M. A.; Hill, C.; Lepage, P.; Pozniak, A.; Vella, S.; Chêne, G.; Vesikari, T.; Hadjou, G.; Léonardo, S.; Riault, Y.; Bleier, J.; Buck, L.; Duong, T.; Farrelly, L.; Forcat, S.; Harrison, L.; Horton, J.; Johnson, D.; Montero, S.; Taylor, C.; Chalermpantmetagul, S.; Peongjakta, R.; Khamjakkaew, W.; Than-in-at, K.; Chailert, S.; Jourdain, G.; Le Coeur, S.; Floret, D.; Costanzo, P.; Le Thi, T. T.; Monpoux, F.; Mellul, S.; Caranta, I.; Boudjoudi, N.; Firtion, G.; Denon, M.; Charlemaine, E.; Picard, F.; Hellier, E.; Heuninck, C.; Damond, F.; Alexandre, G.; Tricoire, J.; Antras, M.; Lachendowier, C.; Nicot, F.; Krivine, A.; Rivaux, D.; Notheis, G.; Strotmann, G.; Schlieben, S.; Rampon, O.; Boscolo, V.; Zanchetta, M.; Ginocchio, F.; Viscoli, C.; Martino, A.; Pontrelli, G.; Baldassar, S.; Concato, C.; Mazza, A.; Rossetti, G.; Dobosz, S.; Oldakowska, A.; Popielska, J.; Kaflik, M.; Stanczak, J.; Stanczack, G.; Dyda, T.; Kruk, M.; González Tomé, M. I.; Delgado García, R.; Fernandez Gonzalez, M. T.; Medin, G.; Mellado Peña, M. José; Martín Fontelos, P.; Garcia Mellado, M. I.; Medina, A. F.; Ascencion, B.; Garcia Bermejo, I.; Navarro Gomez, D. M. L.; Saavedra, J.; Prieto, C.; Jimenez, J. L.; Muñoz-Fernandez, M. A.; Garcia Torre, A.; de José Gómez, M. I.; García Rodriguez, M. C.; Moreno Pérez, D.; Núñez Cuadros, E.; Asensi-Botet, F.; Otero Reigada, C.; Pérez Tamarit, M. D.; Vilalta, R.; Molina Moreno, J. M.; Rainer, Truninger; Schupbach, J.; Rutishauser, M.; Bunupuradah, T.; Butterworth, O.; Phasomsap, C.; Prasitsuebsai, W.; Chuanjaroen, T.; Jupimai, T.; Ubolyam, S.; Phanuphak, P.; Puthanakit, T.; Pancharoen, C.; Mai, Chaing; Kanjanavanit, S.; Namwong, T.; Punsakoon, W.; Payakachat, S.; Chutima, D.; Raksasang, M.; Foster, C.; Hamadache, D.; Campbell, S.; Newbould, C.; Monrose, C.; Abdulla, A.; Walley, A.; Melvin, D.; Patel, D.; Kaye, S.; Seery, P.; Rankin, A.; Wildfire, A.; Novelli, V.; Shingadia, D.; Moshal, K.; Flynn, J.; Clapson, M.; Allen, A.; Spencer, L.; Rackstraw, C.; Ward, B.; Parkes, K.; Depala, M.; Jacobsen, M.; Poulsom, H.; Barkley, L.; Miah, J.; Lurie, P.; Keane, C.; McMaster, P.; Phipps, M.; Orendi, J.; Farmer, C.; Liebeschuetz, S.; Sodeinde, O.; Wong, S.; Bostock, V.; Heath, Y.; Scott, S.; Gandhi, K.; Lewis, P.; Daglish, J.; Miles, K.; Summerhill, L.; Subramaniam, B.; Weiner, L.; Famiglietti, M.; Rana, S.; Yu, P.; Roa, J.; Puga, A.; Haerry, A.

    2016-01-01

    Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n =

  17. RESEARCH Recall of lost-to-follow-up pre-antiretroviral therapy ...

    African Journals Online (AJOL)

    trained in nurse initiation and maintenance of antiretroviral therapy. (NIMART). .... of this project. Good relationships were initially established, current ... mentor travel and accommodation costs were provided by the President's. Emergency ...

  18. Determinants of antiretroviral therapy adherence in northern Tanzania: a comprehensive picture from the patient perspective

    NARCIS (Netherlands)

    Lyimo, R.A.; de Bruin, M.; Boogaard, J. van den; Hospers, H.J.; Ven, A. van der; Mushi, D.

    2012-01-01

    ABSTRACT: BACKGROUND: To design effective, tailored interventions to support antiretroviral therapy (ART) adherence, a thorough understanding of the barriers and facilitators of ART adherence is required. Factors at the individual and interpersonal level, ART treatment characteristics and health

  19. Determinants of antiretroviral therapy adherence in northern Tanzania: a comprehensive picture from the patient perspective

    NARCIS (Netherlands)

    Lyimo, R.A.; Bruin, de M.; Boogaard, van den J.; Hospers, H.J.; Ven, van der A.; Mushi, D.

    2012-01-01

    Background - To design effective, tailored interventions to support antiretroviral therapy (ART) adherence, a thorough understanding of the barriers and facilitators of ART adherence is required. Factors at the individual and interpersonal level, ART treatment characteristics and health care factors

  20. Determinants of antiretroviral therapy adherence in northern Tanzania: a comprehensive picture from the patient perspective

    NARCIS (Netherlands)

    Lyimo, R.A.; de Bruin, M.; van den Boogaard, J.; Hospers, H.J.; van der Ven, A.; Mushi, D.

    2012-01-01

    Background To design effective, tailored interventions to support antiretroviral therapy (ART) adherence, a thorough understanding of the barriers and facilitators of ART adherence is required. Factors at the individual and interpersonal level, ART treatment characteristics and health care factors

  1. Pregnancy Outcome of HIV-Infected Women on Anti-Retroviral ...

    African Journals Online (AJOL)

    User

    antiretroviral treatment (ARVs) to HIV-positive pregnant women. The aim of this ..... possible should be considered a vital means of reducing the maternal mortality and other adverse maternal .... load suppression, and pregnancy outcomes.

  2. Delays by people living with HIV/AIDS in accessing antiretroviral ...

    African Journals Online (AJOL)

    Objective: To understand, by qualitative enquiry, the underlying reasons and narratives ... denial, practical clinic constraints and appropriate types of health education. Keywords: qualitative research, delays, access, antiretroviral drugs, ARVs ...

  3. Concomitant medication polypharmacy, interactions and imperfect adherence are common in Australian adults on suppressive antiretroviral therapy

    NARCIS (Netherlands)

    Siefried, Krista J; Mao, Limin; Cysique, Lucette A; Rule, John; Giles, Michelle L; Smith, Don E; McMahon, James E.; Read, Tim R; Ooi, Catriona; Tee, Ban K; Bloch, Mark; de Wit, John; Carr, Andrew

    2018-01-01

    OBJECTIVES: We quantified concomitant medication polypharmacy, pharmacokinetic and pharmacodynamic interactions, adverse effects and adherence in Australian adults on effective antiretroviral therapy. DESIGN: Cross-sectional. METHODS: Patients recruited into a nationwide cohort and assessed for

  4. Gender Barriers to Access to Antiretroviral Therapy and its Link to ...

    African Journals Online (AJOL)

    Gender Barriers to Access to Antiretroviral Therapy and its Link to ... to assess executive function, verbal fluency, working memory, learning memory, recall, ... there were no gender differences in performance in the neuropsychological testing.

  5. Population-based CD4 counts in a rural area in South Africa with high HIV prevalence and high antiretroviral treatment coverage.

    Directory of Open Access Journals (Sweden)

    Abraham Malaza

    Full Text Available Little is known about the variability of CD4 counts in the general population of sub-Saharan Africa countries affected by the HIV epidemic. We investigated factors associated with CD4 counts in a rural area in South Africa with high HIV prevalence and high antiretroviral treatment (ART coverage.CD4 counts, health status, body mass index (BMI, demographic characteristics and HIV status were assessed in 4990 adult resident participants of a demographic surveillance in rural KwaZulu-Natal in South Africa; antiretroviral treatment duration was obtained from a linked clinical database. Multivariable regression analysis, overall and stratified by HIV status, was performed with CD4 count levels as outcome.Median CD4 counts were significantly higher in women than in men overall (714 vs. 630 cells/µl, p<0.0001, both in HIV-uninfected (833 vs. 683 cells/µl, p<0.0001 and HIV-infected adults (384.5 vs. 333 cells/µl, p<0.0001. In multivariable regression analysis, women had 19.4% (95% confidence interval (CI 16.1-22.9 higher CD4 counts than men, controlling for age, HIV status, urban/rural residence, household wealth, education, BMI, self-reported tuberculosis, high blood pressure, other chronic illnesses and sample processing delay. At ART initiation, HIV-infected adults had 21.7% (95% CI 14.6-28.2 lower CD4 counts than treatment-naive individuals; CD4 counts were estimated to increase by 9.2% (95% CI 6.2-12.4 per year of treatment.CD4 counts are primarily determined by sex in HIV-uninfected adults, and by sex, age and duration of antiretroviral treatment in HIV-infected adults. Lower CD4 counts at ART initiation in men could be a consequence of lower CD4 cell counts before HIV acquisition.

  6. Improved quality of life with immediate versus deferred initiation of antiretroviral therapy in early asymptomatic HIV infection.

    Science.gov (United States)

    Lifson, Alan R; Grund, Birgit; Gardner, Edward M; Kaplan, Richard; Denning, Eileen; Engen, Nicole; Carey, Catherine L; Chen, Fabian; Dao, Sounkalo; Florence, Eric; Sanz, Jesus; Emery, Sean

    2017-04-24

    To determine if immediate compared to deferred initiation of antiretroviral therapy (ART) in healthy persons living with HIV had a more favorable impact on health-related quality of life (QOL), or self-assessed physical, mental, and overall health status. QOL was measured in the Strategic Timing of Antiretroviral Therapy study, which randomized healthy ART-naive persons living with HIV with CD4 cell counts above 500 cells/μl from 35 countries to immediate versus deferred ART. At baseline, months 4 and 12, then annually, participants completed a visual analog scale (VAS) for 'perceived current health' and the Short-Form 12-Item Health Survey version 2 from which the following were computed: general health perception; physical component summary (PCS); and mental component summary (MCS); the VAS and general health were rated from 0 (lowest) to 100 (highest). QOL at study entry was high (mean scores: VAS = 80.9, general health = 72.5, PCS = 53.7, MCS = 48.2). Over a mean follow-up of 3 years, changes in all QOL measures favored the immediate group (P < 0.001); estimated differences were as follows: VAS = 1.9, general health = 3.6, PCS = 0.8, MCS = 0.9. When QOL changes were assessed across various demographic and clinical subgroups, treatment differences continued to favor the immediate group. QOL was poorer in those experiencing primary outcomes; however, when excluding those with primary events, results remained favorable for immediate ART recipients. In an international randomized trial in ART-naive participants with above 500 CD4 cells/μl, there were modest but significant improvements in self-assessed QOL among those initiating ART immediately compared to deferring treatment, supporting patient-perceived health benefits of initiating ART as soon as possible after an HIV diagnosis.

  7. Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.

    Science.gov (United States)

    Sperk, Maike; Zhang, Wang; Nowak, Piotr; Neogi, Ujjwal

    2018-02-01

    Acute human immunodeficiency virus (HIV) infection is associated with a marked induction of several pathways that are linked to inflammation and CD4 T-cell depletion. Many of these processes do not fully resolve on short-term combination antiretroviral therapy (cART) (15 years) successful antiretroviral therapy (ART) and the linkage between levels of biomarkers remain unclear. Therefore, the present study aims to assess the host plasma proteome in a well-defined clinical material from HIV-1-positive male patients on successful long-term ART (>15 years) and compared them with age-matched healthy controls and treatment-naïve male patients with viremia in a cross-sectional manner.Plasma samples were obtained from 3 categories of age-matched HIV-1-positive male patients on long-term successfully (ART, n = 10) with a median (Interquartile range, IQR) of 19 (17-20) years, treatment-naïve patients with viremia (VP, n = 14), and HIV-1-negative persons (HC, n = 11). Plasma proteome was analyzed using the proximity extension assay targeting 92 factors. Statistical analyses were performed with GraphPad Prism v7, R-packages, and Qlucore Omics Explorer v3.2. Functional enrichment analysis was performed by Kyoto Encyclopedia of Genes and Genomes (KEGG), and interactions of specific molecules were identified using Path Designer integrated into Ingenuity Pathway Analysis (IPA).Group wise comparison identified 53 soluble factors, which differed between the groups (P studied groups (adjusted P HIV-negative individuals despite successful long-term ART. Additional analysis of NK cells along with T-cell subsets can provide insights into the long-term effects of ART on the immune system.

  8. Prescribing and using self-injectable antiretrovirals: How concordant are physician and patient perspectives?

    OpenAIRE

    Cohen Calvin; Fisher Martin; Youle Michael; Kulasegaram Ranjababu; Fumaz Carmina R; Clotet Bonaventura; Katlama Christine; Kovacs Colin; Horne Robert; Slim Jihad; Shalit Peter; Cooper Vanessa; Tsoukas Christos

    2009-01-01

    Abstract Background The selection of agents for any treatment regimen is in part influenced by physician and patient attitudes. This study investigated attitudinal motivators and barriers to the use of self-injectable antiretroviral agents among physicians and patients and measured the degree of concordance between physician and patient perspectives. Methods Attitudes toward prescribing and usage of self-injectable antiretroviral therapy (SIAT) were assessed by structured interview in 2 cohor...

  9. Quality of life of people living with HIV and AIDS and antiretroviral therapy

    OpenAIRE

    Oguntibeju, Oluwafemi

    2012-01-01

    Oluwafemi O OguntibejuOxidative Stress Research Centre, Cape Peninsula University of Technology, Bellville, South AfricaAbstract: The development of antiretroviral drugs has significantly changed the perception of HIV/AIDS from a very fatal to a chronic and potentially manageable disease, and the availability and administration of antiretroviral therapy (ART) has significantly reduced mortality and morbidity associated with HIV and AIDS. There is a relationship between ART and quality of life...

  10. Self-reported adverse reactions among patients initiating antiretroviral therapy in Brazil

    OpenAIRE

    Pádua,Cristiane A. Menezes de; César,Cibele C.; Bonolo,Palmira F.; Acurcio,Francisco A.; Guimarães,Mark Drew C.

    2007-01-01

    A cross-sectional analysis was carried out to describe adverse reactions to antiretroviral therapy (ART) reported by HIV-infected patients initiating treatment at two public health AIDS referral centers in Belo Horizonte, Brazil, 2001-2003 and to verify their association with selected variables. Adverse reactions were obtained through interview at the first follow-up visit (first month) after the antiretroviral prescription. Socio-demographic and behavioral variables related to ART were obtai...

  11. Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Walter de Araujo Eyer-Silva

    2012-08-01

    Full Text Available Immune reconstitution inflammatory syndrome (IRIS in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

  12. Antiretroviral therapy, immune suppression and renal impairment in HIV-positive persons

    DEFF Research Database (Denmark)

    Nielsen, Lene Ryom; Mocroft, Amanda; Lundgren, Jens D

    2014-01-01

    The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field.......The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field....

  13. A Systematic Review of Antiretroviral Adherence Interventions for HIV-Infected People Who Use Drugs

    OpenAIRE

    CampBinford, Meredith; Kahana, Shoshana Y.; Altice, Frederick L.

    2012-01-01

    HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of interventions to improve cART adherence and virologic outcomes among HIV-infected PWUDs was conducted. Among the 45 eligible studies, randomized controlled trials suggested directly administered antiretroviral therapy, medication-assisted therapy (MAT), contingency management, and multi-component, nurse-delivered interventions provid...

  14. Outcomes in a cohort of women who discontinued maternal triple-antiretroviral regimens initially used to prevent mother-to-child transmission during pregnancy and breastfeeding--Kenya, 2003-2009.

    Directory of Open Access Journals (Sweden)

    Timothy D Minniear

    Full Text Available In 2012, the World Health Organization (WHO amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT (Option B to include the option to continue lifelong combination antiretroviral therapy (cART (Option B+. We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum.The Kisumu Breastfeeding Study, 2003-2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naïve, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4 <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning-when tARV-PMTCT discontinued-by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P = 0.03. Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4-40.6 or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9-5.0 were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing.Considering the serious health risks to the woman's infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at

  15. Otitis media in Brazilian human immunodeficiency virus infected children undergoing antiretroviral therapy.

    Science.gov (United States)

    Miziara, I D; Weber, R; Araújo Filho, B Cunha; Pinheiro Neto, C Diógenes

    2007-11-01

    To assess changes in the prevalence of otitis media, associated with the use of highly active antiretroviral therapy, in Brazilian human immunodeficiency virus (HIV) infected children. Division of otorhinolaryngology, Hospital das Clínicas, Sao Paulo University Medical School, Brazil. A cohort of 459 HIV-infected children aged below 13 years. The prevalence of otitis media and the serum cluster of differentiation four glycoprotein T lymphocyte count were compared for children receiving highly active antiretroviral therapy (with protease inhibitors) and those receiving standard antiretroviral therapy (without protease inhibitors). Otitis media was present in 33.1 per cent of the children. Children aged from zero years to five years 11 months receiving highly active antiretroviral therapy had a higher prevalence of acute otitis media (p=0.02) and a lower prevalence of chronic otitis media (p=0.02). Children who were receiving highly active antiretroviral therapy had a mean serum cluster of differentiation four glycoprotein T lymphocyte count greater than that of those who were receiving standard antiretroviral therapy (pBrazilian HIV-infected children was associated with a lower prevalence of chronic otitis media.

  16. Low-Cost Method to Monitor Patient Adherence to HIV Antiretroviral Therapy Using Multiplex Cathepsin Zymography.

    Science.gov (United States)

    Platt, Manu O; Evans, Denise; Keegan, Philip M; McNamara, Lynne; Parker, Ivana K; Roberts, LaDeidra M; Caulk, Alexander W; Gleason, Rudolph L; Seifu, Daniel; Amogne, Wondwossen; Penny, Clement

    2016-01-01

    Monitoring patient adherence to HIV antiretroviral therapy (ART) by patient survey is inherently error prone, justifying a need for objective, biological measures affordable in low-resource settings where HIV/AIDS epidemic is highest. In preliminary studies conducted in Ethiopia and South Africa, we observed loss of cysteine cathepsin activity in peripheral blood mononuclear cells of HIV-positive patients on ART. We optimized a rapid protocol for multiplex cathepsin zymography to quantify cysteine cathepsins, and prospectively enrolled 350 HIV-positive, ART-naïve adults attending the Themba Lethu Clinic, Johannesburg, South Africa, to test if suppressed cathepsin activity could be a biomarker of ART adherence (103 patients were included in final analysis). Poor adherence was defined as detectable viral load (>400 copies/ml) or simplified medication adherence questionnaire, 4-6 months after ART initiation. 86 % of patients with undetectable viral loads after 6 months were cathepsin negative, and cathepsin-positive patients were twice as likely to have detectable viral loads (RR 2.32 95 % CI 1.26-4.29). Together, this demonstrates proof of concept that multiplex cathepsin zymography may be an inexpensive, objective method to monitor patient adherence to ART. Low cost of this electrophoresis-based assay makes it a prime candidate for implementation in resource-limited settings.

  17. Low cost method to monitor patient adherence to HIV antiretroviral therapy using multiplex cathepsin zymography

    Science.gov (United States)

    Platt, Manu O.; Evans, Denise; Keegan, Philip M.; McNamara, Lynne; Parker, Ivana K.; Roberts, LaDeidra M.; Caulk, Alexander W.; Gleason, Rudolph L.; Seifu, Daniel; Amogne, Wondwossen; Penny, Clement

    2015-01-01

    Monitoring patient adherence to HIV antiretroviral therapy (ART) by patient survey is inherently error-prone, justifying a need for objective, biological measures affordable in low resource settings where HIV/AIDS epidemic is highest. In preliminary studies conducted in Ethiopia and South Africa, we observed loss of cysteine cathepsin activity in peripheral blood mononuclear cells (PBMCs) of HIV-positive patients on ART. We optimized a rapid protocol for multiplex cathepsin zymography to quantify cysteine cathepsins, and prospectively enrolled 350 HIV-positive, ART naïve adults attending the Themba Lethu Clinic, Johannesburg, South Africa, to test if suppressed cathepsin activity could be a biomarker of ART adherence (103 patients were included in final analysis). Poor adherence was defined as detectable viral load (>400 copies/ml) or simplified medication adherence questionnaire (SMAQ), 4–6 months after ART initiation. 86% of patients with undetectable viral loads after 6 months were cathepsin negative, and cathepsin positive patients were twice as likely to have detectable viral loads (RR 2.32 95% CI 1.26–4.29). Together, this demonstrates proof of concept that multiplex cathepsin zymography may be an inexpensive, objective method to monitor patient adherence to ART. Low cost of this electrophoresis based assay makes it a prime candidate for implementation in resource limited settings. PMID:26589706

  18. Experiences and perceptions of patients with 100% adherence to highly active antiretroviral therapy: a qualitative study.

    Science.gov (United States)

    Sidat, Mohsin; Fairley, Christopher; Grierson, Jeffrey

    2007-07-01

    A decade has passed since the introduction of highly active antiretroviral therapy (HAART) as standard of care for HIV/AIDS patients. The success of HAART is largely dependent on almost 100% adherence to it. In this study our primary aim was to understand from patients' own perspectives and experiences what resulted in them having 100% adherence to HAART. Thus, we purposefully recruited for in-depth interviews 10 participants (7 men and 3 women) with 100% adherence to HAART (>/=6 months previous to the interviews). All interviews were transcribed verbatim and analyzed by using Giorgi's phenomenological analysis approach. The following issues emerged from the analysis: readiness to go on HAART; HAART viewed as a life-line; maintenance of 100% adherence related with willingness to live longer and healthier; optimal ongoing patient-physician relationship, better coping and/or lack of perceived side effects; and improvements in clinical condition as well as in CD4 T-cells count and viral load reinforced the motivation to continue 100% adherence. The study findings should be helpful for health professionals caring for HIV-infected individuals on HAART.

  19. Early severe morbidity and resource utilization in South African adults on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Meintjes Graeme A

    2009-12-01

    Full Text Available Abstract Background High rates of mortality and morbidity have been described in sub-Saharan African patients within the first few months of starting highly active antiretroviral therapy (HAART. There is limited data on the causes of early morbidity on HAART and the associated resource utilization. Methods A cross-sectional study was conducted of medical admissions at a secondary-level hospital in Cape Town, South Africa. Patients on HAART were identified from a register and HIV-infected patients not on HAART were matched by gender, month of admission, and age group to correspond with the first admission of each case. Primary reasons for admission were determined by chart review. Direct health care costs were determined from the provider's perspective. Results There were 53 in the HAART group with 70 admissions and 53 in the no-HAART group with 60 admissions. The median duration of HAART was 1 month (interquartile range 1-3 months. Median baseline CD4 count in the HAART group was 57 × 106 cells/L (IQR 15-115. The primary reasons for admission in the HAART group were more likely to be due to adverse drug reactions and less likely to be due to AIDS events than the no-HAART group (34% versus 7%; p Conclusions Causes of early morbidity are different and more complex in HIV-infected patients on HAART. This results in greater resource utilization of diagnostic and therapeutic services.

  20. Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

    Science.gov (United States)

    Paton, Nicholas I.; Goodall, Ruth L.; Dunn, David T.; Franzen, Samuel; Collaco-Moraes, Yolanda; Gazzard, Brian G.; Williams, Ian G.; Fisher, Martin J.; Winston, Alan; Fox, Julie; Orkin, Chloe; Herieka, Elbushra A.; Ainsworth, Jonathan G.; Post, Frank A.; Wansbrough-Jones, Mark; Kelleher, Peter

    2013-01-01

    Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in

  1. Potential drug interactions in patients given antiretroviral therapy.

    Science.gov (United States)

    Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

    2016-11-21

    to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. investigar potenciais interações droga-droga (PDDI) em pacientes infectados com HIV em terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral. Houve uma associação entre o uso de cinco ou mais medicamentos e possíveis interações droga-droga (p = 0.000), e entre o período de tempo de terapia antirretroviral acima de seis anos e possíveis interações droga

  2. Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

    Science.gov (United States)

    Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

  3. Quality of life outcomes of antiretroviral treatment for HIV/AIDS patients in Vietnam.

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    Bach Xuan Tran

    Full Text Available OBJECTIVE: This study assessed health-related quality of life (HRQOL and its related factors in HIV/AIDS patients taking antiretroviral treatment (ART in Vietnam. METHODS: A cross-sectional study was conducted with 1016 patients (36.2% women, mean age = 35.4 in three epicenters of Vietnam, including Hanoi, Hai Phong, and Ho Chi Minh City. HRQOL was assessed using the Vietnamese version of the WHOQOL-HIV BREF. Factor analysis classified measure items into six HRQOL dimensions, namely Physical, Morbidity, Social, Spirituality, Performance, and Environment. Tobit censored regression models were applied to determine associations of patient's characteristics and HRQOL domain scores. RESULTS: Internal consistency reliability of the six domains ranged from 0.69 to 0.89. The WHOQOL-HIV BREF had a good discriminative validity with patient's disease stages, CD4 cell counts, and duration of ART. In a band score of (4, 20, six domains were moderate; "Environment" had the highest score (13.8±2.8, and "Social" had the lowest score (11.2±3.3. Worse HRQOL were observed in patients at provincial and district clinics. Those patients who were male, had higher educational attainment, and are employed, reported better HRQOL. In reduced regression models, poorer HRQOL was found in patients who had advanced HIV infection and had CD4 cell count <200 cells/mL. Patients reported significantly poorer Physical and Social in the 1(st year ART, but moderately better Performance, Morbidity, Spirituality, and Environment from the 2(nd year ART, compared to those not-yet-on ART. CONCLUSION: Strengthening the quality of ART services at the provincial and district levels, gender-specific impact mitigation, and early treatment supports are recommended for further expansion of ART services in Vietnam. Regular assessments of HRQOL may provide important indicators for monitoring and evaluating HIV/AIDS services.

  4. The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV) Genome Load in HIV-Infected Patients

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    Friis, Anna M. C.; Gyllensten, Katarina; Aleman, Anna; Ernberg, Ingemar; Åkerlund, Börje

    2010-01-01

    We evaluated the effect of combination anti-retroviral treatment (cART) on the host control of EBV infection in moderately immunosuppressed HIV-1 patients. Twenty HIV-1 infected individuals were followed for five years with repeated measurements of EBV DNA load in peripheral blood lymphocytes in relation to HIV-RNA titers and CD4+ cell counts. Individuals with optimal response, i.e. durable non-detectable HIV-RNA, showed a decline of EBV load to the level of healthy controls. Individuals with non-optimal HIV-1 control did not restore their EBV control. Long-lasting suppression of HIV-replication after early initiation of cART is a prerequisite for re-establishing the immune control of EBV. PMID:21994658

  5. The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV Genome Load in HIV-Infected Patients

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    Anna M. C. Friis

    2010-03-01

    Full Text Available We evaluated the effect of combination anti-retroviral treatment (cART on the host control of EBV infection in moderately immunosuppressed HIV-1 patients. Twenty HIV-1 infected individuals were followed for five years with repeated measurements of EBV DNA load in peripheral blood lymphocytes in relation to HIV-RNA titers and CD4+ cell counts. Individuals with optimal response, i.e. durable non-detectable HIV-RNA, showed a decline of EBV load to the level of healthy controls. Individuals with non-optimal HIV-1 control did not restore their EBV control. Long-lasting suppression of HIV-replication after early initiation of cART is a prerequisite for re-establishing the immune control of EBV.

  6. Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era

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    Touma, Madeleine; Rasmussen, Line D.; Martin-Iguacel, Raquel

    2017-01-01

    Background: Human immunodeficiency virus (HIV) infection with advanced immunosup-pression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era. Methods......: A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995–2014 was included in this study. Results: Among 6,351 HIV...... was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00–4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4 + cell count

  7. Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era

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    Touma, Madeleine; Rasmussen, Line D.; Martin-Iguacel, Raquel

    2017-01-01

    : A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995-2014 was included in this study. RESULTS: Among 6,351 HIV......BACKGROUND: Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era. METHODS...... was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00-4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4(+) cell count

  8. Efficacy of Prompt Initiation of Antiretroviral Therapy in the Treatment of Hemophagocytic Lymphohistiocytosis Triggered by Uncontrolled Human Immunodeficiency Virus

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    Bryan P. Fitzgerald

    2017-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening, rapidly progressive hematologic disorder involving uncontrolled immune system activation. HLH has been associated with viral infections, including human immunodeficiency virus (HIV infections. We report a case of a critically ill 30-year-old female who was hospitalized with HIV-associated HLH, with a CD4 count of 4 cells/mL and HIV viral load of 1,842,730 copies/mL. After ruling out other potential infectious causes of HLH, antiretroviral therapy (ART was initiated with darunavir, ritonavir, tenofovir, and emtricitabine. Within one week of initiation of ART, the patient began to improve clinically and hematologically and was stable enough for discharge from the hospital three weeks after starting therapy. This case suggests that treatment with ART in patients with HIV-associated HLH should be considered even in critically ill patients with low CD4 counts.

  9. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

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    Lohse, Nicolai; Jørgensen, LB; Kronborg, G

    2007-01-01

    OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients...... range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus ... in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk...

  10. Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy

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    Kirk, Ole; Reiss, Peter; Uberti-Foppa, Caterina

    2002-01-01

    maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. DESIGN: Observational study. SETTING: Seven European HIV cohorts. PATIENTS: 358...... identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte....... One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1...

  11. Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM

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    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec

    2015-01-01

    count 350/μl. We investigated what would be required to reduce HIV incidence in MSM to below 1 per 1000 person-years (i.e. cost-effective. METHODS: A dynamic, individual-based simulation model was calibrated to multiple data sources...... with viral suppression to 80%, and it would be 90%, if ART is initiated at diagnosis. The scenarios required for such a policy to be cost-effective are presented. CONCLUSION: This analysis provides targets for the proportion of all HIV-positive MSM with viral suppression required to achieve substantial......BACKGROUND: Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell...

  12. Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease

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    Borges, Álvaro H; Weitz, Jeffrey I; Collins, Gary

    2014-01-01

    OBJECTIVE: The objective of this study is to determine the relationship between inflammatory interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] and coagulation (D-dimer) biomarkers and the presence and type of anaemia among HIV-positive individuals. DESIGN: A cross-sectional...... study. METHODS: Combination antiretroviral therapy (cART)-treated adults participating in an international HIV trial with haemoglobin and mean corpuscular volume (MCV) measurements at entry were categorized by presence of anaemia (haemoglobin ≤14 g/dl in men and ≤12 g/dl in women) and, for those...... with anaemia, by type [microcytic (MCV 100 fl)]. We analysed the association between inflammation (IL-6 and hsCRP) and coagulation (D-dimer) and haemoglobin, controlling for demographics (age, race and sex), BMI, HIV plasma RNA levels, CD4⁺ T-cell counts (nadir...

  13. Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

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    Hijazi, Karolin; Cuppone, Anna M; Smith, Kieron; Stincarelli, Maria A; Ekeruche-Makinde, Julia; De Falco, Giulia; Hold, Georgina L; Shattock, Robin; Kelly, Charles G; Pozzi, Gianni; Iannelli, Francesco

    2015-01-01

    Anti-retroviral (ARV) -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on expression of drug

  14. Determining eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte counts, hemoglobin and body mass index

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    Solberg Peter

    2007-01-01

    Full Text Available Abstract Background CD4+ T lymphocyte (CD4 cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART, but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb, and body mass index (BMI to identify patients who require ART. Methods We conducted a cross-sectional study of HIV-infected adults in Uganda, who presented for assessment for ART-eligibility with WHO clinical stages I, II or III. Two by two tables were constructed to examine TLC thresholds, which maximized sensitivity for CD4 cell counts ≤ 200 cells μL, while minimizing the number offered ART with counts > 350 cells μL. Hb and BMI values were then examined to try to improve model performance. Results 1787 subjects were available for analysis. Median CD4 cell counts and TLCs, were 239 cells/μL and 1830 cells/μL, respectively. Offering ART to all subjects with a TLCs ≤ 2250 cells/μL produced a sensitivity of 0.88 and a false positive ratio of 0.21. Algorithms that treated all patients with a TLC 3000 cells/μL, and used Hb and/or BMI values to determine eligibility for those with TLC values between 2000 and 3000 cells/μL, marginally improved accuracy. Conclusion TLCs appear useful in predicting who would be eligible for ART based on CD4 cell count criteria. Hb and BMI values may be useful in prioritizing patients for ART, but did not improve model accuracy.

  15. A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy.

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    Araínga, Mariluz; Edagwa, Benson; Mosley, R Lee; Poluektova, Larisa Y; Gorantla, Santhi; Gendelman, Howard E

    2017-03-09

    Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1 ADA -infected NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency. At 6 weeks of infection animals were divided into four groups. One received long-acting (LA) cabotegravir (CAB) and rilpivirine (RVP) (2ART), a second received LA CAB, lamivudine, abacavir and RVP (4ART), a third were left untreated and a fourth served as an uninfected control. After 4 weeks of LA ART treatment, blood, spleen and bone marrow (BM) cells were collected then phenotypically characterized. CD4+ T cell subsets, macrophages and hematopoietic progenitor cells were analyzed for HIV-1 nucleic acids by droplet digital PCR. Plasma viral loads were reduced by two log 10 or to undetectable levels in the 2 and 4ART regimens, respectively. Numbers and distributions of CD4+ memory and regulatory T cells, macrophages and hematopoietic progenitor cells were significantly altered by HIV-1 infection and by both ART regimens. ART reduced viral DNA and RNA in all cell and tissue compartments. While memory cells were the dominant T cell reservoir, integrated HIV-1 DNA was also detected in the BM and spleen macrophages in both regimen-treated mice. Despite vigorous ART regimens, HIV-1 DNA and RNA were easily detected in mature macrophages supporting their potential role as an infectious viral reservoir.

  16. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

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    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-05-17

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should

  17. Predicting Malawian Women's Intention to Adhere to Antiretroviral Therapy.

    Science.gov (United States)

    McKinney, Ogbochi; Modeste, Naomi N; Lee, Jerry W; Gleason, Peter C

    2015-07-16

    With the increase in scaling up of antiretroviral therapy (ART), knowledge of the need for adherence to ART is pivotal for successful treatment outcomes. A cross-sectional study was carried out between October and December 2013. We administered theory of planned behaviour (TPB) and adherence questionnaires to 358 women aged 18-49 years, from a rural and urban ART-clinics in southern Malawi. Hierarchical linear regression models were used to predict intentions to adhere to ART. Regression models show that attitude (β=0.47), subjective norm (β=0.31) and perceived behavioural control (β=0.12) explain 55% of the variance in intentions to adhere to ART. The relationship between both food insecurity and perceived side effects with intentions to adhere to ART is mediated by attitude, subjective norm, and perceived behavioural control. Household (r=0.20) and individual (r=0.21) food insecurity were positively and significantly correlated with perceived behavioural control. Household food insecurity had a negative correlation with perceived side effects (r=-0.11). Perceived side effects were positively correlated with attitude (r=0.25). There was no statistically significant relationship between intentions to adhere to ART in the future and one month self-report of past month adherence. These interactions suggest that attitude predicted adherence only when food insecurity is high or perception of side effects is strong. This study shows that modification might be needed when using TPB constructs in resource constraint environments. Significance for public healthThe knowledge of the rates of adherence to antiretroviral therapy (ART) could be used to evaluate planning and project, which could lead to better outcomes predicted by treatment efficacy data. In addition, knowledge of adherence behaviour could help the development of interventions focusing on collaboration between healthcare providers and Malawian government to provide food support for patients on ART. The

  18. Study of determinants of Adherence to Antiretroviral Treatment among HIV Patients covered by Ahwaz Jundishapur University of Medical Sciences

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    Ahmad Moradi

    2016-11-01

    Full Text Available Adherence to antiretroviral therapy is essential for achieving durable clinical outcomes in patients with HIV. In addition, suboptimal adherence can accelerate development of drug-resistant HIV and mitigate HAART’s role in reducing HIV incidence and transmission. The present research has been conducted to study treatment adherence and determine its effective factors on HIV/AIDS patients with the support of Ahvaz JundiShapur University of Medical Sciences in 2015. This is a cross-sectional study in which 158 HIV/AIDS patients who had been registered in the counseling centers of behavioral diseases of Ahvaz and were receiving antiretroviral treatment. They had been selected by census method. Data were collected using the AACTG (Adult Aids Clinical Trials Group questionnaire. The collected data was analyzed and interpreted using descriptive statistical tests, χ2 and step by step regression by spss-16 software. The mean age of patients was 32.8±10.36. Among them 20.8% were female, 47.5% were single and 35.6% had a job. Also 33.7% of the respondents had CD4+ cell count less than 350 cells/μL. and average treatment duration was 9 months at study entry. According to the findings of this study, the degree of adherence was reported as % 63.9.The main reasons for non-adherence were forgetfulness (26% and side effects (19%. There were no significant differences between highly adherent and less adherent patients with regard to age, gender, education Employment status, Treatment duration, time of diagnosis. Adherence to HAART is a key factor in disease course in persons with HIV/AIDS. Low-level adherence in subjects of the study indicated that educational and intervention is quite necessary for patients in order to improve their medication self-management.

  19. Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe.

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    Mqondisi Tshabalala

    Full Text Available The rapid scale-up of highly active antiretroviral therapy (HAART and use of single dose Nevirapine (SD NVP for prevention of mother-to-child transmission (pMTCT have raised fears about the emergence of resistance to the first line antiretroviral drug regimens. A cross-sectional study was conducted to determine the prevalence of primary drug resistance (PDR in a cohort of young (<25 yrs HAART-naïve HIV pregnant women attending antenatal clinics in Chitungwiza, Zimbabwe. Whole blood was collected in EDTA for CD4 counts, viral load, serological estimation of duration of infection using the BED Calypte assay and genotyping for drug resistance. Four hundred and seventy-one women, mean age 21 years; SD: 2.1 were enrolled into the study between 2006 and 2007. Their median CD4 count was 371cells/µL; IQR: 255-511 cells/µL. Two hundred and thirty-six samples were genotyped for drug resistance. Based on the BED assay, 27% were recently infected (RI whilst 73% had long-term infection (LTI. Median CD4 count was higher (p<0.05 in RI than in women with LTI. Only 2 women had drug resistance mutations; protease I85V and reverse transcriptase Y181C. Prevalence of PDR in Chitungwiza, 4 years after commencement of the national ART program remained below WHO threshold limit (5%. Frequency of recent infection BED testing is consistent with high HIV acquisition during pregnancy. With the scale-up of long-term ART programs, maintenance of proper prescribing practices, continuous monitoring of patients and reinforcement of adherence may prevent the acquisition and transmission of PDR.

  20. Impact of injecting drug use on response to highly active antiretroviral treatment in HIV-1-infected patients: a nationwide population-based cohort study

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    Larsen, Mette Vang; Omland, Lars; Gerstoft, Jan

    2010-01-01

    The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted...... for non-IDUs, and IDUs initiated HAART later than non-IDUs. In conclusion, more than half of the HIV-infected patients in Denmark infected through injecting drug use gained full viral suppression after initiating HAART. Absolute CD4(+) cell count was lower and mortality higher among IDUs than non-IDUs....

  1. Início da terapia anti-retroviral em estágio avançado de imunodeficiência entre indivíduos portadores de HIV/AIDS em Belo Horizonte, Minas Gerais, Brasil Initiation of antiretroviral therapy in HIV-infected patients with severe immunodeficiency in Belo Horizonte, Minas Gerais State, Brazil

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    José Roberto Maggi Fernandes

    2009-06-01

    Full Text Available O objetivo deste trabalho foi verificar a proporção de início tardio da terapia anti-retroviral (TARV e seus fatores associados. Estudo de corte transversal com pacientes de dois serviços públicos de referência (n = 310 em Belo Horizonte, Minas Gerais, Brasil. Atraso no início da TARV foi definido como ter contagem de linfócitos T CD4+ The main objective was to assess the proportion of delayed initiation of antiretroviral therapy (ART and associated factors. This was a cross-sectional study of 310 patients enrolled in two public health centers in Belo Horizonte, Minas Gerais State, Brazil. Delayed ART initiation was defined as starting treatment with a CD4 count lower than 200 cells/mm³ or clinical symptoms of severe immunodepression at the time of first antiretroviral prescription. The majority of participants were males (63.9%, had no health insurance (76.1%, and started ART less than 120 days after the first medical visit (75.2%. The proportion of delayed ART initiation was 68.4%. Unemployment, referral by a health professional for HIV testing, fewer than two medical visits in the six months prior to ART initiation, and time between first medical visit and ART initiation less than 120 days were independently associated with the outcome. Our results suggest that every patient 13 to 64 years of age should be offered HIV testing, which could increase the rate of early HIV diagnosis, and thus patients that tested positive could benefit from timely follow-up and antiretroviral therapy.

  2. Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy

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    Ostrowski, Sisse R; Katzenstein, Terese L; Thim, Per T.

    2005-01-01

    Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined....

  3. Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

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    B P Muzah

    2012-10-01

    Full Text Available Background. The therapeutic goal of antiretroviral therapy (ART is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral suppression. Such discordant immune responses have been associated with poor clinical outcomes. Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation. Methods. Data were analysed from 810 HIV-infected adults initiated on first-line ART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs to determine associations between discordant immune response and clinical and demographic factors. Results. At ART initiation, 65% (n=592 of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm3, 70% (n=645 of patients had a haemoglobin level >11 g/dl and 88% (n=803 were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP. Six months after ART initiation, 24% (n=220 of patients had a discordant immune response and 7% (n=67 a discordant virological response. On multivariate analysis, baseline CD cell count ≥200 cells/mm3 (AOR 3.02; 95% confidence interval (CI 2.08 - 4.38; p

  4. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment.

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    Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

    2016-03-27

    Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4 cell count increase following its reinitiation in chronic infection (CHI). Longitudinal observational study. We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as 'pretreated in EHI' if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4 cell count (∼80 cells/μl; P treatment (re)initiation. Assuming common baseline CD4 cell count, differences in CD4 cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

  5. A STUDY OF ANTIRETROVIRAL THERAPY OUTCOMES IN A TERTIARY CARE CENTER IN THANJAVUR MEDICAL COLLEGE HOSPITAL, SOUTHERN INDIA

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    Kannan V. P

    2017-05-01

    Full Text Available BACKGROUND The number of people infected with the Human Immunodeficiency Virus (HIV worldwide was estimated to be 33.2 million at the end of 2007. The introduction of Anti-Retroviral Therapy (ART has significantly reduced morbidity and mortality in HIVinfected patients in various developed and developing countries. However, the outcome of ART in India’s National ART Programme has not been reported in detail. The aim of the study is to- 1. Evaluate the immunological response of HIV infected adults starting Highly Active Antiretroviral Therapy (HAART. 2. Evaluate the clinical response of highly active antiretroviral therapy in HIV infected adults. 3. Assess the functional status improvement following highly active antiretroviral therapy. MATERIALS AND METHODS To evaluate the effectiveness of the National ART Programme at Thanjavur Medical College Hospital, we undertook a prospective observational study involving ART naive patients who were started on ART between May 2015 and October 2016. ART was offered to these patients in accordance with NACO guidelines. The regimen consisted of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor. The available drugs included efavirenz, lamivudine, nevirapine and zidovudine. The CD4+ lymphocyte (CD4 count (cells/µL was estimated at baseline and at six months intervals during follow-up. Prophylaxis and treatment of opportunistic infections were in accordance with NACO guidelines. Anti-tuberculosis treatment was administered according to the Revised National Tuberculosis Control Programme guidelines. RESULTS Among 203 patients started on ART in this study, 3 died after completing 6 months of therapy and 17 died within 6 months of therapy. Out of the remaining 183 patients, 104 were males and 79 were females. The predominant route of HIV transmission is through unsafe sexual practice, which accounts for 84% of cases. Incidence of HIV is less common in literate

  6. Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda

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    Sempa Joseph

    2012-09-01

    Full Text Available Abstract Background Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART at CD4+ T cell (CD4 count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250–350 cell/μl (early versus Methods Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually. Results Treatment delay varied from 6–18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33–3.10 disability adjusted life years (DALY’s per patient. Lifetime treatment costs were $4,300–$5,248 for early initiation and $3,940–$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260–$270. Conclusions In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

  7. Predictive Utility of Brief AUDIT for HIV Antiretroviral Medication Nonadherence

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    Broyles, Lauren Matukaitis; Gordon, Adam J.; Sereika, Susan M.; Ryan, Christopher M.; Erlen, Judith A.

    2012-01-01

    Alcohol use negatively affects adherence to antiretroviral therapy (ART), thus HIV/AIDS providers need accurate, efficient assessments of alcohol use. Using existing data from an efficacy trial of two cognitive-behavioral ART adherence interventions, we sought to determine if results on two common alcohol screening tests (Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its binge-related question (AUDIT-3)) predict ART nonadherence. Twenty seven percent of the sample (n=308) were positive on the AUDIT-C and 34% were positive on the AUDIT-3. In multivariate analyses, AUDIT-C positive status predicted ART nonadherence after controlling for race, age, conscientiousness, and self-efficacy (p=.036). While AUDIT-3 positive status was associated with ART nonadherence in unadjusted analyses, this relationship was not maintained in the final multivariate model. The AUDIT-C shows potential as an indirect screening tool for both at-risk drinking and ART nonadherence, underscoring the relationship between alcohol and chronic disease management. PMID:22014256

  8. Review of differentiated approaches to antiretroviral therapy distribution.

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    Davis, Nicole; Kanagat, Natasha; Sharer, Melissa; Eagan, Sabrina; Pearson, Jennifer; Amanyeiwe, Ugochukwu Ugo

    2018-02-22

    In response to global trends of maximizing the number of patients receiving antiretroviral therapy (ART), this review summarizes literature describing differentiated models of ART distribution at facility and community levels in order to highlight promising strategies and identify evidence gaps. Databases and gray literature were searched, yielding thirteen final articles on differentiated ART distribution models supporting stable adult patients. Of these, seven articles focused on distribution at facility level and six at community level. Findings suggest that differentiated models of ART distribution contribute to higher retention, lower attrition, and less loss to follow-up (LTFU). These models also reduced patient wait time, travel costs, and time lost from work for drug pick-up. Facility- and community-level ART distribution models have the potential to extend treatment availability, enable improved access and adherence among people living with HIV (PLHIV), and facilitate retention in treatment and care. Gaps remain in understanding the desirability of these models for PLHIV, and the need for more information the negative and positive impacts of stigma, and identifying models to reach traditionally marginalized groups such as key populations and youth. Replicating differentiated care so efforts can reach more PLHIV will be critical to scaling these approaches across varying contexts.

  9. Thymidine analogue-sparing highly active antiretroviral therapy (HAART).

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    Nolan, David; Mallal, Simon

    2003-02-01

    The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.

  10. Generic substitution of antiretrovirals: patients' and health care providers' opinions.

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    Kieran, Jennifer A; O'Reilly, Eimear; O'Dea, Siobhan; Bergin, Colm; O'Leary, Aisling

    2017-10-01

    There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients' and providers' knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. An increase in dosing frequency (76%) or an increase in pill burden (50%) would make HCPs less likely to prescribe a generic ARV. The main perceived advantage was financial. Generic substitution of ARVs would be acceptable to the majority of patients and HCPs. Reinvesting savings back into HIV services would facilitate the success of such a programme.

  11. Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy.

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    Griffins O Manguro

    Full Text Available Genital ulcer disease (GUD prevalence increases in the first month of antiretroviral treatment (ART, followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2, we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation.We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment.At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period.Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation.

  12. An information system to manage the rollout of the antiretroviral treatment programme in the Free State

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    J.E. Kotzé

    2010-09-01

    Full Text Available The Acquired Immune Deficiency Syndrome epidemic, caused by the Human Immunodeficiency Virus, is a global crisis which threatens development gains, economies, and societies. Within sub-Saharan Africa, where the epidemic began the earliest and the HIV prevalence is the highest, African countries have death rates not seen before. In South Africa the epidemic has a devastating impact which creates profound suffering on individuals and their families, and the impact on the socio-economic level is of great concern. The eradication of HIV/AIDS represents one of humanity’s greatest challenges, which requires co-operation and comprehensive collaboration between many different role players. In this endeavour clinical information plays a major role. To combat the effect of the disease, the Free State Department of Health started with the provisioning of antiretroviral therapy in the public health sector. The objective of this paper was to address the challenges they faced in order to develop and implement an information system to manage the rollout of antiretroviral treatment effectively. They started with a paper-based system to collect vital information. It was followed by a palm computer project that was initiated to electronically capture the data collected by the paper-based system. This system was then replaced by a comprehensive Hospital and Clinic Information System which was acquired and customised for the antiretroviral data collection process. Research partners developed a standalone antiretroviral data warehouse for collecting information associated with the monitoring and evaluation of the Free State antiretroviral and HIV/ AIDS treatment programme. The data warehouse successfully produced several management information reports to the antiretroviral management team. A need was identified to design a comprehensive antiretroviral data warehouse that will integrate data from several operational sources which are all associated with HIV/AIDS.

  13. Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

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    Eshleman, Susan H; Laeyendecker, Oliver; Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C; Serwadda, David; Reynolds, Steven J; Kiwanuka, Noah; Quinn, Thomas C; Gray, Ronald; Wawer, Maria

    2009-04-27

    To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B

  14. Population uptake of antiretroviral treatment through primary care in rural South Africa

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    Bärnighausen Till W

    2010-09-01

    Full Text Available Abstract Background KwaZulu-Natal is the South African province worst affected by HIV and the focus of early modeling studies investigating strategies of antiretroviral treatment (ART delivery. The reality of antiretroviral roll-out through primary care has differed from that anticipated and real world data are needed to inform the planning of further scaling up of services. We investigated the factors associated with uptake of antiretroviral treatment through a primary healthcare system in rural South Africa. Methods Detailed demographic, HIV surveillance and geographic information system (GIS data were used to estimate the proportion of HIV positive adults accessing antiretroviral treatment within northern KwaZulu-Natal, South Africa in the period from initiation of antiretroviral roll-out until the end of 2008. Demographic, spatial and socioeconomic factors influencing the likelihood of individuals accessing antiretroviral treatment were explored using multivariable analysis. Results Mean uptake of ART among HIV positive resident adults was 21.0% (95%CI 20.1-21.9. Uptake among HIV positive men (19.2% was slightly lower than women (21.8%, P = 0.011. An individual's likelihood of accessing ART was not associated with level of education, household assets or urban/rural locale. ART uptake was strongly negatively associated with distance from the nearest primary healthcare facility (aOR = 0.728 per square-root transformed km, 95%CI 0.658-0.963, P = 0.002. Conclusions Despite concerns about the equitable nature of antiretroviral treatment rollout, we find very few differences in ART uptake across a range of socio-demographic variables in a rural South African population. However, even when socio-demographic factors were taken into account, individuals living further away from primary healthcare clinics were still significantly less likely to be accessing ART

  15. Risk factors for intestinal parasitosis among antiretroviral-treated HIV/AIDS patients in Ethiopia.

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    Mahmud, Mahmud Abdulkader; Bezabih, Afework Mulugeta; Gebru, Rezene Berhe

    2014-10-01

    Summary A cross-sectional survey was conducted to determine the risk factors associated with intestinal parasitosis in HIV/AIDS patients receiving antiretroviral therapy (ART). Socio-demographic information was collected and faecal samples were analysed from 384 randomly selected patients on ART. Data on CD4+ T-cell counts and World Health Organization clinical staging were obtained from the medical records at the hospital. The overall prevalence of intestinal parasitosis was 56% (95% confidence interval [CI]: 51% to 61%). No opportunistic intestinal parasites or Schistosoma haematobium eggs were detected. Unavailability of latrine and lack of hand washing with soap were associated with Entamoeba histolytica/dispar (adjusted odds ratio [AOR], 2.75; 95% CI: 1.77 to 4.27 and AOR, 2.67; 95% CI: 1.60 to 4.44, respectively) and Giardia lamblia (AOR, 2.08; 95% CI: 1.08 to 3.99 and AOR, 2.46; 95% CI: 1.06 to 5.75, respectively) infections. Intestinal parasitosis was significantly associated with low CD4 cell count (p = 0.002). In contrast, intestinal parasitic infections were not associated (p > 0.05) with the World Health Organization disease staging. In summary, poor personal hygiene and sanitation practice contributed to the high prevalence of intestinal parasitosis. Routine diagnosis for intestinal parasitic infections should be performed in patients attending ART clinics in this setting. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. The Immune Pathogenesis of Immune Reconstitution Inflammatory Syndrome Associated with Highly Active Antiretroviral Therapy in AIDS

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    Zhou, Huaying; He, Yan; Chen, Zi; He, Bo; He, Mei

    2014-01-01

    Abstract The present study investigated the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome (AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total of 238 patients with AIDS who received initial HAART were included in this prospective cohort study. Blood samples were collected immediately, at baseline, at week 12, and at week 24 after initial HAART and at the onset of IRIS. Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were measured by flow cytometry or ELISA. Among the 238 patients with AIDS who received HAART, 47 patients developed IRIS. The percentages of CD4+ and CD8+ naive, memory, and activated cells exhibited no significant differences between AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage of CD4+CD25+Foxp3+ regulatory T cells was lower in IRIS patients than in non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and at the onset of IRIS. IL-2 and interferon (IFN)-γ levels were significantly higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7 decreased gradually with the progression of HAART. The level of IL-7 was higher in IRIS patients than in non-IRIS patients at all follow-up time points. An imbalance of Th1/Th2 cytokines, a consistently low CD+CD25+Fox3+ percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in AIDS patients who had received HAART. PMID:25131160

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

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    Weijun Zhu

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

  18. Risk factors for mortality in a south Indian population on generic antiretroviral therapy.

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    Rupali, Priscilla; Mannam, Sam; Bella, Annie; John, Lydia; Rajkumar, S; Clarence, Peace; Pulimood, Susanne A; Samuel, Prasanna; Karthik, Rajiv; Abraham, Ooriapadickal Cherian; Mathai, Dilip

    2012-12-01

    Antiretroviral treatment (ART) programs from low-income countries utilizing standardized ART regimens, simplified approaches to clinical decision making and basic lab monitoring have reported high mortality rates. We determined the risk factors for mortality among HIV-infected adults following the initiation of ART from a single center in south India. ART-naive HIV-infected south Indian adults attending the Infectious Diseases clinic in a 2000-bed academic medical center in south India who were initiated on ART (generic, fixed-dose combinations) as per the national guidelines were followed up. Cases (32 patients who died) were compared with age and sex matched controls. Eight-hundred and twenty-two patients were started on ART from January 1, 2000 to December 31, 2008. The cumulative mortality was 6.8% (56/822). Among the cases mean age was 44 years, 18% were women and mean CD4 counts was 107 cells/microl. Among the controls mean age was 41 years, 18% were women and mean CD4 counts were 113 cells/microl. Stavudine based ART was predominant 62.5% in the cases vs 37.5% in the controls, followed by zidovudine based therapy in 31.2% of cases and 43.7% in the controls. Tenofovir based therapy was used in 6.2% of cases vs 18.7% in the controls. The commonest causes of death were drug toxicity 19%, advanced Acquired Immunodeficiency Syndrome (AIDS) in 37%, Immune Reconstitution Inflammatory Syndrome (IRIS) in 16%, non AIDS related deaths in 22% and malignancies 6%. In a univariate analysis, absolute lymphocyte count ART (p=0.001) were significantly associated with mortality. The mortality among our patients was comparable to that reported from other low-income countries. Earlier initiation of ART may reduce the high mortality rates observed.

  19. Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy.

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    Yanik, Elizabeth L; Napravnik, Sonia; Cole, Stephen R; Achenbach, Chad J; Gopal, Satish; Olshan, Andrew; Dittmer, Dirk P; Kitahata, Mari M; Mugavero, Michael J; Saag, Michael; Moore, Richard D; Mayer, Kenneth; Mathews, W Christopher; Hunt, Peter W; Rodriguez, Benigno; Eron, Joseph J

    2013-09-01

    Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized. We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation. At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence. KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

  20. Early initiation of antiretroviral treatment: Challenges in the Middle East and North Africa.

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    Sardashti, Sara; Samaei, Mehrnoosh; Firouzeh, Mona Mohammadi; Mirshahvalad, Seyed Ali; Pahlaviani, Fatemeh Golsoorat; SeyedAlinaghi, SeyedAhmad

    2015-05-12

    New World Health Organization guidelines recommend the initiation of antiretroviral treatment (ART) for asymptomatic patients with CD4+ T-cell counts of ≤ 500 cells/mm(3). Substantial reduction of human immunodeficiency virus (HIV) transmission is addressed as a major public health outcome of this new approach. Middle East and North Africa (MENA), known as the area of controversies in terms of availability of comprehensive data, has shown concentrated epidemics among most of it's at risk population groups. Serious challenges impede the applicability of new guidelines in the MENA Region. Insufficient resources restrict ART coverage to less than 14%, while only one fourth of the countries had reportable data on patients' CD4 counts at the time of diagnosis. Clinical guidelines need to be significantly modified to reach practical utility, and surveillance systems have not yet been developed in many countries of MENA. Based on available evidence in several countries people who inject drugs and men who have sex with men are increasingly vulnerable to HIV and viral hepatitis, while their sexual partners - either female sex workers or women in monogamous relationships with high-risk men - are potential bridging populations that are not appropriately addressed by regional programs. Research to monitor the response to ART among the mentioned groups are seriously lacking, while drug resistant HIV strains and limited information on adherence patterns to treatment regimens require urgent recognition by health policymakers. Commitment to defined goals in the fight against HIV, development of innovative methods to improve registration and reporting systems, monitoring and evaluation of current programs followed by cost-effective modifications are proposed as effective steps to be acknowledged by National AIDS Programs of the countries of MENA Region.

  1. Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy in colonized epithelial multilayer cultures.

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    Pyles, Richard B; Vincent, Kathleen L; Baum, Marc M; Elsom, Barry; Miller, Aaron L; Maxwell, Carrie; Eaves-Pyles, Tonyia D; Li, Guangyu; Popov, Vsevolod L; Nusbaum, Rebecca J; Ferguson, Monique R

    2014-01-01

    There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral.

  2. Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

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    Whiteman, Maura K; Jeng, Gary; Samarina, Anna; Akatova, Natalia; Martirosyan, Margarita; Kissin, Dmitry M; Curtis, Kathryn M; Marchbanks, Polly A; Hillis, Susan D; Mandel, Michele G; Jamieson, Denise J

    2016-01-01

    To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to contraceptive method. During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Published by Elsevier Inc.

  3. Antiretroviral treatment program retention among HIV-infected children in the Democratic Republic of Congo.

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    John Ditekemena

    Full Text Available BACKGROUND: Retaining patients with HIV infection in care is still a major challenge in sub- Saharan Africa, particularly in the Democratic Republic of Congo (DRC where the antiretroviral treatment (ART coverage is low. Monitoring retention is an important tool for evaluating the quality of care. METHODS AND FINDINGS: A review of medical records of HIV-infected children was performed in three health facilities in the DRC: the Amo-Congo Health center, the Monkole Clinic in Kinshasa, and the HEAL Africa Clinic in Goma. Medical records of 720 children were included. Kaplan Meier curves were constructed with the probability of retention at 6 months, 1 year, 2 years and 3 years. Retention rates were: 88.2% (95% CI: 85.1%-90.8% at 6 months; 85% (95% CI: 81.5%-87.6% at one year; 79.4% (95%CI: 75.5%-82.8% at two years and 74.7% (95% CI: 70.5%-78.5% at 3 years. The retention varied across study sites: 88.2%, 66.6% and 92.5% at 6 months; 84%, 59% and 90% at 12 months and 75.7%, 56.3% and 85.8% at 24 months respectively for Amo-Congo/Kasavubu, Monkole facility and HEAL Africa. After multivariable Cox regression four variables remained independently associated with attrition: study site, CD4 cell count <350 cells/µL, children younger than 2 years and children whose caregivers were member of an independent church. CONCLUSIONS: Attrition remains a challenge for pediatric HIV positive patients in ART programs in DRC. In addition, the low coverage of pediatric treatment exacerbates the situation of pediatric HIV/AIDS.

  4. Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice.

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    Paul W Denton

    2008-01-01

    Full Text Available Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection.We show that the female reproductive tract of humanized bone marrow-liver-thymus (BLT mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT that closely mimics what is observed in HIV-1-infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8 of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5 given pre-exposure prophylaxis of emtricitabine (FTC/tenofovir disoproxil fumarate (TDF showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006.The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.

  5. Immunological and virological changes in antiretroviral naïve human immunodeficiency virus infected patients randomized to G-CSF or placebo simultaneously with initiation of HAART

    DEFF Research Database (Denmark)

    Aladdin, H; Ullum, H; Katzenstein, T

    2000-01-01

    To determine the efficacy of combined G-CSF and highly active antiretroviral treatment (HAART), a randomized, double blind, placebo controlled study was conducted. Treatment naive human immunodeficiency virus (HIV) infected patients were randomized to receive either placebo or G-CSF (0.3 mg/ml, 3...... = 6) or placebo group (n = 5). In both groups plasma HIV RNA decreased significantly in response to HAART. However, plasma HIV RNA changed significantly different between the two groups with the decrease being less pronounced in the G-CSF group (P = 0.02). The concentrations of CD4+ memory T cells...... and CD8+ naive and memory T cells increased in response to HAART, and there was a trend towards more pronounced increases in several T-cell subpopulations in the G-CSF group. The CD56+ NK cells increased significantly more in the G-CSF group compared with placebo (P = 0. 000). All patients in the G...

  6. Immune activation in HIV-infected aging women on antiretrovirals--implications for age-associated comorbidities: a cross-sectional pilot study.

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    Maria L Alcaide

    Full Text Available Persistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages.Twenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163, microbial translocation (LPS and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10 were evaluated.T cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation.HIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls.

  7. Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

    Science.gov (United States)

    Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

    2014-11-01

    Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

  8. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

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    Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjecha, Michael J

    2012-01-01

    Background Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/μL are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot phase was well underway, and the complexities of conducting the trial in a geographically wide

  9. Impact of a pharmaceutical care program on clinical evolution and antiretroviral treatment adherence: a 5-year study

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    Hernández Arroyo MJ

    2013-08-01

    considerable decrease in the percentage of patients with CD4+ lymphocytes less than 200 cells/mm3 (P < 0.001. A relationship was found between the number of patients with optimum adherence levels and the time that plasma viral load remained undetected. The number of interviews and interventions performed in each patient in the first 12 months from the onset of the pharmaceutical care program (month 6, was related to a significant increase in adherence during this same time period. Conclusion: The results suggest that the establishment and permanence of a pharmaceutical care program may increase ART adherence, increase permanence time of the patient with undetectable plasma viral loads, and improve patients' lymphocyte count. Keywords: pharmaceutical care, antiretroviral treatment adherence, undetectable PVLs, CD4+ lymphocyte count, adherence measures, HIV/AIDS

  10. Modeling of Antilatency Treatment in HIV: What Is the Optimal Duration of Antiretroviral Therapy-Free HIV Remission?

    Science.gov (United States)

    Cromer, Deborah; Pinkevych, Mykola; Rasmussen, Thomas A; Lewin, Sharon R; Kent, Stephen J; Davenport, Miles P

    2017-12-15

    A number of treatment strategies are currently being developed to promote antiretroviral therapy-free HIV cure or remission. While complete elimination of the HIV reservoir would prevent recurrence of infection, it is not clear how different remission lengths would affect viral rebound and transmission. In this work, we use a stochastic model to show that a treatment that achieves a 1-year average time to viral remission will still lead to nearly a quarter of subjects experiencing viral rebound within the first 3 months. Given quarterly viral testing intervals, this leads to an expected 39 (95% uncertainty interval [UI], 22 to 69) heterosexual transmissions and up to 262 (95% UI, 107 to 534) homosexual transmissions per 1,000 treated subjects over a 10-year period. Thus, a balance between high initial treatment levels, risk of recrudescence, and risk of transmission should be considered when assessing the "useful" or optimal length of antiretroviral therapy-free HIV remission to be targeted. We also investigate the trade-off between increasing the average duration of remission versus the risk of treatment failure (viral recrudescence) and the need for retreatment. To minimize drug exposure, we found that the optimal target of antilatency interventions is a 1,700-fold reduction in the size of the reservoir, which leads to an average time to recrudescence of 30 years. Interestingly, this is a significantly lower level of reduction than that required for complete elimination of the viral reservoir. Additionally, we show that when shorter periods are targeted, there is a real probability of viral transmission occurring between tests for viral rebound. IMPORTANCE Current treatment of HIV involves patients taking antiretroviral therapy to ensure that the level of virus remains very low or undetectable. Continuous therapy is required, as the virus persists in a latent state within cells, and when therapy is stopped, the virus rebounds, usually within 2 weeks. A major

  11. Self-reported adverse reactions among patients initiating antiretroviral therapy in Brazil

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    Cristiane A. Menezes de Pádua

    Full Text Available A cross-sectional analysis was carried out to describe adverse reactions to antiretroviral therapy (ART reported by HIV-infected patients initiating treatment at two public health AIDS referral centers in Belo Horizonte, Brazil, 2001-2003 and to verify their association with selected variables. Adverse reactions were obtained through interview at the first follow-up visit (first month after the antiretroviral prescription. Socio-demographic and behavioral variables related to ART were obtained from baseline and follow-up interviews and clinical variables from medical charts. Patients with four or more reactions were compared to those with less than four. Odds ratio with 95% confidence interval were estimated using logistic regression model for both univariate and multivariate analyses. At least one adverse reaction was reported by 92.2% of the participants while 56.2% reported four or more different reactions. Antiretroviral regimens including indinavir/ritonavir, irregular use of antiretrovirals and switch in regimens were independently associated with four or more adverse reactions (OR=7.92, 5.73 and 2.03, respectively. The initial period of ARV treatment is crucial and patients´ perception of adverse reactions should be carefully taken into account. Strategies for monitoring and management of adverse reactions including the choice of regimens and the prevention of irregular ART should be developed in AIDS/HIV referral centers in Brazil to promote better adherence to antiretroviral therapy.

  12. Treatment and prevention of HIV infection with long-acting antiretrovirals.

    Science.gov (United States)

    Benítez-Gutiérrez, Laura; Soriano, Vicente; Requena, Silvia; Arias, Ana; Barreiro, Pablo; de Mendoza, Carmen

    2018-05-01

    Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.

  13. Provision of antiretroviral treatment in conflict settings: the experience of Médecins Sans Frontières.

    Science.gov (United States)

    O'Brien, Daniel P; Venis, Sarah; Greig, Jane; Shanks, Leslie; Ellman, Tom; Sabapathy, Kalpana; Frigati, Lisa; Mills, Clair

    2010-06-17

    Many countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed. From 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned. In the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145). At analysis, 2645 (64%) remained on ART, 422 (10%) had died, 466 (11%) lost to follow-up, 417 (10%) transferred to another programme, and 195 (5%) had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3.Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities. With commitment, simplified treatment and monitoring, and adaptations for potential

  14. A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups.

    Science.gov (United States)

    Parathyras, John; Gebhardt, Stefan; Hillermann-Rebello, Renate; Grobbelaar, Nelis; Venter, Mauritz; Warnich, Louise

    2009-05-01

    South Africa, like many other Southern African countries, has one of the highest HIV infection rates in the world and many individuals consequently receive antiretroviral therapy (ART). However, knowledge regarding (i) the prevalence of functional single nucleotide polymorphisms (SNPs) in pharmacologically relevant genes, and (ii) variance in pharmacotherapy both within and between different populations and ethnic groups is limited. The aim of this study was to determine whether selected polymorphisms in cytochrome P450 (CYP) genes (CYP2B6 and CYP3A4) and the multidrug-resistance 1 (ABCB1) gene underlie altered antiretroviral (ARV) drug response in two South African populations. DNA samples from 182 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity on ART were genotyped for the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in ABCB1. Univariate two-way analysis of variance (ANOVA) testing revealed no apparent effect of ethnicity on immune recovery (in terms of CD4-cell count) in response to ART. Univariate one-way ANOVA testing revealed a discernible effect of genotype on immune recovery in the cases of the T-129C (P=0.03) and G2677A (P<0.01) polymorphisms in the ABCB1 gene. This study serves as a basis for better understanding and possible prediction of pharmacogenetic risk profiles and drug response in individuals and ethnic groups in South Africa.

  15. Provision of antiretroviral treatment in conflict settings: the experience of Médecins Sans Frontières

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    Ellman Tom

    2010-06-01

    Full Text Available Abstract Introduction Many countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed. Methods From 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned. Results In the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145. At analysis, 2645 (64% remained on ART, 422 (10% had died, 466 (11% lost to follow-up, 417 (10% transferred to another programme, and 195 (5% had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3. Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities. Conclusions With commitment, simplified

  16. Activity of antiretroviral drugs in human infections by opportunistic agents

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    Izabel Galhardo Demarchi

    2012-03-01

    Full Text Available Highly active antiretroviral therapy (HAART is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV, human herpes virus 8 (HHV-8, Epstein-Barr virus, hepatitis B virus (HBV, parvovirus B19 and cytomegalovirus (CMV. HAART has also led to a significant reduction in the incidence, and the modification of characteristics, of bacteremia by etiological agents such as Staphylococcus aureus, coagulase negative staphylococcus, non-typhoid species of Salmonella, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. HAART can modify the natural history of cryptosporidiosis and microsporidiosis, and restore mucosal immunity, leading to the eradication of Cryptosporidium parvum. A similar restoration of immune response occurs in infections by Toxoplasma gondii. The decline in the incidence of visceral leishmaniasis/HIV co-infection can be observed after the introduction of protease inhibitor therapy. Current findings are highly relevant for clinical medicine and may serve to reduce the number of prescribed drugs thereby improving the quality of life of patients with opportunistic diseases.A terapia HAART (terapia antirretroviral altamente ativa é usada em pacientes infectados pelo vírus da imunodeficiência humana (HIV e demonstrou diminuição significativa de infecções oportunistas, tais como as causadas por vírus, fungos, protozoários e bactérias. O uso da HAART está associado com a reconstituição imunológica e diminuição na prevalência de candidíase oral. A terapia antirretroviral beneficia pacientes co-infectados pelo HIV, v

  17. Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy

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    Leal Manuel

    2006-07-01

    Full Text Available Abstract Background Recent advances in characterizing the immune recovery of HIV-1-infected people have highlighted the importance of the thymus for peripheral T-cell diversity and function. The aim of this study was to investigate differences in immune reconstitution profiles after highly active antiretroviral therapy (HAART between HIV-children and adults. Methods HIV patients were grouped according to their previous clinical and immunological status: 9 HIV-Reconstituting-adults (HIV-Rec-adults and 10 HIV-Reconstituting-children (HIV-Rec-children on HAART with viral load (VL ≤400 copies/ml and CD4+ ≥500 cells/μL at least during 6 months before the study and CD4+ ≤300 cells/μL anytime before. Fifteen healthy-adults and 20 healthy-children (control subjects were used to calculate Z-score values to unify value scales between children and adults to make them comparable. Results HIV-Rec-children had higher T-cell receptor excision circles (TREC and lower interleukin (IL-7 levels than HIV-Rec-adults (p + (CD4+CD45RA hi+CD27+, naïve CD8+ (CD8+CD45RA hi+CD27+, and memory CD8+ (CD8+CD45RO+ cells/μl than HIV-Rec-adults, but similar memory CD4+ (CD4+CD45RO+ counts. HIV-Rec-children had lower naïve CD8+ Z-score values than HIV-Rec-adults (p = 0.05. Conclusion Our data suggest that HIV-Rec-children had better thymic function than HIV-Rec-adults and this fact affects the peripheral T-cell subsets. Thus, T-cell recovery after HAART in HIV-Rec-adults could be the consequence of antigen-independent peripheral T-cell expansion while in HIV-Rec-children thymic output could play a predominant role in immune reconstitution.

  18. Ex vivo response to histone deacetylase (HDAC inhibitors of the HIV long terminal repeat (LTR derived from HIV-infected patients on antiretroviral therapy.

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    Hao K Lu

    Full Text Available Histone deacetylase inhibitors (HDACi can induce human immunodeficiency virus (HIV transcription from the HIV long terminal repeat (LTR. However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+ isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART. We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.

  19. Barriers to Antiretroviral Initiation in HIV-1-Discordant Couples

    Science.gov (United States)

    Guthrie, Brandon L.; Choi, Robert Y.; Liu, Amy Y.; Mackelprang, Romel D.; Rositch, Anne F.; Bosire, Rose; Manyara, Lucy; Gatuguta, Anne; Kiarie, James N.; Farquhar, Carey

    2011-01-01

    BACKGROUND In Kenya and much of sub-Saharan Africa, nearly half of all couples affected by HIV are discordant. Antiretroviral therapy (ART) slows disease progression in HIV-1-infected individuals, and reduces transmission to uninfected partners. We examined time to ART initiation and factors associated with delayed initiation in HIV-1-discordant couples in Nairobi. METHODS HIV-1-discordant couples were enrolled and followed quarterly for up to 2 years. Clinical staff administered questionnaires and conducted viral loads and CD4 counts. Participants with a CD4 count meeting ART criteria were referred to a nearby PEPFAR-funded treatment center. Barriers to ART initiation among participants with a CD4 count eligible for ART were assessed by Cox regression. RESULTS Of 439 HIV-1-infected participants (63.6% females and 36.4% males) 146 met CD4 count criteria for ART during follow-up. Median time from meeting CD4 criteria until ART initiation was 8.9 months, with 42.0% of eligible participants on ART by 6 months and 63.4% on ART by 1 year. The CD4 count at the time of eligibility was inversely associated with time to ART initiation (HR=0.49, p< 0.001). Compared to homeowners, those paying higher rents started ART 48% more slowly (p=0.062) and those paying lower rents started 71% more slowly (p=0.002). CONCLUSIONS Despite access to regular health care, referrals to treatment centers, and free access to ART, over a third of participants with an eligible CD4 count had not started ART within 1 year. Factors of lower socioeconomic status may slow ART initiation and targeted approaches are needed to avoid delays in treatment initiation. PMID:21826010

  20. Multitype violence exposures and adolescent antiretroviral nonadherence in South Africa.

    Science.gov (United States)

    Cluver, Lucie; Meinck, Franziska; Toska, Elona; Orkin, F Mark; Hodes, Rebecca; Sherr, Lorraine

    2018-05-15

    HIV-positive adolescents have low-ART adherence, with consequent increased risks of mortality, morbidity, and viral resistance. Despite high rates of violence against children in the Africa region, no known studies have tested impacts on HIV-positive adolescents. We examine associations of ART adherence with adolescent violence victimization by caregivers, teachers, peers, community members, and healthcare providers. HIV-positive adolescents were interviewed (n = 1060), and clinic biomarker data collected. We sampled all 10-19-year olds ever ART-initiated within 53 clinics in 180 South African communities (90.1% reached). Analyses examined associations between nonadherence and nine violence types using sequential multivariate logistic regressions. Interactive and additive effects were tested with regression and marginal effects. Past-week self-reported ART nonadherence was 36%. Nonadherence correlated strongly with virologic failure (OR 2.3, CI 1.4-3.8) and symptomatic pulmonary tuberculosis (OR 1.49, CI 1.18-2.05). Four violence types were independently associated with nonadherence: physical abuse by caregivers (OR 1.5, CI 1.1-2.1); witnessing domestic violence (OR 1.8, CI 1.22-2.66); teacher violence (OR 1.51, CI 1.16-1.96,) and verbal victimization by healthcare staff (OR 2.15, CI 1.59-2.93). Past-week nonadherence rose from 25% with no violence to 73.5% with four types of violence exposure. Violence exposures at home, school, and clinic are major and cumulating risks for adolescent antiretroviral nonadherence. Prevention, mitigation, and protection services may be essential for the health and survival of HIV-positive adolescents.

  1. Contagiousness under antiretroviral therapy and stigmatization toward people with HIV.

    Science.gov (United States)

    Drewes, Jochen; Kleiber, Dieter

    2014-01-01

    Perceived contagiousness is a major dimension underlying HIV-related stigmatization. Antiretroviral therapy (ART) can diminish contagiousness by reducing viral load levels in HIV-infected individuals. To test the assumption that reductions in contagiousness can lead to a decrease in stigmatizing reactions, we conducted an experimental online study. A sample of 752 participants (50.9% female) read a short vignette depicting an HIV-positive individual with either a high or a low viral load and were either given or not given information about the association between viral load and contagiousness. Subsequently, participants were asked to rate their willingness to stigmatize this individual by responding to two measures of social and physical distance. Differences between the low and the high viral load information groups and the combined no-information groups (forming a quasi-control group) were analyzed using analysis of covariance (ANCOVA), controlling for gender and baseline perceptions of contagiousness. The covariates, perceived contagiousness at baseline and gender, were associated with social and physical distancing, but the viral load/information factor was only significant in physical distancing. Planned contrast analyses confirmed that physical distancing in the informed group was lower in the low viral load condition compared to the high viral load condition and to the control group. We thus found evidence for the significant role of perceived contagiousness in the HIV-related stigma and were able to experimentally demonstrate the potential of ART to reduce HIV-related stigmatization by lowering viral load and contagiousness, when these changes are accompanied by a decreased perception of contagiousness.

  2. Fate of the antiretroviral drug tenofovir in agricultural soil

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Chapman, Ralph; Lapen, David R.; Topp, Edward, E-mail: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON, N5V 4T3 (Canada)

    2010-10-15

    Tenofovir (9-(R)-(2-phosphonylmethoxypropyl)-adenine) is an antiretroviral drug widely used for the treatment of human immunodeficiency virus (HIV-1) and Hepatitis B virus (HBV) infections. Tenofovir is extensively and rapidly excreted unchanged in the urine. In the expectation that tenofovir could potentially reach agricultural lands through the application of municipal biosolids or wastewater, and in the absence of any environmental fate data, we evaluated its persistence in selected agricultural soils. Less than 10% of [adenine-8-{sup 14}C]-tenofovir added to soils varying widely in texture (sand, loam, clay loam) was mineralized in a 2-month incubation under laboratory conditions. Tenofovir was less readily extractable from clay soils than from a loam or a sandy loam soil. Radioactive residues of tenofovir were removed from the soil extractable fraction with DT{sub 50}s ranging from 24 {+-} 2 to 67 + 22 days (first order kinetic model) or 44 + 9 to 127 + 55 days (zero order model). No extractable transformation products were detectable by HPLC. Tenofovir mineralization in the loam soil increased with temperature (range 4 {sup o}C to 30 {sup o}C), and did not occur in autoclaved soil, suggesting a microbial basis. Mineralization rates increased with soil moisture content, ranging from air-dried to saturated. In summary, tenofovir was relatively persistent in soils, there were no extractable transformation products detected, and the response of [adenine-8-{sup 14}C]-tenofovir mineralization to soil temperature and heat sterilization indicated that the molecule was biodegraded by aerobic microorganisms. Sorption isotherms with dewatered biosolids suggested that tenofovir residues could potentially partition into the particulate fraction during sewage treatment.

  3. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group

    NARCIS (Netherlands)

    Pakker, N. G.; Kroon, E. D.; Roos, M. T.; Otto, S. A.; Hall, D.; Wit, F. W.; Hamann, D.; van der Ende, M. E.; Claessen, F. A.; Kauffmann, R. H.; Koopmans, P. P.; Kroon, F. P.; ten Napel, C. H.; Sprenger, H. G.; Weigel, H. M.; Montaner, J. S.; Lange, J. M.; Reiss, P.; Schellekens, P. T.; Miedema, F.

    1999-01-01

    BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  4. Uptake of combination antiretroviral therapy and HIV disease progression according to geographical origin in seroconverters in Europe, Canada, and Australia

    DEFF Research Database (Denmark)

    Jarrin, Inma; Pantazis, Nikos; Gill, M John

    2012-01-01

    We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART).......We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART)....

  5. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Neuhaus, Jacqueline; Duprez, Daniel

    2011-01-01

    Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compa...

  6. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies.

    Science.gov (United States)

    Johnson, Leigh F; Mossong, Joel; Dorrington, Rob E; Schomaker, Michael; Hoffmann, Christopher J; Keiser, Olivia; Fox, Matthew P; Wood, Robin; Prozesky, Hans; Giddy, Janet; Garone, Daniela Belen; Cornell, Morna; Egger, Matthias; Boulle, Andrew

    2013-01-01

    Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations. South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.

  7. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies.

    Directory of Open Access Journals (Sweden)

    Leigh F Johnson

    Full Text Available Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2 at age 20 y and 10.1 y (95% CI: 9.3-10.8 at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7 and 14.4 y (95% CI: 13.3-15.3, respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0 if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0 if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.

  8. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    International Nuclear Information System (INIS)

    Jiang Bo; Hebert, Valeria Y.; Li, Yuchi; Mathis, J. Michael; Alexander, J. Steven; Dugas, Tammy R.

    2007-01-01

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF 2α ) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF 2α production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production

  9. Antiretroviral treatment for HIV infection/AIDS and the risk of developing hyperglycemia and hyperlipidemia Tratamento antiretroviral para a infecção pelo HIV/AIDS e o risco de desenvolver hiperglicemia e dislipidemia

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio Ramos de Araújo

    2007-04-01

    Full Text Available A cross-sectional study with internal comparison groups was conducted to describe sociodemographic characteristics, as well as verify the association between the type of antiretroviral treatment used and hyperglycemia and hyperlipidemia, with special attention to the use of HIV protease inhibitors. The data was obtained through an interview questionnaire, as well as blood and urine samples that were collected for the laboratory exams. A total of 418 patients were interviewed. 46 of these, however, met the exclusion criteria. The sample was therefore composed by 372 HIV positive patients, attended at the laboratory of the Correia Picanço State Hospital for the collection of blood, to estimate the HIV viral load and/or TCD4 cell counts from August to November 2000. The association between the variables was tested using the chi-square test and the p-value. A multiple logistic regression analysis was carried out to adjust for potential confounding factors. A greater frequency of patients with high glucose levels was observed among those making use of antiretroviral therapy without protease inhibitors, but the number of patients limited the comparisons. An association was verified between the total serum cholesterol level and the use of HIV protease inhibitors (p = 0.047 even after controlling for age. An association was also observed between the triglyceride levels and the use of HIV protease inhibitors, which remained after adjustment for age, sex and creatinine levels (p Um estudo epidemiológico transversal, com caráter analítico, foi realizado para descrever características sócio-demográficas bem como verificar a associação entre o tipo de tratamento antiretroviral empregado e hiperglicemia e hiperlipidemia, com especial atenção aos pacientes em uso de inibidores da protease do HIV. As informações foram obtidas a partir de um questionário e da coleta de sangue e urina para a execução dos exames laboratoriais. Foram entrevistados

  10. Antiretroviral therapy during pregnancy and early neonatal life: consequences for HIV-exposed, uninfected children

    Directory of Open Access Journals (Sweden)

    Patrícia El Beitune

    Full Text Available Women have emerged as the fastest growing human immunodeficiency virus (HIV infected population worldwide, mainly because of the increasing occurrence of heterosexual transmission. Most infected women are of reproductive age and one of the greatest concerns for both women and their physicians is that more than 1,600 infants become infected with HIV each day. Almost all infections are a result of mother-to-child transmission of HIV. With the advent of combination antiretroviral therapies, transmission rates lower than 2% have been achieved in clinical studies. Antiretroviral compounds differ from most other new pharmaceutical agents in that they have become widely prescribed in pregnancy in the absence of proof of safety. We reviewed antiretroviral agents used in pregnant women infected with human immunodeficiency virus, mother-to-child transmission, and their consequences for infants.

  11. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review.

    Science.gov (United States)

    Cysique, Lucette A; Brew, Bruce J

    2009-06-01

    This article presents a review of studies that have investigated the neuropsychological effects of antiretroviral treatment (ART) for HIV-1 infection. It provides a brief overview of the era of monotherapy, dual-therapy, and an extended overview of the current era of combination antiretroviral therapy (CART). This review highlights that while CART has had a dramatic effect on the incidence and the severity of HIV-associated neurocognitive disorders (HAND), HAND, in its mild form, still remains prevalent. New causes of this sustained prevalence are poor CNS penetration of some antiretroviral agents, drug resistance, poor adherence, potential neurotoxicity, co-morbidities such as the long-term CART side effects in relation to cardio-vascular disease, and chronic HIV brain infection that may facilitate the expression of new forms of neurodegenerative processes. The review emphasizes the need to address methodological limitations of published studies and the need for large and representative cross-disciplinary longitudinal investigations across the HIV illness span.

  12. HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.

    Science.gov (United States)

    Kotler, Donald P

    2008-09-01

    It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

  13. 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...... 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......= -0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes (r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0...

  14. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study

    DEFF Research Database (Denmark)

    Lundgren, Jens; Emery, Sean; Neuhaus, Jacqueline A

    2008-01-01

    BACKGROUND: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group......, participants started ART when the CD4+ cell count was ART at entry inform the early use of ART. METHODS: Patients who were either ART naive (n=249) or who had not been receiving ART for >or= 6 months (n=228) were analyzed. The following......). RESULTS: A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4...

  15. Short term clinical disease progression in HIV-1 positive patients taking combination antiretroviral therapy : The EuroSIDA risk-score

    DEFF Research Database (Denmark)

    Mocroft, A; Ledergerber, B; Zilmer, K

    2007-01-01

    /death in patients taking cART. A score was derived for 4169 patients from EuroSIDA and validated on 5150 patients from the Swiss HIV Cohort Study (SHCS). RESULTS: In EuroSIDA, 658 events occurred during 22 321 person-years of follow-up: an incidence rate of 3.0/100 person-years of follow-up [95% confidence interval...... (CI), 2.7-3.3]. Current levels of viral load, CD4 cell count, CD4 cell slope, anaemia, and body mass index all independently predicted new AIDS/death, as did age, exposure group, a prior AIDS diagnosis, prior antiretroviral treatment and stopping all antiretroviral drugs. The EuroSIDA risk...... in the risk-score was associated with a 2.70 times higher incidence of clinical progression (95% CI, 2.56-2.84) in EuroSIDA and 2.88 (95% CI, 2.75-3.02) in SHCS. CONCLUSIONS: A clinically relevant prognostic score was derived in EuroSIDA and validated within the SHCS, with good agreement. The EuroSIDA risk...

  16. Evolution of HVR-1 quasispecies after 1-year treatment in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy.

    Science.gov (United States)

    Solmone, Mariacarmela; Girardi, Enrico; Lalle, Eleonora; Abbate, Isabella; D'Arminio Monforte, Antonella; Cozzi-Lepri, Alessandro; Alessandrini, Anna; Piscopo, Rita; Ebo, Francesca; Cosco, Lucio; Antonucci, Giorgio; Ippolito, Giuseppe; Capobianchi, Maria R

    2006-01-01

    Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+ T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological nonresponders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load HVR-1 region of HCV. Nonsynonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.

  17. Nurse led, primary care based antiretroviral treatment versus hospital care: a controlled prospective study in Swaziland

    Directory of Open Access Journals (Sweden)

    Bailey Kerry A

    2010-08-01

    Full Text Available Abstract Background Antiretroviral treatment services delivered in hospital settings in Africa increasingly lack capacity to meet demand and are difficult to access by patients. We evaluate the effectiveness of nurse led primary care based antiretroviral treatment by comparison with usual hospital care in a typical rural sub Saharan African setting. Methods We undertook a prospective, controlled evaluation of planned service change in Lubombo, Swaziland. Clinically stable adults with a CD4 count > 100 and on antiretroviral treatment for at least four weeks at the district hospital were assigned to either nurse led primary care based antiretroviral treatment care or usual hospital care. Assignment depended on the location of the nearest primary care clinic. The main outcome measures were clinic attendance and patient experience. Results Those receiving primary care based treatment were less likely to miss an appointment compared with those continuing to receive hospital care (RR 0·37, p p = 0·001. Those receiving primary care based, nurse led care were more likely to be satisfied in the ability of staff to manage their condition (RR 1·23, p = 0·003. There was no significant difference in loss to follow-up or other health related outcomes in modified intention to treat analysis. Multilevel, multivariable regression identified little inter-cluster variation. Conclusions Clinic attendance and patient experience are better with nurse led primary care based antiretroviral treatment care than with hospital care; health related outcomes appear equally good. This evidence supports efforts of the WHO to scale-up universal access to antiretroviral treatment in sub Saharan Africa.

  18. Do HIV care providers appropriately manage hepatitis B in coinfected patients treated with antiretroviral therapy?

    Science.gov (United States)

    Jain, Mamta K; Opio, Christopher K; Osuagwu, Chukwuma C; Pillai, Rathi; Keiser, Philip; Lee, William M

    2007-04-01

    The common occurrence of hepatitis B virus (HBV) infection in patients who carry the human immunodeficiency virus (HIV) demands that both viruses be recognized, evaluated, and treated when appropriate. We identified 357 HIV- and hepatitis B surface antigen-positive patients who underwent testing from 1999 to 2003; 155 patients who were new to our clinic and who initiated therapy for HIV and HBV coinfection were considered for inclusion in the study. The frequency of HIV testing (to determine HIV load and CD4+ cell count) performed during the first year of therapy was compared with the frequency of HBV measurements (to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load), abdominal ultrasound examination, and measurement of levels of alpha-fetoprotein in serum. HBV load data were obtained for only 16% of patients before initiation of antiretroviral therapy (ART), whereas HIV load was determined for 99% of patients before initiation of ART. The total number of HIV load measurements obtained during the first year after ART initiation was 497 (median number of HIV load measurements per patient, 3.0), compared with 85 measurements of HBV load (median number of HBV load measurements per patient, <1; P<.001). The percentage of patients who received any level of HBV monitoring (i.e., tests to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load) after ART initiation increased from 7% in 1999 to 52% in 2001 (P<.001), whereas the percentage of patients who underwent HIV load testing remained at 80%-90% during the same period. Health care providers treating patients with HIV infection during the period 1999-2003 infrequently monitored HBV response in coinfected patients, but they systematically monitored HIV response after ART initiation. Improved physician adherence to guidelines that better delineate HBV treatment and monitoring for patients with HIV-HBV coinfection is needed.

  19. Outcomes of human immunodeficiency virus-infected children after anti-retroviral therapy in Malaysia.

    Science.gov (United States)

    Moy, Fong Siew; Fahey, Paul; Nik Yusoff, Nik K; Razali, Kamarul A; Nallusamy, Revathy

    2015-02-01

    To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART). Retrospective and prospective data collected through March 2009 from children in four different states in Malaysia enrolled in TREAT Asia's Pediatric HIV Observational Database were analysed. Of 347 children in the cohort, only 278 (80.1%) were commenced on ART. The median CD4 count and median age at baseline prior to ART was 272 cells/μL and 4.2 years (interquartile range (IQR): 1.4, 7.4 years), respectively. The median duration of follow-up was 3.7 years (IQR: 1.8, 6.0) with 32 deaths giving a crude mortality rate of 2.86 per 100 child-years. The mortality rate highest in the first 6 months of ART was 10.62 per 100 child-years and declined to 1.83 per 100 child-years thereafter. On univariate analyses, only baseline median CD4 percentage, weight for age z score, height for age z score and anaemia were significantly associated with mortality. Upon including all four of these predictors into a single multivariate model, only weight for age z score remained statistically significantly predictive of mortality. Children commenced on ART had high mortality in the first 6 months especially in those with low CD4 percentage, wasting and anaemia. Poor nutritional status is an important independent predictor of mortality in this study. Besides initiating ART therapy, nutritional support and intervention must receive the utmost attention. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  20. Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

    Science.gov (United States)

    Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

    2012-01-01

    Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

  1. Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    Petropoulos Christos J

    2005-11-01

    Full Text Available Abstract Background Central nervous system (CNS exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1 progression of systemic infection, 2 CSF white blood cell (WBC count, 3 antiretroviral therapy (ART, and 4 neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL. CSF HIV viral loads (VLs correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

  2. HIV cure strategies: how good must they be to improve on current antiretroviral therapy?

    Directory of Open Access Journals (Sweden)

    Paul E Sax

    Full Text Available We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART.We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT, each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY.For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving.Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.

  3. Sex Differences in the Incidence of Peripheral Neuropathy Among Kenyans Initiating Antiretroviral Therapy

    Science.gov (United States)

    Ahmed, Aabid; Laverty, Maura; Holzman, Robert S.; Valentine, Fred; Sivapalasingam, Sumathi

    2011-01-01

    Background. Peripheral neuropathy (PN) is common among patients receiving antiretroviral therapy (ART) in resource-limited settings. We report the incidence of and risk factors for PN among human immunodeficiency virus (HIV)–infected Kenyan adults initiating ART. Methods. An inception cohort was formed of adults initiating ART. They were screened for PN at baseline and every 3 months for 1 year. We used the validated Brief Peripheral Neuropathy Screen (BPNS) that includes symptoms and signs (vibration perception and ankle reflexes) of PN. Results. Twenty-two (11%) of 199 patients had PN at baseline screening. One hundred fifty patients without evidence of PN at baseline were followed for a median of 366 days (interquartile range, 351–399). The incidence of PN was 11.9 per 100 person-years (95% confidence interval [CI], 6.9–19.1) and was higher in women than men (17.7 vs 1.9 per 100 person-years; rate ratio, 9.6; 95% CI, 1.27–72, P = .03). In stratified analyses, female sex remained statistically significant after adjustment for each of the following variables: age, CD4 cell count, body mass index, ART regimen, and tuberculosis treatment. Stratifying hemoglobin levels decreased the hazard ratio from 9.6 to 7.40 (P = .05), with higher levels corresponding to a lower risk of PN. Conclusions. HIV-infected Kenyan women were almost 10 times more likely than men to develop PN in the first year of ART. The risk decreased slightly at higher hemoglobin levels. Preventing or treating anemia in women before ART initiation and implementing BPNS during the first year of ART, the period of highest risk, could ameliorate the risk of PN. PMID:21844033

  4. Depression and posttraumatic stress disorder among HIV-infected Gambians on antiretroviral therapy.

    Science.gov (United States)

    Peterson, Kevin; Togun, Toyin; Klis, Sandor; Menten, Joris; Colebunders, Robert

    2012-10-01

    Mood disorders are more frequent among people with HIV infection than among non-HIV-infected individuals of the same age, socioeconomic status, and HIV risks. They have been associated with worse adherence and clinical outcomes, yet remain underdiagnosed and undertreated in sub-Saharan Africa. We explored the relationship between mood disorders using the 10-item depression scale of the Centers for Epidemiological Studies (CES-D10) and the 22-item Impact of Events Scale-Revised (IES-R) for posttraumatic stress disorder, and a range of demographic and HIV-related variables among 252 consecutive subjects on antiretroviral therapy (ART). The study was conducted in the Genito-Urinary Medicine Clinic of the Medical Research Council's Gambia Unit. These screening tests were positive in 7% and 30%, respectively, of the patients, with higher scores (more depression or more post-traumatic stress) associated with female gender, more advanced WHO clinical stage, and lower Karnofsky Perfomance Scale rating. Higher CES-D10 scores were also seen among those on their second ART regimen. No relationship was seen with age, time on ART, viral load, or CD4 cell count. Compared to an earlier study at the same site in subjects prior to starting ART, the prevalence of depression in those stabilized on ART was dramatically reduced (by 34%, from 41%) while that of PTSD dropped less (by 13%, from 43%). Integrating the CES-D10 or a similar instrument into patient preparation for ART is recommended in order to identify those who may benefit from further mental health investigations, specific therapy, or closer follow-up during early ART.

  5. Mortality among people living with HIV on antiretroviral treatment in Bali, Indonesia: incidence and predictors.

    Science.gov (United States)

    Utami, Sri; Sawitri, Anak Agung Sagung; Wulandari, Luh Putu Lila; Artawan Eka Putra, I Wayan Gede; Astuti, Putu Ayu Swandewi; Wirawan, Dewa Nyoman; Causer, Louise; Mathers, Bradley

    2017-10-01

    Indonesia has the third highest number of people living with HIV/AIDS (PLWH) and the greatest increase in proportion of AIDS-related mortality in the Asia Pacific region between 2005 and 2013. Longitudinal mortality data among PLWH in Indonesia are limited. We conducted a retrospective cohort study from medical records of antiretroviral treatment (ART) recipients attending Badung General Hospital (BGH) and Bali Medica Clinic (BMC) between 2006 and 2014. We explored incidence of mortality by Kaplan-Meier analysis and identified predictors using a Cox proportional hazard model. In total, 575 patients were included in the analysis; the majority were male. The overall mortality rate was 10% per year. Multivariate analysis suggested that being male (adjusted hazard ratio [aHR]: 2.74; 95% confidence interval [CI]: 1.34-5.59), having a lower education (aHR: 2.17; 95%CI: 1.31-3.61), having heterosexual (aHR: 7.40; 95% CI: 2.61-21.00) or injecting drug use (aHR: 13.20; 95% CI: 3.17-55.00) as the likely transmission risk category, starting treatment with low CD4 cell counts (aHR: 3.18; 95% CI: 1.16-8.69), and not having a treatment supervisor (aHR: 4.02; 95% CI: 2.44-6.65) were independent predictors of mortality. The mortality was high, particularly in the first three months after initiating ART. These findings highlight the need to encourage HIV testing and early diagnosis and prompt treatment. Applying aspects of BMCs targeted HIV services model in more generalised services such as BGH may be beneficial. Providing adherence support as part of ART services is key to promoting adherence to ART.

  6. Self-reported adherence to antiretroviral therapy in HIV+ population from Bata, Equatorial Guinea.

    Science.gov (United States)

    Salmanton-García, Jon; Herrador, Zaida; Ruiz-Seco, Pilar; Nzang-Esono, Jesús; Bendomo, Veronica; Bashmakovic, Emma; Nseng-Nchama, Gloria; Benito, Agustín; Aparicio, Pilar

    2016-01-01

    The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives.

  7. Responsibility and expectations in antiretroviral therapy--patients' versus doctors' perspective.

    Science.gov (United States)

    Largu, Maria Alexandra; Dorobăţ, Carmen; Oprea, L; Astărăstoae, V; Manciuc, Carmen

    2015-01-01

    This paper aims to uncover what patients really expect form ART, and also what infectious diseases doctors expect from a patient's ART regime, thus exploring an important side of adherence to ART. From July to November 2014 we have conducted a qualitative study regarding both patients' and doctors' expectations form the ART. We interviewed 30 patients and 4 doctors. We used semi-structured interviews that were conducted in the Psychosocial Compartment of the HIV/AIDS Regional Center in Iasi. The patients we interviewed came from all 6 counties in the Moldova area. Age varied from 16 years to 59 years; 55% were female and 45% male. 30% came from a rural area. The most common expectations that patients have regarding ART are: "to help me live", "not to make me feel sick", "to be easy to take (not to big, not a lot)", "not to show on the outside what I have on the inside". The infectious diseases doctors that we interviewed work in the HIV/AIDS Regional Center in Iasi. Their expectations regarding an ART regimen for patients were: "to reduce HIV viral load", "to increase CD4 cell count" and "to have minimal impact on the proper functioning of other organs". Patients consider themselves the only factors responsible for their own ART adherence in 56.6% of cases; 20% consider the doctor to be responsible for their adherence, 16.6% feel that their family, friends, and spouse are responsible, and 6.6% (2 patients) couldn't answer. Infectious diseases doctors considered that patients are 100% responsible for adhering to the antiretroviral therapy. In order to assure adherence to the ART it is important to explore both the doctor and the patient's perspective and to find ways to find a common ground in building a healthy relationship.

  8. Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Ana Cecília Montes Gil

    Full Text Available CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART. We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6, A (29, B (78 and C (39. Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN, grade 2 (5.0-9.9 times ULN, grade 3 (10.0-15.0 times ULN and grade 4 (> 15.0 times ULN. To assess hepatotoxicity risk factors, odds ratios (OR and adjusted odds ratios (aOR for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152 patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI, 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85 and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25. No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

  9. Comparison of anti-retroviral therapy treatment strategies in prevention of mother-to-child transmission in a teaching hospital in Ethiopia.

    Science.gov (United States)

    Kumela, Kabaye; Amenu, Demisew; Chelkeba, Legese

    2015-01-01

    than 350 cells/cubic mm (OR=6.98, 95%CI=0.91-53.76), early infant infection (OR=5.4, 95%CI=2.04-14.4), infants delivered home (OR=13.1, 95%CI=2.69-63.7), infant with birth weight less than 2500 g (OR=6.41, 95%CI=2.21-18.61), and mixed infant feeding (OR=6.7, 95%CI=2.2-20.4). Antiretroviral regimen duration less than 2 months, maternal base line CD4 less than 350 cells/cubic mm and mixed infant feeding were also important risk factors for late infant infection or death. The effectiveness of multiple antiretroviral drugs in prevention of early mother-to-child transmission of HIV was found to be more effective than that of single dose nevirapine, although, the difference was not statistically significant. But in late transmission, a significant difference was observed in which infants born to mother who received multiple antiretroviral drugs were less likely to progress to infection or death than infants born to mothers who received single dose nevirapine.

  10. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

    2015-01-01

    ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

  11. Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy

    Science.gov (United States)

    Solomon, Ajantha; Ghneim, Khader; Ahlers, Jeffrey; Cameron, Mark J.; Smith, Miranda Z.; Spelman, Tim; McMahon, James; Velayudham, Pushparaj; Brown, Gregor; Roney, Janine; Watson, Jo; Prince, Miles H.; Hoy, Jennifer F.; Chomont, Nicolas; Fromentin, Rémi; Procopio, Francesco A.; Zeidan, Joumana; Palmer, Sarah; Odevall, Lina; Johnstone, Ricky W.; Martin, Ben P.; Sinclair, Elizabeth; Deeks, Steven G.; Hazuda, Daria J.; Cameron, Paul U.; Sékaly, Rafick-Pierre; Lewin, Sharon R.

    2014-01-01

    Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells. Trial Registration ClinicalTrials.gov NCT01365065 PMID:25393648

  12. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Julian H Elliott

    2014-10-01

    Full Text Available Human immunodeficiency virus (HIV persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART. The primary endpoint was change in cell associated unspliced (CA-US HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065. Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90% with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1. CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.ClinicalTrials.gov NCT01365065.

  13. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Mónica Rodríguez

    2012-01-01

    Full Text Available We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes.

  14. Implementing antiretroviral therapy programs in resource-constrained settings: lessons from Monze, Zambia.

    Science.gov (United States)

    Adedimeji, Adebola; Malokota, Oliver; Manafa, Ogenna

    2011-05-01

    We describe the impact of an antiretroviral therapy program on human resource utilization and service delivery in a rural hospital in Monze, Zambia, using qualitative data. We assess project impact on staff capacity utilization, service delivery, and community perception of care. Increased workload resulted in fatigue, low staff morale, and exacerbated critical manpower shortages, but also an increase in users of antiretroviral therapy, improvement in hospital infrastructure and funding, and an overall community satisfaction with service delivery. Integrating HAART programs within existing hospital units and services may be a good alternative to increase overall efficiency.

  15. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS.......026) and time (P changes were observed (south, P = 0.061; central west, P ....001; north: P = 0.070; east, P = 0.001). CONCLUSIONS: There was some evidence of regional differences in initial virologic response to cART. Improvements over time were observed, suggesting that so far, the effect of primary resistance has not been of sufficient magnitude to prevent increasing suppression...

  16. Impact of switching antiretroviral therapy on lipodystrophy and other metabolic complications: a review

    DEFF Research Database (Denmark)

    Hansen, Birgitte R; Haugaard, Steen B; Iversen, Johan

    2004-01-01

    Following the introduction of highly active antiretroviral therapy (HAART), metabolic and morphological complications known as HIV associated lipodystrophy syndrome (HALS) have been increasingly common. The approaches to target these complications span from resistance exercise, diet and use...... of the antidiabetics metformin or glitazones to high dose recombinant human growth hormone therapy or switching antiretroviral regimen. When looking at the effect of switching therapy, focus has been addressed to protease inhibitor (PI) based regimens, as PI was the first component of HAART recognized to be correlated...

  17. Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Salgado Maria

    2011-12-01

    Full Text Available Abstract Background While initiation of highly active antiretroviral therapy (HAART during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Results Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of + T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+ T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+ T cells do not have potent HIV suppressive activity. Conclusion This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL mediated suppression that has been reported in many elite suppressors.

  18. Scaling up antiretroviral treatment services in Karnataka, India: impact on CD4 counts of HIV-infected people.

    Directory of Open Access Journals (Sweden)

    Suresh Shastri

    Full Text Available SETTING: Twelve antiretroviral treatment centres under National AIDS Control Programme (NACP, Karnataka State, India. OBJECTIVE: For the period 2004-2011, to describe the trends in the numbers of people living with HIV (PLHIV registered for care and their median baseline CD4 counts, disaggregated by age and sex. DESIGN: Descriptive study involving analysis of routinely captured data (year of registration, age, sex, baseline CD4 count under NACP. RESULTS: 34,882 (97% of total eligible PLHIV were included in analysis. The number registered for care has increased by over 12 times during 2004-11; with increasing numbers among females. The median baseline CD4 cell count rose from 125 in 2004 to 235 in 2011--the increase was greater among females as compared to males. However, about two-thirds still presented at CD4 cell counts less than 350. CONCLUSION: We found an increasing trend of median CD4 counts among PLHIV presenting to ART centres in Karnataka, an indicator of enhanced and early access to HIV care. Equal proportion of females and higher baseline CD4 counts among them allays any fear of differential access by gender. Despite this relative success, a substantial proportion still presented at low CD4 cell counts indicating possibly delayed HIV diagnosis and delayed linkage to HIV care. Universal HIV testing at health care facilities and strengthening early access to care are required to bridge the gap.

  19. Adjuvant potential of virgin coconut oil extract on antiretroviral therapy-induced testicular toxicity: An ultrastructural study.

    Science.gov (United States)

    Ogedengbe, O O; Jegede, A I; Onanuga, I O; Offor, U; Peter, A I; Akang, E N; Naidu, E C S; Azu, O O

    2018-04-01

    The effects of Virgin coconut oil as an adjuvant to highly active antiretroviral therapy (HAART) were investigated on the testicular ultrastructure and biochemical markers in rats. Twenty male Sprague-Dawley rats, weighing 153-169 g were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (HAART+Virgin coconut oil 10 ml/kg) and D (Virgin coconut oil [VCO] 10 ml/kg). Testicular segments were evaluated using transmission electron microscopy. Serum was assayed for testosterone, luteinising hormone, follicle stimulating hormone and testicular tissue for malondialdehyde and glutathione. Ultrastructure of basement membrane (Bm), mitochondria and spermatocytes was normal in the control group. HAART-treated group showed significant increase (p group. Mitochondrial cristae appear collapsed, and Sertoli cells showed cytoplasmic vacuolations. HAART+VCO group showed improved ultrastructural details in Bm, and Sertoli cell and Leydig cells show abundant lipid droplets. Virgin coconut oil-treated group showed thinning of Bm with otherwise normal ultrastructural features of organelles. HAART-treated group showed significant increase (p Virgin coconut oil improved testicular morphology and reversed HAART-induced ultrastructural alterations. Further studies on putative mechanism are required. © 2017 Blackwell Verlag GmbH.

  20. Perception of antiretroviral generic medicines: one-day survey of HIV-infected patients and their physicians in France.

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    Christine Jacomet

    Full Text Available In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians.556 out of 703 (79% adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (p<0.001. Among the 116 physicians following a median of 100 HIV-patients/year, 75% would prescribe generics, dropping to 26% if the combo had to be broken. Factors significantly associated with willingness to prescribe antiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33, being aware that the patient would accept generics for other pathologies (OR = 2.04 and would accept antiretroviral generics (OR = 1.94. No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics.Acceptability of antiretroviral generics in this French population was mostly dictated by the patient's and physician's knowledge and use of generics overall. It should be improved

  1. Determinants of Optimal Adherence to Antiretroviral Therapy among ...

    African Journals Online (AJOL)

    SITWALA COMPUTERS

    medication side effects and adolescence were associated with non-adherence (p ... especially the social determinants of health surrounding ... irrespective of their CD4 cell count. ..... reported were cell phone alarm, radio news hour time, or a.

  2. Predictors of change in CD4 lymphocyte count and weight among HIV infected patients on anti-retroviral treatment in Ethiopia: a retrospective longitudinal study.

    Directory of Open Access Journals (Sweden)

    Ayalu A Reda

    Full Text Available Antiretroviral treatment (ART has been introduced in Ethiopia a decade ago and continues to be scaled up. However, there is dearth of literature on the impact of ART on changes in CD4 lymphocyte count and weight among patients on treatment.To determine the predictors of change in CD4 lymphocyte count and weight among HIV/AIDS infected patients taking antiretroviral treatment in eastern Ethiopia.A retrospective cohort study was conducted among HIV/AIDS patients taking ART from 2005 to 2010. A sample of 1540 HIV infected adult patients who started antiretroviral therapy in hospitals located in eastern Ethiopia were included in the study. The primary outcomes of interest were changes in CD4 count and weight. Descriptive statistics and multivariable regression analyses were performed to examine the outcomes among the cohort.Both the median CD4 lymphocyte counts and weight showed improvements in the follow up periods. The multivariate analysis shows that the duration of ART was an important predictor of improvements in CD4 lymphocyte count (beta 7.91; 95% CI 7.48-8.34; p 0.000 and weight (beta 0.15; 95% CI 0.13-0.18; p 0.000. Advanced WHO clinical stage, lower baseline CD4 cell count, and baseline hemoglobin levels were factors associated with decline in weight. Actively working patients had higher CD4 lymphocyte count and weight compared to those that were ambulatory (p<0.05.We detected a substantial increment in weight and CD4 lymphocyte count among the patients who were taking ART in eastern Ethiopia. Patients who are of older age, with low initial CD4 lymphocyte count, late stage of the WHO clinical stages and lower hemoglobin level may need special attention. The reasons for the improved findings on CD4 count and weight throughout the five years of follow up merit further investigation.

  3. Clinical differences between younger and older adults with HIV/AIDS starting antiretroviral therapy in Uganda and Zimbabwe: a secondary analysis of the DART trial.

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    Sujal M Parikh

    Full Text Available Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low-income African countries.HIV clinics in Uganda and Zimbabwe.Secondary exploratory cross-sectional analysis of the DART randomized controlled trial.Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger and ≥ 50 years (older, using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART and one without.A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7% were ≥ 50 years and 1160 (35% were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important higher CD4+ cell counts and higher plasma HIV-1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis.Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy.

  4. Prevalence, correlates and under-diagnosis of clinical depression among adults on highly active antiretroviral therapy in a Tertiary Health Institution in northeastern Nigeria

    Directory of Open Access Journals (Sweden)

    Abdu Wakawa Ibrahim

    2014-11-01

    Full Text Available Clinical depression is a highly debilitating illness, which is often under-diagnosed and negatively impacts on the quality of life of its sufferers. When it co-exists with other medical conditions, its effect is even more incapacitating. Undiagnosed depression in the context of HIV infection leads to accelerated decline in CD4+ cell counts with concomitant increase in the viral load and poor adherence to the antiretroviral medications which lead to viral mutation and the evolution of resistant strains. This study examined the prevalence of depression, its correlates and the frequency of the diagnosis of the condition among HIV+ subjects on highly active antiretroviral therapy (HAART by the internists and general physicians at the University of Maiduguri Teaching Hospital in Northeastern Nigeria. Three hundred and fifty representative samples of HIV+ adults on HAART were drawn from the Antiretroviral Therapy Clinic of the Institution. Diagnosis of depression was made using the International Classification of Diseases-10 criteria based on Composite International Diagnostic Interview generated data. Socio-demographic and clinical variables were also analyzed for their correlation with depression in the subjects. About 20% of the respondents were diagnosed with clinical depression and no diagnosis of the condition was hitherto entertained in all the respondents. The independent determinants of depression in the participants were: female gender [odds ratio (OR=3.87 (95% confidence interval, CI: 2.089-7.183], past history of psychiatric illness [OR=43.81 (95% CI: 9.731-197.30] and family history of psychiatric illness in first-degree relatives of the subjects [OR=14.364 (95% CI=5.327- 38.729]. Depression is a relatively common psychiatric condition among adults on HAART, there is therefore the need for routine screening of this condition among HIV+ subjects in order to optimize patient care and improve clinical outcomes.

  5. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    DEFF Research Database (Denmark)

    NN, NN; Mugavero, Michael J; May, Margaret

    2008-01-01

    , nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation.......58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1......OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between...

  6. Effects of HIV-1 protease on cellular functions and their potential applications in antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Yang Hailiu

    2012-09-01

    Full Text Available Abstract Human Immunodeficiency Virus Type 1 (HIV-1 protease inhibitors (PIs are the most potent class of drugs in antiretroviral therapies. However, viral drug resistance to PIs could emerge rapidly thus reducing the effectiveness of those drugs. Of note, all current FDA-approved PIs are competitive inhibitors, i.e., inhibitors that compete with substrates for the active enzymatic site. This common inhibitory approach increases the likelihood of developing drug resistant HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that move away from the current target of the active enzymatic site are needed. Specifically, allosteric inhibitors, inhibitors that prohibit PR enzymatic activities through non-competitive binding to PR, should be sought. Another common feature of current PIs is they were all developed based on the structure-based design. Drugs derived from a structure-based strategy may generate target specific and potent inhibitors. However, this type of drug design can only target one site at a time and drugs discovered by this method are often associated with strong side effects such as cellular toxicity, limiting its number of target choices, efficacy, and applicability. In contrast, a cell-based system may provide a useful alternative strategy that can overcome many of the inherited shortcomings associated with structure-based drug designs. For example, allosteric PIs can be sought using a cell-based system without considering the site or mechanism of inhibition. In addition, a cell-based system can eliminate those PIs that have strong cytotoxic effect. Most importantly, a simple, economical, and easy-to-maintained eukaryotic cellular system such as yeast will allow us to search for potential PIs in a large-scaled high throughput screening (HTS system, thus increasing the chances of success. Based on our many years of experience in using fission yeast as a model system to study HIV-1 Vpr, we propose the use of

  7. The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

    Science.gov (United States)

    Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

    2017-11-15

    The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  8. Accessibility of antiretroviral therapy in Ghana: convenience of access.

    Science.gov (United States)

    Addo-Atuah, Joyce; Gourley, Dick; Gourley, Greta; White-Means, Shelley I; Womeodu, Robin J; Faris, Richard J; Addo, Nii Akwei

    2012-01-01

    The convenience of accessing antiretroviral therapy (ART) is important for initial access to care and subsequent adherence to ART. We conducted a qualitative study of people living with HIV/AIDS (PLWHA) and ART healthcare providers in Ghana in 2005. The objective of this study was to explore the participants' perceived convenience of accessing ART by PLWHA in Ghana. The convenience of accessing ART was evaluated from the reported travel and waiting times to receive care, the availability, or otherwise, of special considerations, with respect to the waiting time to receive care, for those PLWHA who were in active employment in the formal sector, the frequency of clinic visits before and after initiating ART, and whether the PLWHA saw the same or different providers at each clinic visit (continuity of care). This qualitative study used in-depth interviews based on Yin's case-study research design to collect data from 20 PLWHA and 24 ART healthcare providers as study participants. • Reported travel time to receive ART services ranged from 2 to 12 h for 30% of the PLWHA. • Waiting time to receive care was from 4 to 9 h. • While known government workers, such as teachers, were attended to earlier in some of the centres, this was not a consistent practice in all the four ART centres studied. • The PLWHA corroborated the providers' description of the procedure for initiating and monitoring ART in Ghana. • PLWHA did not see the same provider every time, but they were assured that this did not compromise the continuity of their care. Our study suggests that convenience of accessing ART is important to both PLWHA and ART healthcare providers, but the participants alluded to other factors, including open provider-patient communication, which might explain the PLWHA's understanding of the constraints under which they were receiving care. The current nation-wide coverage of the ART programme in Ghana, however, calls for the replication of this study to identify

  9. Perceived stigma by children on antiretroviral treatment in Cambodia.

    Science.gov (United States)

    Barennes, Hubert; Tat, Sovann; Reinharz, Daniel; Vibol, Ung

    2014-12-10

    HIV-related stigma diminishes the quality of life of affected patients. Little is known about perceived and enacted stigma of HIV-infected children in resources-limited settings. We documented the prevalence of perceived stigma and associated factors associated among children on antiretroviral therapy (ART) at a referral hospital in Cambodia. After informed consent, a standardized pre-tested 47-item questionnaire was confidentially administered to consecutive children (7 to 15 years) or their guardians if the child was 18 months to 6 years, during their routine ART visits. The questionnaire explored the sociodemographics of the child and the parents, HIV history, adherence to ART, tolerance of ART and perceived stigma. Associations between perceived stigma and the children's characteristics were measured by bivariate and multivariate analyses. Of 183 children, 101 (55.2%) had lost at least one and 45 (24.6%) both parents; 166 (90.7%) went to school. Of 183 children (female: 84, 45.9%, median age 7.0 years, interquartile range: 2.0-9.6), 79 (43.2%) experienced perceived stigma, including rejection by others (26.8%), no invitations to social activities (18.6%) and exclusion from games (14.2%). A total of 43 (23.5%) children were fearful of their disease and 61 (53.9%) of 113 older than 6 years reported knowledge of their HIV status. Of 136 children over five years and eligible for education, 7 (3.8%) could not go to school due to perceived stigma. Incomplete adherence to ART was reported for 17 (9.2%) children. In multivariate analysis, school attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.0-7.9) and income of less than one dollar per person per day (OR: 2.2, 95% CI: 1.1-4.5) were associated with perceived stigma. Conversely, receipt of social support (OR: 0.4, 95% CI 0.2-0.9) was associated with lower risk of perceived stigma. Perceived stigma in pediatric ART patients remains a significant issue in Cambodia. Psychological support and

  10. Factors associated with suboptimal adherence to antiretroviral therapy in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Kumarasamy, Nagalingeswaran; Ditangco, Rossana; Li, Patrick CK; Phanuphak, Praphan; Sirisanthana, Thira; Sungkanuparph, Somnuek; Kantipong, Pacharee; Lee, Christopher KC; Mustafa, Mahiran; Merati, Tuti; Kamarulzaman, Adeeba; Singtoroj, Thida; Law, Matthew

    2014-01-01

    Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) 14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported 2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social

  11. Designing equitable antiretroviral allocation strategies in resource-constrained countries.

    Directory of Open Access Journals (Sweden)

    David P Wilson

    2005-02-01

    Full Text Available Recently, a global commitment has been made to expand access to antiretrovirals (ARVs in the developing world. However, in many resource-constrained countries the number of individuals infected with HIV in need of treatment will far exceed the supply of ARVs, and only a limited number of health-care facilities (HCFs will be available for ARV distribution. Deciding how to allocate the limited supply of ARVs among HCFs will be extremely difficult. Resource allocation decisions can be made on the basis of many epidemiological, ethical, or preferential treatment priority criteria.Here we use operations research techniques, and we show how to determine the optimal strategy for allocating ARVs among HCFs in order to satisfy the equitable criterion that each individual infected with HIV has an equal chance of receiving ARVs. We present a novel spatial mathematical model that includes heterogeneity in treatment accessibility. We show how to use our theoretical framework, in conjunction with an equity objective function, to determine an optimal equitable allocation strategy (OEAS for ARVs in resource-constrained regions. Our equity objective function enables us to apply the egalitarian principle of equity with respect to access to health care. We use data from the detailed ARV rollout plan designed by the government of South Africa to determine an OEAS for the province of KwaZulu-Natal. We determine the OEAS for KwaZulu-Natal, and we then compare this OEAS with two other ARV allocation strategies: (i allocating ARVs only to Durban (the largest urban city in KwaZulu-Natal province and (ii allocating ARVs equally to all available HCFs. In addition, we compare the OEAS to the current allocation plan of the South African government (which is based upon allocating ARVs to 17 HCFs. We show that our OEAS significantly improves equity in treatment accessibility in comparison with these three ARV allocation strategies. We also quantify how the size of the

  12. Fixed-dose combination for adults accessing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    SA HIV Clinicians Society

    2013-02-01

    Full Text Available This document serves to guide clinicians and programme managers on how to switch from 3 separate antiretroviral (ARV drugs to the new, single, fixed-dose combination (FDC tablet containing tenofovir (TDF, emtricitabine (FTC and efavirenz (EFV. Summary Transitioning from individual drugs to an FDC tablet needs to be managed carefully, particularly regarding stock management, ordering processes, supply-chain integrity and comprehensive patient counselling. Priority groups • Initially, FDC supply will be insufficient to provide for all FDC-suitable patients • Therefore, the National Department of Health (NDoH has recommended that the following patient groups be prioritized for FDC initiation/switch: • Priority group 1: All HIV-positive patients newly initiating ART – adults, adolescents and pregnant women (regardless of CD4 count (amendment to the guidelines for the prevention of mother-to-child transmission of HIV (PMTCT anticipated in April 2013 – and who do not have contra-indications to the FDC component drugs • Priority group 2: HIV-positive pregnant women and breastfeeding mothers currently stable on lamivudine (3TC, TDF and EFV • Priority group 3: Virologically suppressed patients on a stavudine (d4T-based regimen and who have normal renal function • Priority group 4: Stable patients receiving individual TDF, 3TC and EFV and who have tuberculosis (TB co-infection • Priority group 5: Stable patients receiving individual TDF, 3TC and EFV and who have other co-morbidites (e.g. hypertension, diabetes • Priority group 6: Patients receiving individual TDF, 3TC and EFV and who request to switch to the FDC treatment • Priority group 7: Patients receiving individual TDF, 3TC and EFV and who, after counselling, agree to switch to the FDC treatment. Important: Clinic staff must co-ordinate this process and only switch as many patients to the FDC tablet as stock allows. This should avoid patients being switched back and forth

  13. Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection.

    Science.gov (United States)

    Kader, M; Bixler, S; Piatak, M; Lifson, J; Mattapallil, J J

    2009-10-01

    Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th-17 cells (IL-17(+)CD4(+) T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to repopulation of CD4(+) T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th-17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th-17 cells that are lost during infection. Dynamics of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th-17 and Tc-17 cells was determined following infection and after therapy. Relative expression of IL-21, IL-23, and TGFbeta was determined using Taqman PCR. Treatment of SIV infected rhesus macaques with anti-retroviral therapy was associated with a substantial repopulation of mucosal homing alpha4(+)beta7(hi)CD4(+) T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th-17 responses. Interestingly, SIV infection was associated with an increase in Tc-17 responses (IL-17(+)CD8(+) T cells) suggesting to a skewing in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th-17 : Tc-17 responses induced following SIV infection. ART was associated with substantial repopulation of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood with little or no rebound of Th-17 cells. On the other hand, repopulation of alpha4(+)beta7(hi) CD4(+) T cells was accompanied by persistence of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17

  14. Directly administered antiretroviral therapy for HIV-infected drug users does not have an impact on antiretroviral resistance: results from a randomized controlled trial.

    Science.gov (United States)

    Maru, Duncan Smith-Rohrberg; Kozal, Michael J; Bruce, R Douglas; Springer, Sandra A; Altice, Frederick L

    2007-12-15

    Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.

  15. Highly specific reasons for nonadherence to antiretroviral therapy: results from the German adherence study

    Directory of Open Access Journals (Sweden)

    Boretzki J

    2017-11-01

    Full Text Available Johanna Boretzki,1,2 Eva Wolf,3 Carmen Wiese,4 Sebastian Noe,4 Annamaria Balogh,3 Anja Meurer,5 Ivanka Krznaric,6 Alexander Zink,7 Christian Lersch,1 Christoph D Spinner1,2 1Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, 2German Center for Infection Research, Partner Site Munich, 3MUC Research, Munich, 4MVZ Karlsplatz, HIV Clinical Care Center, Munich, 5Center for Infectiology and Internal Medicine, Munich, 6Center for Infectiology Prenzlauer Berg, Berlin, 7Department of Dermatology and Allergology, University Hospital Klinikum rechts der Isar, Munich, Germany Background: Reasons for and frequency of nonadherence to antiretroviral therapy (ART may have changed due to pharmacological improvements. In addition, the importance of known non-pharmacologic reasons for nonadherence is unclear.Methods: We performed a cross-sectional, noninterventional, multicenter study to identify current reasons for nonadherence. Patients were categorized by physicians into the following adherence groups: good, unstable, or poor adherence. Co-variables of interest included age, sex, time since HIV diagnosis, ART duration, current ART regimen, HIV transmission route, comorbidity, HIV-1 RNA viral load (VL, and CD4 cell count. Patients self-reported the number of missed doses and provided their specific reasons for nonadherent behavior. Statistical analyses were performed using Fisher’s extended exact test, Kruskal–Wallis test, and logistic regression models.Results: Our study assessed 215 participants with good (n=162, unstable (n=36, and poor adherence (n=17. Compared to patients with good adherence, patients with unstable and poor adherence reported more often to have missed at least one dose during the last week (good 11% vs unstable 47% vs poor 63%, p<0.001. Physicians’ adherence assessment was concordant with patients’ self-reports of missed doses during the last week (no vs one or more in 81% cases. Similarly, we found a

  16. Gender differences in clinical, immunological, and virological outcomes in highly active antiretroviral-treated HIV–HCV coinfected patients

    Directory of Open Access Journals (Sweden)

    Joel Emery

    2010-05-01

    Full Text Available Joel Emery1, Neora Pick2, Edward J Mills3, Curtis L Cooper11The Ottawa Hospital Division of Infectious Diseases, University of Ottawa, Ottawa, Canada; 2Oak Tree Clinic, BC Women’s Hospital, Vancouver, Canada; 3Faculty of Health Sciences, University of Ottawa, Ottawa, CanadaObjective: The influence of biological sex on human immunodeficiency virus (HIV antiretroviral treatment outcome is not well described in HIV–hepatitis C (HCV coinfection.Methods: We assessed patients’ clinical outcomes of HIV–HCV coinfected patients initiating antiretroviral therapy attending the Ottawa Hospital Immunodeficiency Clinic from January 1996 to June 2008.Results: We assessed 144 males and 39 females. Although similar in most baseline characteristics, the CD4 count was higher in females (375 vs 290 cells/μL. Fewer females initiated ritonavir-boosted regimens. The median duration on therapy before interruption or change was longer in males (10 versus 4 months (odds ratio [OR] 1.40 95% confidence interval: 0.95–2.04; P = 0.09. HIV RNA suppression was frequent (74% and mean CD4 count achieved robust (over 400 cells/μL at 6 months, irrespective of sex. The primary reasons for therapy interruption in females and males included: gastrointestinal intolerance (25% vs 19%; P = 0.42; poor adherence (22% vs 15%; P = 0.31; neuropsychiatric symptoms (19% vs 5%; P = 0.003; and lost to follow-up (3% vs 13%; P = 0.08. Seven males (5% and no females discontinued therapy for liver-specific complications. Death rate was higher in females (23% vs 7%; P = 0.003.Conclusion: There are subtle differences in the characteristics of female and male HIV–HCV coinfected patients that influence HIV treatment decisions. The reasons for treatment interruption and change differ by biological sex. This knowledge should be considered when starting HIV therapy and in efforts to improve treatment outcomes.Keywords: AIDS, HIV, HCV, coinfection, HAART, viral load, women, gender differences

  17. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

    Science.gov (United States)

    Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

    2016-07-12

    New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and

  18. Sexual risk behaviors among HIV-patients receiving antiretroviral therapy in Southern Thailand: roles of antiretroviral adherence and serostatus disclosure.

    Science.gov (United States)

    Thanawuth, Nattasiri; Rojpibulstit, Malee

    2016-01-01

    The objective of this study was to examine the extent of unprotected sex among patients already established in HIV-medical care and their associated factors. Sexually active patients who were receiving antiretroviral therapy (ART) from five public hospitals in Trang province, Southern Thailand, were interviewed. Of 279 studied patients, 37.3% had unprotected sex in the prior 3 months and 27.2% did not disclose their serostatus to sexual partners. The median duration interquartile range (IQR) of using ART was 47 (27-60) months and 26.7% were non-adherent to ART (i.e., taking less than 95% of the prescribed doses). More than one-third had the perception that ART use would protect against HIV transmission even with unprotected sex. About 36.6% reported that they were unaware of their current CD4 counts and nearly one-third did not receive any safe sex counseling at each medical follow-up. After adjustment for potential confounders, non-adherence to ART and HIV-nondisclosure were strongly associated with an increase in the risk of unprotected sex with the adjusted odds ratio (aOR) of 5.03 (95% CI 2.68-9.44) and 3.89 (95% CI 1.57-9.61), respectively. In contrast, the risk for engaging in unprotected sex was less likely among patients having a negative-serostatus partner (aOR = 0.30; 95% CI 0.12-0.75), a longer duration of the use of ART (aOR = 0.98; 95%CI 0.97-0.99) and an unawareness of their current CD4 levels (aOR = 0.54; 95% CI 0.30-0.99). To maximize the benefits from ART, there should be a bigger emphasis on the "positive prevention" program and more efforts are needed to target the population at risk for unprotected sex. Strategies to encourage adherence to ART and for disclosure of serostatus are also required.

  19. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis

    NARCIS (Netherlands)

    Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Chau, Nguyen Van Vinh; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James

    2011-01-01

    The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown. We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to

  20. Frequency and Predictors for Late Start of Antiretroviral Therapy in Primary Care Clinics, Kampala, Uganda

    NARCIS (Netherlands)

    Sendagire, Ibrahim; Cobelens, Frank; Kambugu, Andrew; Konde-Lule, Joseph; Schim van der Loeff, Maarten

    2012-01-01

    Background: Access to antiretroviral treatment (ART) has improved greatly in many parts of the world, including Uganda, yet, many patients delay to start ART even when registered within the HIV services. We assessed, in a routine ambulatory care setting, what proportion of patients start ART late