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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 <350 cells/microL (for DC vs. VS, 31% vs. 8%) 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 <350 cells/microL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the...

  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

    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...... than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic.......9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4...

  3. 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

  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 ......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 observation. METHODS: A total of 5,472 patients with CD4+ T-cell counts >350 cells/mm3 were recruited and randomized to either continuous ART (the viral suppression arm; VS) or CD4+ T-cell count-guided use of ART (the drug conservation arm; DC). RESULTS: Major CVD events developed in 79 patients. The hazard...... ratio (HR) for risk of CVD events for DC versus VS was 1.57 (95% confidence interval 1.00-2.46; P=0.05). There was no evidence that being off ART or a higher current HIV viral load were associated with increased CVD risk. Total cholesterol and low-density lipoprotein cholesterol were reduced as a result...

  5. T Cell Subsets in HIV Infected Patients after Successful Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ostrowski, Sisse Rye; Katzenstein, Terese Lea;

    2012-01-01

    Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell...

  6. Langerhans cells in periodontal disease of HIV- and HIV+ patients undergoing highly active antiretroviral therapy

    OpenAIRE

    Takeshi Kato Segundo; Giovanna Ribeiro Souto; Ricardo Alves Mesquita; Fernando Oliveira Costa

    2011-01-01

    The aim of this study was to assess and compare quantitatively the presence of S100+ Langerhans cells (LC) by immunochemistry techniques in HIV+ and HIV- gingivitis and periodontitis subjects. Additionally, it aimed to evaluate the correlation among densities of these cells with CD4+ and CD8+ T cells, and viral load levels in HIV+ subjects, all using Highly Active Antiretroviral Therapy (HAART). The samples were allocated into four groups: 1) 15 subjects with moderate chronic periodontitis (M...

  7. CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

    OpenAIRE

    Killian, M. Scott; Roop, Jeremy; Ng, Sharon; Frederick M Hecht; Levy, Jay A.

    2009-01-01

    CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course. In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment. CD8+ lymphocytes from subjects with untreated primary HIV-1 in...

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

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    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

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

    International Nuclear Information System (INIS)

    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

  10. 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 was to ...... was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals....

  11. Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells.

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    Sekar Natesampillai

    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

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

    NARCIS (Netherlands)

    Mocroft, A.; Phillips, A.N.; Gatell, J.; Horban, A.; Ledergerber, B.; Zilmer, K.; Jevtovic, D.; Maltez, F.; Podlekareva, D.; Lundgren, J.D.; Burger, D.M.

    2013-01-01

    BACKGROUND: 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 stud

  14. Langerhans cells in periodontal disease of HIV- and HIV+ patients undergoing highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Takeshi Kato Segundo

    2011-06-01

    Full Text Available The aim of this study was to assess and compare quantitatively the presence of S100+ Langerhans cells (LC by immunochemistry techniques in HIV+ and HIV- gingivitis and periodontitis subjects. Additionally, it aimed to evaluate the correlation among densities of these cells with CD4+ and CD8+ T cells, and viral load levels in HIV+ subjects, all using Highly Active Antiretroviral Therapy (HAART. The samples were allocated into four groups: 1 15 subjects with moderate chronic periodontitis (MCP, HIV+; 2 15 subjects with MCP, HIV-; 3 10 subjects with gingivitis (G, HIV+; and 4 10 subjects with G, HIV-. The S100+ cells were assessed in the pocket epithelium, gingival epithelium, and lamina propria. A statistically significant increase of total S100+ cells in HIV+ periodontitis subjects was observed in relation to HIV- periodontitis subjects. No increase of S100+ cells with increased inflammation was observed. No statistically significant correlation among S100+ cells and blood levels of CD4, CD8, and viral load was observed. In conclusion, the use of HAART can aid in achieving viral loads, and it is suggested that it may prevent the destruction of the LC.

  15. Intestinal B cell hyperactivity in AIDS is controlled by highly active antiretroviral therapy

    OpenAIRE

    Nilssen, D E; Øktedalen, O; Brandtzaeg, P

    2004-01-01

    Background: It is well documented that highly active antiretroviral therapy (HAART) restores systemic immunity to human immunodeficiency virus (HIV) but the effect of this treatment on the mucosal immune system is less clear.

  16. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  17. Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

    Directory of Open Access Journals (Sweden)

    Kanmogne GD

    2012-05-01

    Full Text Available Georgette D Kanmogne1, Sangya Singh1, Upal Roy1, Xinming Liu1, JoEllyn McMillan1, Santhi Gorantla1, Shantanu Balkundi1, Nathan Smith1, Yazen Alnouti2, Nagsen Gautam2, You Zhou3, Larisa Poluektova1, Alexander Kabanov2, Tatiana Bronich2, Howard E Gendelman11Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, 2Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE; 3Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USAAbstract: Despite the successes of antiretroviral therapy (ART, HIV-associated neurocognitive disorders remain prevalent in infected people. This is due, in part, to incomplete ART penetration across the blood–brain barrier (BBB and lymph nodes and to the establishment of viral sanctuaries within the central nervous system. In efforts to improve ART delivery, our laboratories developed a macrophage-carriage system for nanoformulated crystalline ART (nanoART (atazanavir, ritonavir, indinavir, and efavirenz. We demonstrate that nanoART transfer from mononuclear phagocytes (MP to human brain microvascular endothelial cells (HBMEC can be realized through cell-to-cell contacts, which can facilitate drug passage across the BBB. Coculturing of donor MP containing nanoART with recipient HBMEC facilitates intercellular particle transfer. NanoART uptake was observed in up to 52% of HBMEC with limited cytotoxicity. Folate coating of nanoART increased MP to HBMEC particle transfer by up to 77%. To translate the cell assays into relevant animal models of disease, ritonavir and atazanavir nanoformulations were injected into HIV-1-infected NOD/scid-γcnull mice reconstituted with human peripheral blood lymphocytes. Atazanavir and ritonavir levels in brains of mice treated with folate-coated nanoART were three- to four-fold higher than in mice treated with noncoated particles. This was associated with decreased viral load in the spleen and

  18. Longitudinal microarray analysis of cell surface antigens on peripheral blood mononuclear cells from HIV+ individuals on highly active antiretroviral therapy

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    Wang Bin

    2008-03-01

    Full Text Available Abstract Background The efficacy of highly active antiretroviral therapy (HAART determined by simultaneous monitoring over 100 cell-surface antigens overtime has not been attempted. We used an antibody microarray to analyze changes in the expression of 135 different cell-surface antigens overtime on PBMC from HIV+ patients on HAART. Two groups were chosen, one (n = 6 achieved sustainable response by maintaining below detectable plasma viremia and the other (n = 6 responded intermittently. Blood samples were collected over an average of 3 years and 5–8 time points were selected for microarray assay and statistical analysis. Results Significant trends over time were observed for the expression of 7 cell surface antigens (CD2, CD3epsilon, CD5, CD95, CD36, CD27 and CD28 for combined patient groups. Between groups, expression levels of 10 cell surface antigens (CD11a, CD29, CD38, CD45RO, CD52, CD56, CD57, CD62E, CD64 and CD33 were found to be differential. Expression levels of CD9, CD11a, CD27, CD28 and CD52, CD44, CD49d, CD49e, CD11c strongly correlated with CD4+ and CD8+ T cell counts, respectively. Conclusion Our findings not only detected markers that may have potential prognostic/diagnostic values in evaluating HAART efficacy, but also showed how density of cell surface antigens could be efficiently exploited in an array-like manner in relation to HAART and HIV-infection. The antigens identified in this study should be further investigated by other methods such as flow cytometry for confirmation as biological analysis of these antigens may help further clarify their role during HAART and HIV infection.

  19. T Cell Subsets in HIV Infected Patients after Successful Combination Antiretroviral Therapy: Impact on Survival after 12 Years

    OpenAIRE

    Rönsholt, Frederikke Falkencrone; Ostrowski, Sisse Rye; Katzenstein, Terese Lea; Ullum, Henrik; Gerstoft, Jan

    2012-01-01

    Objectives Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell subsets after 18 months of cART and overall survival during 12 years of follow up. Methods A cohort of 101 HIV infected patients who had undetectable plasma HIV after starting cART was in...

  20. The antiretroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cells

    OpenAIRE

    De Rossi, Alessandra; Russo, Giuseppe; Puca, Andrew; La Montagna, Raffaele; Caputo, Mariella; Mattioli, Eliseo; Lopez, Massimo; Giordano, Antonio; Pentimalli, Francesca

    2009-01-01

    Abacavir is one of the most efficacious nucleoside analogues, with a well-characterized inhibitory activity on reverse transcriptase enzymes of retroviral origin, and has been clinically approved for the treatment of AIDS. Recently, Abacavir has been shown to inhibit also the human telomerase activity. Telomerase activity seems to be required in essentially all tumours for the immortalization of a subset of cells, including cancer stem cells. In fact, many cancer cells are dependent on telome...

  1. Case of relapsed AIDS-related plasmablastic lymphoma treated with autologous stem cell transplantation and highly active antiretroviral therapy

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    Hiroki Goto

    2011-03-01

    Full Text Available Plasmablastic lymphoma is a rare and aggressive malignancy strongly associated with HIV infection. The refractory/relapsed disease rate is high, and the survival rate is characteristically poor. There are no satisfactory salvage regimens for relapsed cases. We successfully performed autologous stem cell transplantation using a regimen consisting of MCNU (ranimustine, etoposide, cytarabine, and melphalan in a Japanese patient with relapsed AIDS-related plasmablastic lymphoma of the oral cavity. Highly active antiretroviral therapy continued during the therapy. Therapy-related toxicity was tolerable, and a total of 40 Gy of irradiation was administered after autologous stem cell transplantation. The patient has remained in complete remission for 16 months since transplantation.

  2. Factors associated with short-term changes in HIV viral load and CD4+ cell count in antiretroviral-naive individuals

    OpenAIRE

    2014-01-01

    Objectives: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4+ cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. Design: An observational cohort collaboration study. Methods: A total of 158 385 pairs of consecutive viral load and CD4+ cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual...

  3. Factors associated with short-term changes in HIV viral load and CD4 R cell count in antiretroviral-naive individuals

    OpenAIRE

    F. Nakagawa; Grp, NHPW; Ep, COHIV; EuroCoord

    2014-01-01

    Objectives: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4þ cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. Design: An observational cohort collaboration study. Methods: A total of 158 385 pairs of consecutive viral load and CD4þ cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database ...

  4. T cell subsets in HIV infected patients after successful combination antiretroviral therapy: impact on survival after 12 years.

    Directory of Open Access Journals (Sweden)

    Frederikke Falkencrone Rönsholt

    Full Text Available OBJECTIVES: Immune activation is decreased by combination antiretroviral therapy (cART in patients infected with human immunodeficiency virus (HIV, but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell subsets after 18 months of cART and overall survival during 12 years of follow up. METHODS: A cohort of 101 HIV infected patients who had undetectable plasma HIV after starting cART was included in 1997-1998. T cell subsets were analyzed by flowcytometry after 18 months of cART. Relation to survival was calculated using Kaplan-Meier curves and multiple Cox regression. RESULTS: Seventeen patients died during the observation period. The leading causes of death were non-AIDS cancer and cardiovascular disease. Higher levels of CD8 memory T cells (CD8+,CD45RO+,CD45RA- showed a significant beneficiary effect on survival, HR of 0.95 (95% confidence interval 0.91-0.99, P = 0.016 when adjusted for age, nadir CD4 count, CD4 count, and AIDS and hepatitis C status. T cell activation was not associated with increased risk of death. CONCLUSIONS: Larger and longitudinal studies are needed to accurately establish prognostic factors, but overall results seem to suggest that prognostic information exists within the CD8 compartment.

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

    International Nuclear Information System (INIS)

    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-1hi expressing T cells and Tregs in PBMCs, and PD-1hi Tregs in lymph nodes. It transiently decreased expression of Ki67 and α4β7 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-1hi 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-1hi cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1hi cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire

  6. 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.

  7. Rifaximin has a Marginal Impact on Microbial Translocation, T-cell Activation and Inflammation in HIV-Positive Immune Non-responders to Antiretroviral Therapy – ACTG A5286

    OpenAIRE

    Tenorio, Allan R.; Chan, Ellen S; Bosch, Ronald J.; Macatangay, Bernard J.C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam

    2014-01-01

    Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART).

  8. 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.

  9. Increased Rate of CD4+ T-Cell Decline and Faster Time to Antiretroviral Therapy in HIV-1 Subtype CRF01_AE Infected Seroconverters in Singapore

    OpenAIRE

    Oon Tek Ng; Li Lin; Oliver Laeyendecker; Quinn, Thomas C.; Yong Jiang Sun; Cheng Chuan Lee; Yee Sin Leo

    2011-01-01

    BACKGROUND: It remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART). METHODS: We recruited ART-naive patients with known dates of seroconversion between...

  10. Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection.

    Directory of Open Access Journals (Sweden)

    Nancie M Archin

    Full Text Available BACKGROUND: Human immunodeficiency virus (HIV infection that persists despite antiretroviral therapy (ART is a daunting problem. Given the limited evidence that resting CD4+ T cell infection (RCI is affected by the histone deacetylase (HDAC inhibitor valproic acid (VPA, we measured the stability of RCI and residual viremia in patients who added VPA with or without raltegravir (RAL, or enfuvirtide (ENF with or without VPA, to standard ART. METHODS: Patients with plasma HIV RNA50% was seen in six volunteers after the addition of RAL and VPA. In 4 of the 6 patients this lack of effect might be attributed to intermittent viremia, low VPA levels, or intermittent study therapy adherence. Overall, there was no effect of the addition of RAL or ENF on low-level viremia measured by SCA. CONCLUSIONS: The prospective addition of VPA and RAL, VPA and ENF, or ENF failed to progressively reduce the frequency of RCI, or ablate intermittent and low-level viremia. New approaches such as more potent HDAC inhibition, alone or in combination with intensified ART or other agents that may disrupt proviral latency must be pursued.

  11. 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 ...... lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P <.0001). The incidence of HL is not reduced by cART, and patients whose CD4 cell counts decline despite suppression of HIV-1 replication on cART may harbor HL.......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...

  12. 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 ...... lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P <.0001). The incidence of HL is not reduced by cART, and patients whose CD4 cell counts decline despite suppression of HIV-1 replication on cART may harbor HL.......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...

  13. HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) -Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

    DEFF Research Database (Denmark)

    Skov Jensen, Sanne; Fomsgaard, Anders; Borggren, Marie; Tingstedt, Jeanette Linnea; Gerstoft, Jan; Kronborg, Gitte; Rasmussen, Line Dahlerup; Pedersen, Court; Karlsson, Ingrid

    2015-01-01

    Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated...... the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion......, compared to the individuals initiating ART at a low CD4+ T cell count (<350 cells/μl blood) and the ART-naïve individuals. The frequency of CD16 expressing natural killer (NK) cells correlated with both the duration of ART and Granzyme B (GzB) activity. In contrast, the plasma titer of antibodies mediating...

  14. Antiretroviral therapy

    DEFF Research Database (Denmark)

    Nam, Nguyen Thi Thu; Bygbjerg, Ib Christian; Mogensen, Hanne Overgaard;

    2011-01-01

    -sectional study using structured questionnaires and CD4 cell count was conducted with 353 HIV-positive women recruited from groups of people living with HIV/AIDS (PLWHA), by snowball technique through member of PLWHA groups and the local AIDS management system (Provincial AIDS Center (PAC)). The percentage of HIV...

  15. 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...... remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has...

  16. 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

  17. 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....

  18. Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Sasisopin Kiertiburanakul

    2014-03-01

    Full Text Available Introduction: Although antiretroviral therapy (ART has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation. Methods: Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm3 or prior AIDS diagnosis. Predictors for late ART initiation and mortality were determined. Results: A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR CD4 cell count at ART initiation was 150 (46–241 cells/mm3. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm3 in 2008 to a peak of 302 cells/mm3 after 2011 (p for trend 0.002. The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001. Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001, sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001 and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001. Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010, sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002, age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001 and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035. Conclusions: Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients

  19. Lon protease and eiF2α are involved in acute, but not prolonged, antiretroviral induced stress response in HepG2 cells.

    Science.gov (United States)

    Nagiah, Savania; Phulukdaree, Alisa; Chuturgoon, Anil A

    2016-05-25

    Lon protease, an ATP dependent mitochondrial protease, is important in mitochondrial protein maintenance. Disruption of protein homeostasis and mitochondrial dysfunction is associated with lipodystrophy, metabolic syndrome and accelerated aging, and are commonly observed in patients on long term antiretroviral therapy. Sirtuin 3 (SIRT3) is a post-translational regulator of Lon and regulates antioxidant response. We previously showed the nucleoside analogues (NRTIs), Zidovudine (AZT; 7.1 μM), Stavudine (d4T; 4 μM), and Tenofovir (TFV; 1.2 μM) induced oxidative stress and mitochondrial dysfunction in human hepatoma (HepG2) cells at 24 h (h) and 120 h. We conducted a mitochondrial proteomic assessment of homeostasis in the same model, using the same NRTIs. Protein expression of Lon, SIRT3, heat shock protein (HSP) 60, phospho-eukaryotic translation initiation factor 2α (p-eIF2α; Ser51) and phospho-c-jun N-terminal kinase (p-JNK; Thr183/Tyr185) were quantified by western blots. The data showed all stress responses were significantly increased in HepG2 cells by all antiretroviral drugs at 24 h (p initiated by endoplasmic reticulum stress: p-eIF2α (p = 0.001) and p-JNK (p = 0.0029), were significantly reduced following prolonged treatment. SIRT3 was maintained at elevated levels in the treated cells following prolonged exposure (p < 0.001). We conclude that the ATP dependent proteins are more relevant to acute toxicity, while SIRT3 confers protection over prolonged periods of toxicity. PMID:27041070

  20. 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, B K;

    2005-01-01

    highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with < or = 200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4...... expression on CD3- CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected...... follow-up (both P < 0.001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0.05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B...

  1. Antiretroviral drug resistance testing

    Directory of Open Access Journals (Sweden)

    Sen Sourav

    2006-01-01

    Full Text Available While antiretroviral drugs, those approved for clinical use and others under evaluation, attempt in lowering viral load and boost the host immune system, antiretroviral drug resistance acts as a major impediment in the management of human immune deficiency virus type-1 (HIV-1 infection. Antiretroviral drug resistance testing has become an important tool in the therapeutic management protocol of HIV-1 infection. The reliability and clinical utilities of genotypic and phenotypic assays have been demonstrated. Understanding of complexities of interpretation of genotyping assay, along with updating of lists of mutation and algorithms, and determination of clinically relevant cut-offs for phenotypic assays are of paramount importance. The assay results are to be interpreted and applied by experienced HIV practitioners, after taking into consideration the clinical profile of the patient. This review sums up the methods of assay currently available for measuring resistance to antiretroviral drugs and outlines the clinical utility and limitations of these assays.

  2. Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

    DEFF Research Database (Denmark)

    Jensen, Sanne Skov; Fomsgaard, Anders; Larsen, Tine Kochendorf; Tingstedt, Jeanette Linnea; Gerstoft, Jan; Kronborg, Gitte; Pedersen, Court; Karlsson, Ingrid

    2015-01-01

    cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated......CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether...... restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T...

  3. Factors associated with short-term changes in HIV viral load and CD4+ cell count in antiretroviral-naive individuals

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2014-01-01

    OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. DESIGN: An observational cohort...... collaboration study. METHODS: A total of 158 385 pairs of consecutive viral load and CD4(+) cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual changes and factors associated with these changes were estimated using generalized estimating equations...... (95% CI) CD4(+) cell count change was -78.0 (-80.1 to -76.0) cell/μl per year and it was strongly associated with a higher current viral load: for every 1 log10 copies/ml higher, CD4(+) cell count declined by an additional 37.6 cells/μl per year (P < 0.001). Current viral load was a stronger predictor...

  4. 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

    OpenAIRE

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

    2013-01-01

    Background 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 therefo...

  5. Progress in antiretroviral drug delivery using nanotechnology

    Directory of Open Access Journals (Sweden)

    Rama Mallipeddi

    2010-07-01

    Full Text Available Rama Mallipeddi, Lisa Cencia RohanUniversity of Pittsburgh, Department of Pharmaceutical Sciences, School of Pharmacy, Magee Womens Research Institute, Pittsburgh, PA, USAAbstract: There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV. More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid, liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease.Keywords: drug delivery, HIV, antiretrovirals, nanoparticles, liposomes, dendrimers

  6. CD4(+) T Cell Response to Lamivudine, Stavudine and Nevirapine in Human Immunodeficiency Virus Infected Antiretroviral-Naive Men in Nigeria.

    Science.gov (United States)

    Sule, Waidi Folorunso; Sani, Enejoh Simon

    2011-12-01

    Increase of (≥) 50 CD4(+) T cells/μl in post-commencement of highly active antiretroviral therapy (HAART) is acceptable as indicator of therapeutic success (TS). We therefore hypothesized that median change in CD4 count of the TS and therapeutic failure (TF) groups were comparable after 3 months; and that no associations existed between HAART outcome and adherence to therapy. One hundred Human immunodeficiency virus (HIV) infected antiretroviral (ARV) naive men on lamivudine + stavudine + nevirapine at Federal Medical Centre (FMC), Lokoja, Kogi State, Nigeria were studied. Data of the men were obtained with interviewer-administered questionnaire forms. Their ethylene diamine tetra acetic acid (EDTA)-treated whole blood samples were analysed with Partec CyFlow(®) Counter for pre-HAART and follow-up CD4 counts. Adherence to the ARV regimen was recorded for each patient as self-reported. We used Mann-Whitney U test, Kruskal-Wallis, Wilcoxon's matched pair and CHI(2) statistical tests for analyses. Overall adherence rate was 95.0%. Though the median follow-up CD4 count was higher (P = 0.001) than the pre-HAART value; only 85% of the men attained TS (increase of ≥50 cells/μl) at follow-up. Median change in CD4 count (+104.0 cells/μl; n = 85) of the TS was higher (P = 0.001) than that (-8.0 cells/μl; n = 15) of TF group; the two groups were however, comparable in age (P = 0.17) and body weight (P = 0.96). Only adherence and pre-HAART CD4 counts were associated (P = 0.001) with HAART outcome; while only age apparently influenced (P = 0.01) adherence rate. Eighty-five percent of the men benefited from the HAART. The success was apparently due to adherence and less than or (≤) 200 pre-HAART CD4 counts; while age ≥40 years appearently reduced adherence level. PMID:23637509

  7. Longitudinal changes of peripheral blood DC subsets and regulatory T cells in Chinese chronic HIV-1-infected patients during antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Mei Zhang

    Full Text Available It has been emphasized that chronic generalized immune dysfunction is the leading event in the pathogenesis of HIV infection, in which the contribution of dendritic cells (DCs and regulatory T cells (Tregs should not be underestimated. In current study, we assessed the longitudinal changes of peripheral blood DC subsets and Tregs in chronically asymptomatic treatment-naive HIV-1-infected patients during 60 weeks of antiretroviral therapy (ART, and compared with those in healthy controls and long term non-progressors (LTNPs. Blood samples were collected at week 0, 4, 12, 24, 48 and 60 of treatment to measure the counts of DC subsets and Tregs by flow cytometry and IFN-a plasma levels by ELISA. The counts of myeloid dendritic cells (mDCs increased during ART, reaching similar levels to healthy controls at week 60 post ART but still lower than those of LTNPs. In HIV-1-infected patients, the mDCs counts were directly correlated with CD4 counts during ART. Changes in mDCs at week 8 were positively correlated with the changes in CD4 counts at week 60 post ART. However, the counts and function of plasmacytoid dendritic cells (pDCs remained relatively stable during ART, and similar to those in healthy controls and LTNPs. The percentage of Tregs increased before ART and normalized after ART. Importantly, we found pDCs counts were associated with percentage of Tregs during ART, which may help in understanding of the role of these cells in HIV infection.

  8. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load

    DEFF Research Database (Denmark)

    Obel, Niels

    2012-01-01

    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....

  9. Increased rate of CD4+ T-cell decline and faster time to antiretroviral therapy in HIV-1 subtype CRF01_AE infected seroconverters in Singapore.

    Directory of Open Access Journals (Sweden)

    Oon Tek Ng

    Full Text Available BACKGROUND: It remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS to antiretroviral therapy (ART. METHODS: We recruited ART-naive patients with known dates of seroconversion between October 2002 and December 2007 at the Singapore Communicable Disease Centre, the national reference treatment centre. Multilevel mixed-effects models were used to analyse the rate of CD4+ T-cell decline. Time from EDS to ART was analyzed with the Kaplan-Meier survival method and compared with Cox proportional hazards models. RESULTS: 54 patients with previously assigned HIV-1 subtypes (24 CRF01_AE, 17 B, 8 B', 1 CRF33_01B, 3 CRF34_01B and 1 G were observed for 89 patient-years. Subtype CRF01_AE and non-CRF01_AE infected patients did not differ in age, gender, risk factor, rate of symptomatic seroconversion, baseline CD4+ T-cell count, log(10 viral load or haemoglobin concentration. The estimated annual rate of CD4+ T-cell loss was 58 cells/mm(3/year (95% CI: 7 to 109; P = 0.027 greater in subtype CRF01_AE infected patients compared to non-CRF01_AE patients, after adjusting for age, baseline CD4+ T-cell count and baseline log(10 viral load. The median time from EDS to ART was 1.8 years faster comparing CRF01_AE to non-CRF01_AE infected patient with a 2.5 times (95% CI: 1.2-5.0; P = 0.013 higher hazard for ART initiation, after controlling for age, baseline CD4+ T-cell count and baseline log(10 viral load. CONCLUSIONS: Infecting subtype significantly impacted the rate of CD4+ T-cell loss and time to treatment in this cohort. Studies to understand the biological basis for this difference could further our understanding of HIV pathogenesis.

  10. 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

    BACKGROUND: Natural killer (NK) cell phenotype and function have recently gained much attention as playing crucial roles in antibody-dependent cellular cytotoxicity (ADCC). We investigated NK cell function, as measured by ADCC, in HIV-1-positive individuals before and 6 months after highly active...

  11. 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...... with detection of TDR, with virological (viral load<500 copies/mL) and CD4 count response (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological...... suppression (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral...

  12. 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...

  13. 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

    ,000 copies/ml. By contrast, among patients taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, the CD4(+) T-cell count significantly decreased when the viral load was 500-9,999 copies/ml (-18.6 cells/mm(3), 95% CI -33.8--3.5) and decreased at a faster rate when the viral load was...

  14. Persistent HIV-1 replication during antiretroviral therapy

    OpenAIRE

    Martinez-Picado, Javier; Deeks, Steven G

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on ef...

  15. Confocal fluorescence microscopy: An ultra-sensitive tool used to evaluate intracellular antiretroviral nano-drug delivery in HeLa cells

    Science.gov (United States)

    Mandal, Subhra; Zhou, You; Shibata, Annemarie; Destache, Christopher J.

    2015-08-01

    In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world's major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARV has serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as drug delivery system. However, important aspects of cARV-NPs that require special emphasis are their cellular-uptake, potency, and sustained drug release efficiency over-time. In this article, ultra-sensitive confocal microscopy is been used to evaluate the uptake and sustained drug release kinetics of cARV-NPs in HeLa cells. To evaluate with the above goal, instead of cARV-drug, Rhodamine6G dye (fluorescent dye) loaded NPs (Rho6G NPs) have been formulated. To correlate the Rhodamin6G release kinetics with the ARV release from NPs, a parallel HPLC study was also performed. The results obtained indicate that Rho6G NPs were efficiently taken up at low concentration (delivery with the potential to reduce drug dosage as well as the number of drug administrations per month.

  16. Status of immunity against PVB19 in HIV-infected patients according to CD4 + cell count, and antiretroviral therapy regimen groups

    Directory of Open Access Journals (Sweden)

    Alireza Abdollahi

    2014-01-01

    Full Text Available Background: Human Parvovirus B19 (PVB19 is among the aetiology of aplastic crisis in human immunodeficiency virus (HIV-infected patients. Several studies have indicated the importance of an infection agent in bringing about complications in immuno-compromised patients. The current study aims to determine the seroprevalence of IgM and IgG antibodies to PVB19 among HIV-positive patients and its association with clinical and epidemiological factors. Materials and Methods: In a case control study, 90 HIV-positive patients were compared with 90 sex and age matched healthy controls in terms of anti-PVB19 IgG and IgM along with other primary clinical and laboratory features. Results: The overall prevalence of positive anti-PVB19 IgG among HIV patients and controls were 81.1% and 28.9%, respectively (P < 0.001. None of the subjects showed positive results for anti-PVB19 IgM. Patients with CD4 + cell count <200 showed higher seroprevalence of positive anti-PVB19 IgG which did not reach statistically significant. However, anti-PVB19 IgG seropositivity differed significantly between HIV patients on different regimens of antiretroviral therapy (ART (P < 0.05. Conclusion: Immunity against PVB19 is more prevalent among HIV-positive patients compared to healthy controls. However, positive HIV status is not associated with acute PVB19 infection. The presence of anti-PVB19 IgG does not necessarily protect the body from further complications like anaemia. Given the results of the study, AIDS patients are recommended to undergo screening for parvovirus antibody in order to prevent complications like aplastic anaemia.

  17. 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

  18. 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. PMID:19702067

  19. 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....

  20. Chemical Library Screens Targeting an HIV-1 Accessory Factor/Host Cell Kinase Complex Identify Novel Anti-retroviral Compounds

    OpenAIRE

    Emert-Sedlak, Lori; Kodama, Toshiaki; Lerner, Edwina C.; Dai, Weixiang; Foster, Caleb; Day, Billy W.; Lazo, John S.; Smithgall, Thomas E

    2009-01-01

    Nef is an HIV-1 accessory protein essential for AIDS progression and an attractive target for drug discovery. Lack of a catalytic function makes Nef difficult to assay in chemical library screens. We developed a high-throughput screening assay for inhibitors of Nef function by coupling it to one of its host cell binding partners, the Src-family kinase Hck. Hck activation is dependent upon Nef in this assay, providing a direct readout of Nef activity in vitro. Using this screen, a unique diphe...

  1. Pharmacogenomics of antiretrovirals.

    Science.gov (United States)

    Roca, Bernardino

    2008-06-01

    HIV infection is a serious but treatable disease, yet current treatment is limited by development of resistance and high rates of adverse drug reactions. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be reliably measured. Increasing knowledge about genes implicated in pharmacokinetics, mode of action, efficacy, and toxicity of drugs has already provided relevant results for clinical practice, for example: The strong association of the abacavir hypersensitivity reaction with HLA-B*5701 permits testing patients for the allele, and if present avoiding the drug and therefore preventing the reaction. Persons with the allele CYP2B6*6 present higher efavirenz "area under the curve" and have increased risk of neuropsychological toxicity. Additional gene variants are being discovered that influence the action of antiretroviral drugs. And, moreover, it is expected that larger-scale comprehensive genome approaches will profoundly improve the landscape of knowledge of HIV therapy in the future. The present article shows some recent patents related to the treatment of viral infections. PMID:18673126

  2. Immune restoration disease and changes in CD4+ T-cell count in HIV- infected patients during highly active antiretroviral therapy at Zewditu memorial hospital, Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Kassu Afework

    2010-12-01

    Full Text Available Abstract Background Highly active antiretroviral therapy (HAART improves the immune function and decreases morbidity, mortality and opportunistic infections (OIs in HIV-infected patients. However, since the use of HAART, immune restoration disease (IRD has been described in association with many OIs. Our objective was to determine the proportion of IRD, changes in CD4+ T-cell count and possible risk factors of IRD in HIV-infected patients. Methods A retrospective study of all HIV- infected patients starting HAART between September 1, 2005 and August 31, 2006 at Zewditu memorial hospital HIV clinic, Addis Ababa, Ethiopia was conducted. All laboratory and clinical data were extracted from computerized clinic records and patient charts. Results A total of 1166 HIV- infected patients with mean ± SD age of 36 ± 9.3 years were on HAART. IRD was identified in 170 (14.6% patients. OIs diagnosed in the IRD patients were tuberculosis (66.5%, 113/170, toxoplasmosis (12.9%, 22/170, herpes zoster rash (12.9%, 22/170, Pneumocystis jirovecii pneumonia (4.1%, 7/170, and cryptococcosis (3.5%, 6/170. Of the 170 patients with IRD, 124 (72.9% patients developed IRD within the first 3 months of HAART initiation. Low baseline CD4+ T-cell count (odds ratio [OR], 3.16, 95% confidence interval [CI], 2.19-4.58 and baseline extra pulmonary tuberculosis (OR, 7.7, 95% CI, 3.36-17.65 were associated with development of IRD. Twenty nine (17.1% of the IRD patients needed to use systemic anti-inflammatory treatment where as 19(11.2% patients required hospitalization associated to the IRD occurrence. There was a total of 8 (4.7% deaths attributable to IRD. Conclusions The proportion and risk factors of IRD and the pattern of OIs mirrored reports from other countries. Close monitoring of patients during the first three months of HAART initiation is important to minimize clinical deterioration related to IRD.

  3. The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models.

    Science.gov (United States)

    Ford, Deborah; Robins, James M; Petersen, Maya L; Gibb, Diana M; Gilks, Charles F; Mugyenyi, Peter; Grosskurth, Heiner; Hakim, James; Katabira, Elly; Babiker, Abdel G; Walker, A Sarah

    2015-10-01

    In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003-2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm(3) or non-Candida World Health Organization stage 4 event (with CD4 count findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks. PMID:26316598

  4. 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......-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or...... another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. RESULTS: A total of 4685 patients were followed for a mean of 3.0 years. At study...

  5. Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV-specific CD4⁺ T-cell-dependent natural killer cell effector responses in chronically infected rhesus macaques.

    Science.gov (United States)

    Vargas-Inchaustegui, Diego A; Xiao, Peng; Demberg, Thorsten; Pal, Ranajit; Robert-Guroff, Marjorie

    2015-06-01

    Natural killer (NK) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti-viral immune responses. We have previously shown that interleukin-2-dependent NK and CD4(+) T-cell co-operative immune responses exist in long-term simian immunodeficiency virus (SIV) -infected controlling macaques and can be rescued in SIV-infected non-controlling macaques by a short course of antiretroviral therapy (ART). Given that co-operative responses may play an important role in disease prevention and therapeutic treatment, in the present study we sought to determine if these responses can be enhanced in chronically SIV-infected macaques by vaccination with a single-dose of envelope protein given during ART. To this end, we treated 14 chronically SIV-infected macaques with ART for 11 weeks and gave 10 of these macaques a single intramuscular dose of SIV gp120 at week 9 of treatment. ART significantly decreased plasma and mucosal viral loads, increased the numbers of circulating CD4(+) T cells in all macaques, and increased T-cell-dependent envelope- and gag-specific interferon-γ and tumour necrosis factor-α production by circulatory CD56(+) NK cells. The therapeutic envelope immunization resulted in higher envelope-specific responses compared with those in macaques that received ART only. Functional T-cell responses restored by ART and therapeutic Env immunization were correlated with transiently reduced plasma viraemia levels following ART release. Collectively our results indicate that SIV-specific T-cell-dependent NK cell responses can be efficiently rescued by ART in chronically SIV-infected macaques and that therapeutic immunization may be beneficial in previously vaccinated individuals. PMID:25626488

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

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C; Vella, S; Zilmer, K; Kjær, Jesper; Knysz, B; Phillips, AN; Mocroft, A; Lundgren, Jens Dilling

    2006-01-01

    BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western...

  7. In-Depth Analysis of Patient-Clinician Cell Phone Communication during the WelTel Kenya1 Antiretroviral Adherence Trial

    OpenAIRE

    van der Kop, Mia L; Karanja, Sarah; Thabane, Lehana; Marra, Carlo; Chung, Michael H.; Gelmon, Lawrence; Kimani, Joshua; Lester, Richard T.

    2012-01-01

    Background 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. Objectives 1) Describe problems participants identified through mobile phone support and reasons why participants did not respond to the messages; 2) ...

  8. No change in viral set point or CD4 cell decline among antiretroviral treatment-naïve, HIV-1-infected individuals enrolled in the Danish HIV Cohort Study in 1995-2010

    DEFF Research Database (Denmark)

    Helleberg, M; Kronborg, Gitte; Larsen, C S; Pedersen, Gitte; Pedersen, C; Obel, Niels; Gerstoft, Jan

    2013-01-01

    OBJECTIVES: Recent studies have reported faster progression of HIV infection than anticipated based on results from earlier studies. The aim of the present study was to examine if the virulence of HIV-1 infection changed in the period 1995-2010 among chronically HIV-infected individuals in Denmark....... METHODS: We included all patients registered in the Danish HIV Cohort Study, who were diagnosed in 1995-2009, had a CD4 count > 100 cells/μL at diagnosis and had at least two CD4 measurements prior to initiation of antiretroviral therapy (ART). Changes in viral set point and rate of CD4 cell decline from...... enrolment until the initiation of ART by calendar year of HIV diagnosis were analysed. Time to first CD4 count...

  9. Antiretroviral therapy: Shifting sands.

    Science.gov (United States)

    Sashindran, V K; Chauhan, Rajeev

    2016-01-01

    HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV. PMID:26900224

  10. Cytomegalovirus retinitis after initiation of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Zahra Ahmadinejad

    2013-10-01

    Full Text Available Patients with human immunodeficiency virus (HIV infection receiving antiretroviral therapy (ART, despite a reduced viral load and improved immune responses, may experience clinical deterioration. This so called "immune reconstitution inflammatory syndrome (IRIS" is caused by inflammatory response to both intact subclinical pathogens and residual antigens. Cytomegalovirus retinitis is common in HIV-infected patients on ART with a cluster differentiation 4 (CD4+ counts less than 50 cells/mm3. We reported a patient with blurred vision while receiving ART. She had an unmasking classic CMV retinitis after ART.

  11. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

    Directory of Open Access Journals (Sweden)

    Maia Hightower

    2003-02-01

    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.

  12. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral-naive indiv......OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral...... using survival methods. Ten age strata were chosen: less than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40-49, 50-54, 55-59 and 60 years or older; those aged 6 years or more were included in multivariable analyses. RESULTS: The four youngest age groups had 223, 184, 219 and 201 individuals...... and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological...

  13. 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.

  14. Nature of DNA lesions induced in human hepatoma cells, human colonic cells and human embryonic lung fibroblasts by the antiretroviral drug 3'-azido-3'-deoxythymidine

    International Nuclear Information System (INIS)

    This study tried to clarify the question if nuclear genotoxicity played a role in 3'-azido-3'-deoxythymidine (AZT) toxicity. We investigated cytotoxic and DNA-damaging effects of AZT on human hepatoma HepG2 and human colonic CaCo-2 cells as well as on human diploid lung fibroblasts HEL. The amount of induced DNA damage was measured by standard alkaline single cell gel electrophoresis (SCGE). The nature of induced DNA lesions was evaluated (1) by modified SCGE, which includes treatment of lysed cells with DNA repair enzymes Endo III and Fpg and enables to recognize oxidized bases of DNA, and (2) by SCGE processed in parallel at pH 13.0 (standard technique) and pH 12.1, which enables to recognize alkali labile DNA lesions and direct DNA strand breaks. Cytotoxicity of AZT was evaluated by the trypan blue exclusion technique. Our findings showed that 3-h treatment of cells with AZT decreased the viability of all cell lines studied. SCGE performed in the presence of DNA repair enzymes proved that AZT induced oxidative lesions to DNA in all cell types. In hepatoma HepG2 cells and embryonic lung fibroblasts HEL the majority of AZT-induced DNA strand breaks were pH-independent, i.e. they were identified at both pH values (12.1 and 13.0). These DNA lesions represented direct DNA breaks. In colonic Caco-2 cells DNA lesions were converted to DNA strand breaks particularly under strong alkaline conditions (pH > 13.0), which is characteristic for alkali-labile sites of DNA. DNA strand break rejoining was investigated by the standard comet assay technique during 48 h of post-AZT-treatment in HepG2 and Caco-2 cells. The kinetics of DNA rejoining, considered an indicator of DNA repair, revealed that AZT-induced DNA breaks were repaired in both cell types slowly, though HepG2 cells seemed to be more repair proficient with respect to AZT-induced DNA lesions

  15. Primary parotid B-cell lymphoma successfully treated with chemotherapy plus highly active antiretroviral therapy with prolonged survival and immune reconstitution in an acquired immunodeficiency syndrome patient: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2014-01-01

    Full Text Available Non-Hodgkin′s lymphoma (NHL is the second most common acquired immunodeficiency syndrome (AIDS-defining cancer. In this population, up to 70-80% of cases may present as extranodal location as the primary clinical manifestation of the neoplasm disease. Gastrointestinal tract is the most frequent location of AIDS-associated NHL. However, salivary gland involvement, including the parotid gland is a rare complication in human immunodeficiency virus (HIV-patients. Here, we describe a patient seropositive for the HIV, who developed a primary NHL of the parotid gland histologically classified as a high-grade diffuse large B-cell lymphoma. Patient was treated with a combination of chemotherapy plus highly active antiretroviral therapy with a good clinical, virological and immunological response and a prolonged survival, more than 5 years, without evidence of neoplasm relapse.

  16. 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

    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...... adipose tissue, and high muscle mass. PD-1 expression was not associated with age-related parameters. CONCLUSIONS: HIV-infection strongly affected CD8 (+) T cell differentiation and maturation, whereas age-related processes were only weakly associated with immune parameters. Our findings suggest that, in......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 of...

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

    Directory of Open Access Journals (Sweden)

    Graeme Meintjes

    2015-04-01

    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.

  18. Recovery of CD4+ T Cells in HIV patients with a stable virologic response to antiretroviral therapy is associated with polymorphisms of interleukin-6 and central major histocompatibility complex genes.

    Science.gov (United States)

    Fernandez, Sonia; Rosenow, Ann A; James, Ian R; Roberts, Steven G; Nolan, Richard C; French, Martyn A; Price, Patricia

    2006-01-01

    We investigated whether polymorphisms in genes associated with HIV disease progression and/or immune activation affect CD4+ T-cell recovery in HIV patients who began combination antiretroviral therapy (ART) with advanced immunodeficiency and achieved stable control of plasma viremia. Patients with CD4 T-cell counts 400 cells/microL (n = 37) on ART were compared. A multiple case-control logistic regression associated carriage of BAT1(1,2) or interleukin (IL)6-174(2,2) with low CD4 T-cell counts (P = 0.012). BAT1*2 uniquely marks the central major histocompatibility complex region of a conserved haplotype (HLA-A1,B8,BAT1*2,TNFA-308*2,DR3,DQ2). There was no association between alleles carried at CCR5Delta32, CCR5 59029, CCR5 59353, CCR2+190 (V64I), SDF1 3'UTR, IL1A+4845, IL1B+3953, IL4-589, IL10-592, IL10-R1+536, IL10-R1+1112, IL12B 3'UTR, TNFA-308, or TNFA-1031 and CD4 T-cell counts. We suggest that immune activation and/or CD4 T-cell apoptosis in HIV patients on effective ART is influenced by genetic factors. PMID:16340466

  19. Rifaximin has a Marginal Impact on Microbial Translocation, T-cell Activation and Inflammation in HIV-Positive Immune Non-responders to Antiretroviral Therapy – ACTG A5286

    Science.gov (United States)

    Tenorio, Allan R.; Chan, Ellen S.; Bosch, Ronald J.; Macatangay, Bernard J. C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam; Presti, Rachel; Deeks, Steven; Ebiasah, Ruth; Myers, Laurie; Borowski, LuAnn; Plants, Jill; Palm, David A.; Weibel, Derek; Putnam, Beverly; Lindsey, Elizabeth; Player, Amy; Albrecht, Mary; Kershaw, Andrea; Sax, Paul; Keenan, Cheryl; Walton, Patricia; Baum, Jane; Stroberg, Todd; Hughes, Valery; Coster, Laura; Kumar, Princy N.; Yin, Michael T.; Noel-Connor, Jolene; Tebas, Pablo; Thomas, Aleshia; Davis, Charles E.; Redfield, Robert R.; Sbrolla, Amy; Flynn, Teri; Davis, Traci; Whitely, Kim; Singh, Baljinder; Swaminathan, Shobha; McGregor, Donna; Palella, Frank; Aberg, Judith; Cavanagh, Karen; Santana Bagur, Jorge L.; Flores, Olga Méndez; Fritsche, Janice; Sha, Beverly; Slamowitz, Debbie; Valle, Sandra; Tashima, Karen; Patterson, Helen; Harber, Heather; Para, Michael; Eaton, Molly; Maddox, Dale; Currier, Judith; Cajahuaringa, Vanessa; Luetkemeyer, Annie; Dwyer, Jay; Fichtenbaum, Carl J.; Saemann, Michelle; Ray, Graham; Campbell, Thomas; Fischl, Margaret A.; Bolivar, Hector; Oakes, Jonathan; Chicurel-Bayard, Miriam; Tripoli, Christine; Weinman, D. Renee; Adams, Mary; Hurley, Christine; Dunaway, Shelia; Storey, Sheryl; Klebert, Michael; Royal, Michael

    2015-01-01

    Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). Methods. HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4+ T-cell counts <350 cells/mm3 were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Results. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8+T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. Conclusions. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8+T-cell activation. Trial registration number. NCT01466595. PMID:25214516

  20. Drug-Based Lead Discovery: The Novel Ablative Antiretroviral Profile of Deferiprone in HIV-1-Infected Cells and in HIV-Infected Treatment-Naive Subjects of a Double-Blind, Placebo-Controlled, Randomized Exploratory Trial

    Science.gov (United States)

    Saxena, Deepti; Spino, Michael; Tricta, Fernando; Connelly, John; Cracchiolo, Bernadette M.; Hanauske, Axel-Rainer; D’Alliessi Gandolfi, Darlene; Mathews, Michael B.; Karn, Jonathan; Holland, Bart; Park, Myung Hee; Pe’ery, Tsafi; Palumbo, Paul E.; Hanauske-Abel, Hartmut M.

    2016-01-01

    Antiretrovirals suppress HIV-1 production yet spare the sites of HIV-1 production, the HIV-1 DNA-harboring cells that evade immune detection and enable viral resistance on-drug and viral rebound off-drug. Therapeutic ablation of pathogenic cells markedly improves the outcome of many diseases. We extend this strategy to HIV-1 infection. Using drug-based lead discovery, we report the concentration threshold-dependent antiretroviral action of the medicinal chelator deferiprone and validate preclinical findings by a proof-of-concept double-blind trial. In isolate-infected primary cultures, supra-threshold concentrations during deferiprone monotherapy caused decline of HIV-1 RNA and HIV-1 DNA; did not allow viral breakthrough for up to 35 days on-drug, indicating resiliency against viral resistance; and prevented, for at least 87 days off-drug, viral rebound. Displaying a steep dose-effect curve, deferiprone produced infection-independent deficiency of hydroxylated hypusyl-eIF5A. However, unhydroxylated deoxyhypusyl-eIF5A accumulated particularly in HIV-infected cells; they preferentially underwent apoptotic DNA fragmentation. Since the threshold, ascertained at about 150 μM, is achievable in deferiprone-treated patients, we proceeded from cell culture directly to an exploratory trial. HIV-1 RNA was measured after 7 days on-drug and after 28 and 56 days off-drug. Subjects who attained supra-threshold concentrations in serum and completed the protocol of 17 oral doses, experienced a zidovudine-like decline of HIV-1 RNA on-drug that was maintained off-drug without statistically significant rebound for 8 weeks, over 670 times the drug’s half-life and thus clearance from circulation. The uniform deferiprone threshold is in agreement with mapping of, and crystallographic 3D-data on, the active site of deoxyhypusyl hydroxylase (DOHH), the eIF5A-hydroxylating enzyme. We propose that deficiency of hypusine-containing eIF5A impedes the translation of mRNAs encoding proline

  1. Correlation between cytokine serum levels, number of CD4+ T cells/mm³ and viral load in HIV-1 infected individuals with or without antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    D. A. Meira

    2004-01-01

    Full Text Available Seventy-nine HIV-1 infected patients were studied in three groups: Group G1 - 11 patients with no antiretroviral therapy; G2 - 40 patients undergoing antiretroviral therapy, 33 with only two nucleoside reverse transcriptase inhibitors (NRTI, and seven with two NRTI and one protease inhibitor (PI, all with viral load (VL equal or higher than 80 copies of plasma RNA/ml; Group G3 - 28 patients, 23 on highly active antiretroviral therapy (HAART, 18 with two NRTI and one PI, and five with two NRTI and one non-nucleoside reverse transcriptase inhibitor (NNRTI, the remaining five with combination of two NRTI. All G3 patients had undetectable viral load for at least the past six months. The control group (Gc included 20 normal blood donors without clinical complaints or signs of disease and negative for anti-HIV-1/2 antibodies. Serum cytokine levels pg/ml (TNF-alpha, INF-gamma, IL-2, IL-4, and IL-10 were determined in all patients including controls. CD4+ T and CD8+ T lymphocyte counts were made in the 79 patients by flow cytometry; VL determination was by NASBA technology. Analysis of results showed that the number of CD4+ T and CD8+ T lymphocytes were higher in G2 than G1, while VL was 0.5 log lower. G3 patients had similar lymphocyte values to G2, however they were chosen for G3 because their VL was undetectable, different by 4.0 log to G2. These results show the effect of antiretroviral treatment in G2 and G3 patients with better performance in the latter. Statistical difference was seen between the three groups and controls for serum cytokine behavior: TNF-alpha [H=48.323; pGc]; INF-gamma[H=28.992; pGc]; IL-4[H=48.323; pGc]; IL-10[H=47.256; pGc. There was no statistical difference in IL-2 values between all groups (H=6.071; p>0.10; G1=G2=G3=Gc. In absolute values however, G3 showed slightly lower TNF-alpha, IL-4, and IL-10, and higher INF-gamma and IL-2, to G1 and G2. This suggests a better performance in G3 patients, especially in IL-2 behavior

  2. 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 BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

  3. Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs)

    DEFF Research Database (Denmark)

    Kolte, L; Gaardbo, J C; Skogstrand, K;

    2008-01-01

    Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores...... if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38......(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly...

  4. Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs

    DEFF Research Database (Denmark)

    Kolte, L.; Gaardbo, J.C.; Skogstrand, K.;

    2009-01-01

    This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive...... T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human...... leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in...

  5. Adult antiretroviral therapy guidelines 2014

    Directory of Open Access Journals (Sweden)

    G. Meintjes

    2014-01-01

    Full Text Available These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in 2012. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART in southern Africa has continued. Cohort studies from the region show excellent clinical outcomes; however, ART is still being initiated late (in advanced disease in some patients, resulting in relatively high early mortality rates. New data on antiretroviral drugs have become available. Although currently few, there are patients in the region who are failing protease-inhibitor-based second-line regimens. To address this, guidelines on third-line therapy have been expanded.Please find a link to the update of this guideline: http://sajhivmed.org.za/index.php/hivmed/article/view/428

  6. Improving adherence to antiretroviral therapy

    OpenAIRE

    Nischal K; Khopkar Uday; Saple D

    2005-01-01

    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 dise...

  7. Antiretroviral Restriction Factors in Mice

    OpenAIRE

    Nair, Smita; Rein, Alan

    2014-01-01

    One of the most exciting areas in contemporary retrovirus research is the discovery of “restriction factors”. These are cellular proteins that act after virus entry to inhibit infection by or replication of retroviruses (and other viruses and intracellular pathogens). We briefly discuss here three antiretroviral restriction factors in mice: Fv1, APOBEC3, and tetherin, touching on both biological and molecular aspects of these restriction systems.

  8. Pharmacotoxicology of monocyte-macrophage nanoformulated antiretroviral drug uptake and carriage

    OpenAIRE

    Bressani, Rafael F.; Nowacek, Ari S.; Singh, Sangya; Balkundi, Shantanu; Rabinow, Barrett; McMillan, JoEllyn; Gendelman, Howard E; Kanmogne, Georgette D.

    2010-01-01

    Limitations inherent to antiretroviral therapy (ART) in its pharmacokinetic properties remain despite over 15 years of broad use. Our laboratory has pioneered a means to improve ART delivery through monocyte-macrophage carriage of nanoformulated drug-encapsulated particles (nanoART). To this end, our prior works sought to optimize nanoART size, structure, and physical properties for cell uptake and antiretroviral activities. To test the functional consequences of indinavir, ritonavir, and efa...

  9. Antiretroviral Treatment 2010: Progress and Controversies

    OpenAIRE

    Gulick, Roy M.

    2010-01-01

    Effective antiretroviral therapy (ART) changes the clinical course of HIV infection. There are 25 antiretroviral drugs approved for the treatment of HIV infection, and current antiretroviral drug regimens are highly effective, convenient, and relatively nontoxic. ART regimens should be chosen in consideration of a patient’s particular clinical situation. Successful treatment is associated with durable suppression of HIV viremia over years, and consequently, ART reduces the risk of clinical pr...

  10. Antiretroviral therapy: 'the state of the art'.

    Science.gov (United States)

    Montaner, J S; Montessori, V; Harrigan, R; O'Shaughnessy, M; Hogg, R

    1999-03-01

    The field of antiretroviral therapy is evolving at a very rapid pace. At this time, the initiation and optimization of antiretroviral therapy is based on serial plasma viral load determinations which aim to suppress viral replication to as low as possible for as long as possible, thus preventing disease progression. Currently available antiretrovirals require combination therapy with at least three agents to achieve this goal. Increasing availability of newer and more potent antiretroviral regimens will continue to enhance and simplify the number of therapeutic options available in the not too distant future. PMID:10337460

  11. Integration of Antiretroviral Therapy with Tuberculosis Treatment

    Science.gov (United States)

    Abdool Karim, Salim S.; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L.; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M.; Friedland, Gerald; Abdool Karim, Quarraisha

    2011-01-01

    Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; PIRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher. PMID:22010915

  12. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study

    Science.gov (United States)

    Caniglia, Ellen C.; Sabin, Caroline; Robins, James M.; Logan, Roger; Cain, Lauren E.; Abgrall, Sophie; Mugavero, Michael J.; Hernandez-Diaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard R.; 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; Olson, Ashley; Justice, Amy C.; Tate, Janet P.; Bucher, Heiner C.; Egger, Matthias; Touloumi, Giota; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

    2016-01-01

    Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9–12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9–12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question. PMID:26895294

  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. Testing anti-HIV activity of antiretroviral agents in vitro using flow cytometry analysis of CEM-GFP cells infected with transfection-derived HIV-1 NL4-3.

    Science.gov (United States)

    Frezza, Caterina; Grelli, Sandro; Federico, Maurizio; Marino-Merlo, Francesca; Mastino, Antonio; Macchi, Beatrice

    2016-06-01

    An assay, specifically optimized to evaluate the anti-HIV activity of antiretrovirals by flow cytometry analysis, is described. As widely used anti-HIV agents, zidovudine (AZT), abacavir (ABC), 2',3'-dideoxyinosine (DDI), lamivudine (3TC), nevirapine (NVP), and efavirenz (EFV), and as drugs of recent approval raltegravir (RAL), etravirine (ETR), and rilpivirine (RPV), were utilized as reference drugs. HIV-1 NL4-3 virus was prepared by transfection of HEK293T cells with purified plasmid DNA and quantified by p24 antigen-capture assay. For infection, CEM-GFP cells were exposed to vehicle or to several concentrations of the drugs for 2 hr at 37 °C before HIV-1 NL4-3 was added to each sample. The adsorption was prolonged for 3 hr at 37 °C. After 72 hr of incubation, HIV-induced GFP expression in infected CEM-GFP cells was assessed by flow cytometry analysis and expressed as % positive cells. For comparison, p24 production in supernatants was assessed by a commercial ELISA kit. On the basis of IC50 values, the anti-HIV activity, as assayed by this method, was EFV > 3TC > AZT > NVP > DDI > ABC and ETR > RPV > RAL. The comparison between the IC50 values calculated through flow cytometry and p24 production revealed overlapping results, showing that the optimized protocol of CEM-GFP infection with HIV NL4-3 is a suitable method to perform quantitative, rapid and low-expensive screening tests to evaluate the in vitro effect of new candidate anti-HIV drugs. PMID:26519867

  15. Antiretroviral Therapy in the Clinic▿

    OpenAIRE

    Tsibris, Athe M. N.; Hirsch, Martin S.

    2010-01-01

    Antiretroviral therapy in the developed world has resulted in substantial reductions in HIV-associated morbidity and mortality, changing an HIV diagnosis from a likely death sentence into a manageable chronic infection (F. J. Palella, Jr., K. M. Delaney, A. C. Moorman, M. O. Loveless, J. Fuhrer, G. A. Satten, D. J. Aschman, and S. D. Holmberg, N. Engl. J. Med. 338:853-860, 1998). Several million years of life have been saved by effective anti-HIV treatment, although these successes should not...

  16. 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; van Sighem, Ard;

    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.......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....

  17. 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...... and CD34 cells were measured. To examine the numbers of naive and memory type CD4 cells, CD4 cell coexpression of CD45RA and CD45RO was measured. Functionality of mobilized CD4 cells was examined by use of the proliferation assay and interleukin-2 ELISA. The number of CD34 cells increased from 1.50 to...... 20.01/microL (P < .002). The CD4 cell count increased from 236 to 452/microL (P < .002). The CD45RA/CD45RO ratio increased from 0.50 to 0.57 (P < .03). Mobilized CD4 cells were functionally intact. In conclusion, G-CSF induced increases in numbers of CD34 cells and CD4 cells in HIV-infected patients...

  18. The ARTμS: a novel microfluidic CD4+ T-cell enumeration system for monitoring antiretroviral therapy in HIV patients.

    Science.gov (United States)

    Liu, Qian; Chernish, Alexis; DuVall, Jacquelyn A; Ouyang, Yiwen; Li, Jingyi; Qian, Qiang; Bazydlo, Lindsay A L; Haverstick, Doris M; Landers, James P

    2016-02-01

    We report on a novel and cost-effective microfluidic platform that integrates immunomagnetic separation and cell enumeration via DNA-induced bead aggregation. Using a two-stage immunocapture microdevice, 10 μL of whole blood was processed to isolate CD4+ T-cells. The first stage involved the immuno-subtraction of monocytes by anti-CD14 magnetic beads, followed by CD4+ T-cell capture with anti-CD4 magnetic beads. The super hydrophilic surface generated during polydimethylsiloxane (PDMS) plasma treatment allowed for accurate metering of the CD4+ T-cell lysate, which then interacted with silica-coated magnetic beads under chaotropic conditions to form aggregates. Images of the resulting aggregates were captured and processed to reveal the mass of DNA, which was used to back-calculate the CD4+ T-cell number. Studies with clinical samples revealed that the analysis of blood within 24 hours of phlebotomy yielded the best results. Under these conditions, an accurate cell count was achieved (R(2) = 0.98) when compared to cell enumeration via flow cytometry, and over a functional dynamic range from 106-2337 cells per μL. PMID:26687070

  19. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    Science.gov (United States)

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care. PMID:27092564

  20. 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 ther

  1. Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

    DEFF Research Database (Denmark)

    Sharma, S; Babiker, A G; Emery, S; Gordin, F M; Lundgren, J D; Neaton, J N; Bakowska, E; Schechter, M; Wiselka, M J; Wolff, Mathias

    OBJECTIVES: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of...

  2. Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers

    Science.gov (United States)

    Chun, Tae-Wook; Shawn Justement, J.; Murray, Danielle; Kim, Connie J.; Blazkova, Jana; Hallahan, Claire W.; Benko, Erika; Costiniuk, Cecilia T.; Kandel, Gabor; Ostrowski, Mario; Kaul, Rupert; Moir, Susan; Casazza, Joseph P.; Koup, Richard A.; Kovacs, Colin; Fauci, Anthony S.

    2013-01-01

    Elite controllers suppress human immunodeficiency virus (HIV) viremia to below the limit of detection in the absence of antiretroviral therapy (ART). However, precise frequencies of CD4+ T cells carrying replication-competent HIV and/or the dynamics of the infectious viral reservoirs in response to initiation and discontinuation of ART in elite controllers are unknown. We show that the size of the pool of CD4+ T cells harboring infectious HIV diminished significantly after initiation of ART and rebounded to baseline upon cessation of therapy. Our data provide compelling evidence that persistent viral replication occurs in untreated elite controllers even in the absence of detectable plasma viremia. PMID:23847057

  3. Outcomes of Universal Access to Antiretroviral Therapy (ART) in Georgia

    OpenAIRE

    Carlos del Rio; Jack DeHovitz; Kenrad Nelson; Akaki Abutidze; Pati Gabunia; Natia Dvali; Otar Chokoshvili; Nikoloz Chkhartishvili; Lali Sharvadze; Tengiz Tsertsvadze

    2011-01-01

    Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm3. During followup, 152 (...

  4. The Survival Benefits of Antiretroviral Therapy in South Africa

    OpenAIRE

    April, Michael D; Wood, Robin; Berkowitz, Bethany K.; Paltiel, A David; Anglaret, Xavier; LOSINA, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2013-01-01

    Background.  We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods.  We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), secon...

  5. 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; Katlama, C; Chiesi, A; Goebel, F; Knysz, B; Antunes, F; Reiss, P; Lundgren, Jens Dilling

    2006-01-01

    BACKGROUND: It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) < 50 copies/ml]. OBJECTIVES: To compare the change in CD4 cell count over...... from starting cART, age, CD4 at first VL < 50 copies/ml, prior antiretroviral treatment, and change in CD4 cell count since starting cART. RESULTS: We studied 28418 instances of VL < 50 copies/ml in 4041 patients. The mean annual change in CD4 cell count was +45.5/microl [95% confidence interval (CI...

  6. Progress in antiretroviral drug delivery using nanotechnology

    OpenAIRE

    Rama Mallipeddi; Lisa Cencia Rohan

    2010-01-01

    Rama Mallipeddi, Lisa Cencia RohanUniversity of Pittsburgh, Department of Pharmaceutical Sciences, School of Pharmacy, Magee Womens Research Institute, Pittsburgh, PA, USAAbstract: There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatmen...

  7. 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....

  8. 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.

  9. 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

    , the predicted proportion of potential life-years survived was 83% with viral load monitoring (switch when viral load >500 copies per mL), 82% with CD4 cell count monitoring (switch at 50% drop from peak), and 82% with clinical monitoring (switch when two new WHO stage 3 events or a WHO stage 4 event occur...

  10. HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects na(i)ve to antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    XIAO Jian; LI Ming-yuan; WANG Ying; QIAN Ke-lei; CAO Qing-hua; QIU Chen-li; QIU Cao; XUE Yi-le; ZHANG Xiao-yan; ZHONG Ping; XU Jian-qing

    2011-01-01

    Background The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4+CD25+CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. ResultsCompared to HIV-1 seronegative donors, the levels of HLA-DR on CD4+CD25+CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163,P=0.004) and negatively with CD4 T-cell counts (r=-0.4153, P<0.0001). In addition, significant associations between HLA-DR expression on CD4+CD25+CD127lo/-Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4+ and CD8+ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.

  11. Inverse association between microRNA-124a and ABCC4 in HepG2 cells treated with antiretroviral drugs.

    Science.gov (United States)

    Nagiah, Savania; Phulukdaree, Alisa; Chuturgoon, Anil

    2016-09-01

    The ATP-binding cassette (ABC) super-family of drug transporters regulates efflux of xenobiotic compounds. The subfamily, multi-drug resistance proteins (MRPs) transports cyclic nucleotides and xenobiotics. Epigenetic modulation of drug transporters is scarcely described. The regulatory role of microRNA (miR)-124a on drug transporter gene ABCC4 was only recently reported. Our study investigated the differential regulation of miR-124a by nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine (AZT), Stavudine (d4T) and Tenofovir (TFV); at 24 h and 120 h treatments in HepG2 cells. ABCC4 mRNA (qPCR) and ABCC4 protein (western blot) were quantified. Cytotoxicity was evaluated by lactate dehydrogenase (LDH) levels. All NRTIs elevated miR-124a levels at 24 h, with a concomitant decline in ABCC4 mRNA levels (pdrugs have varying effects on miR-124a and ABCC4. PMID:26643107

  12. [Adhesion to the antiretroviral treatment].

    Science.gov (United States)

    Carballo, M

    2004-12-01

    The objective of the therapy antiretroviral is to improve the quality of life and the survival of the persons affected by the VIH through the suppression of the viral replication. Nevertheless one of the present problems is the resistant apparition of stumps to the new medicines caused by an incorrect management of the therapeutic plan; by an incorrect adhesion of the personal processing. Since the therapeutic success will depend, among others factors, and of important form of the degree of implication and commitment of the person affected, is a matter of identifying prematurely the possible situations concomitants (personal factors and of addiction, psycho-social, related to the processing and its possible secondary effects, associated factors to the own illness or even to the relation professional-patient) that can interfere in a correct adhesion. For it is necessary of the interaction multidisciplinary of the welfare team, and fundamental the work of nursing at the moment of to detect the possible determinant factors and the intervention definition of strategies arrived at by consensus with the own person, that they promote it or it improve. The quantification of the degree of adhesion (measure in %) values through various direct and indirect methods and should keep in mind in it takes of therapeutic decisions being able to come to be advised the suspension of the processing until obtaining to conscience to the person affected of the importance of a correct therapeutic compliance. PMID:15672996

  13. 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.

  14. Persistent HIV-1 replication during antiretroviral therapy

    Science.gov (United States)

    Martinez-Picado, Javier; Deeks, Steven G.

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community. Summary Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication. PMID:27078619

  15. 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...

  16. New antiretrovirals and new combinations.

    Science.gov (United States)

    Havlir, D V; Lange, J M

    1998-01-01

    The appearance in the clinic of two to three new antiretroviral agents yearly since 1995 has permitted unprecedented advances in HIV treatment. This remarkable pace of drug development is a testimony to an extraordinary international effort involving scientists, clinicians, governments, community activists and industry dedicated to the rapid and safe development of novel therapies. New drugs present the opportunity to improve HIV therapy. They also create an enormous challenge to the clinician, who must constantly assimilate data on new drugs and incorporate this information into practical management strategies. Combination therapy has proven the most effective approach to treat HIV disease. The profound and sustained viral suppression achievable with combinations such as indinavir (IDV), lamivudine (3TC) and zidovudine (ZDV) have resulted in a dramatic shift in HIV treatment paradigms over the last year. The full potential of combination therapy with available drugs has yet to be realized as only a limited number of the possible combinations incorporating new drugs have been fully tested. Even drugs available for many years may have untapped potential. Didanosine (ddI) and stavudine (d4T), once thought to be contraindicated in combination because of their overlapping peripheral neuropathy toxicity, have proven well tolerated and effective. Combination therapy can increase antiviral suppression, prevent drug resistance, optimize drug exposure and simplify dosing, but it can also result in pharmacologic antagonism, subtherapeutic drug concentrations and unexpected toxicities. Clinical studies have confirmed in vitro studies showing pharmacologic antagonism for the combination of ZDV and d4T. Combining protease inhibitors with each other or with non-nucleoside reverse transcriptase inhibitors is complicated by effects both classes of drugs have on drug metabolism and clearance. These observations underline the importance of carefully conducted clinical studies to

  17. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1

    Directory of Open Access Journals (Sweden)

    Sharma Akhilesh

    2009-12-01

    Full Text Available Abstract Background Combination antiretroviral (AR therapy continues to be the mainstay for HIV treatment. However, antiretroviral drug nonadherence can lead to the development of resistance and treatment failure. We have designed nanoparticles (NP that contain three AR drugs and characterized the size, shape, and surface charge. Additionally, we investigated the in vitro release of the AR drugs from the NP using peripheral blood mononuclear cells (PBMCs. Methods Poly-(lactic-co-glycolic acid (PLGA nanoparticles (NPs containing ritonavir (RTV, lopinavir (LPV, and efavirenz (EFV were fabricated using multiple emulsion-solvent evaporation procedure. The nanoparticles were characterized by electron microscopy and zeta potential for size, shape, and charge. The intracellular concentration of AR drugs was determined over 28 days from NPs incubated with PBMCs. Macrophages were imaged by fluorescent microscopy and flow cytometry after incubation with fluorescent NPs. Finally, macrophage cytotoxicity was determined by MTT assay. Results Nanoparticle size averaged 262 ± 83.9 nm and zeta potential -11.4 ± 2.4. AR loading averaged 4% (w/v. Antiretroviral drug levels were determined in PBMCs after 100 μg of NP in 75 μL PBS was added to media. Intracellular peak AR levels from NPs (day 4 were RTV 2.5 ± 1.1; LPV 4.1 ± 2.0; and EFV 10.6 ± 2.7 μg and continued until day 28 (all AR ≥ 0.9 μg. Free drugs (25 μg of each drug in 25 μL ethanol added to PBMCs served as control were eliminated by 2 days. Fluorescence microscopy and flow cytometry demonstrated phagocytosis of NP into monocytes-derived macrophages (MDMs. Cellular MTT assay performed on MDMs demonstrated that NPs are not significantly cytotoxic. Conclusion These results demonstrated AR NPs could be fabricated containing three antiretroviral drugs (RTV, LPV, EFV. Sustained release of AR from PLGA NP show high drug levels in PBMCs until day 28 without cytotoxicity.

  18. Impact of pharmaceutical care interventions on the CD4+ lymphocytes counts (therapeutic outcome of patients on antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Ezeudo Ewuziem Nwaozuzu

    2012-12-01

    Full Text Available CD4 count and viral load determine the progression of HIV infection. HIV actively infects and destroys CD4 cells. High viral load results in higher transmission risk and is also a sign of more severe disease. Measurements of CD4 counts can be used as an indirect means of estimating HIV viral load and as such determine disease progression and/or therapeutic outcome of antiretroviral therapy. Pharmaceutical care (PC has been shown to improve the outcome of drug therapy in many disease conditions. HIV/AIDS is one of the disease conditions that are fraught with many problems that can benefit from this new emphasis of pharmacy practice also known as ‘pharmacists care’. This study is designed to evaluate the impact of pharmaceutical care activities on the CD4 cell counts of HIV/AIDS patients receiving antiretroviral drugs. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care’ was used as a data collection instrument to evaluate, document and intervene and re-evaluate the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The results showed that that 55.2% of the patients recorded significant increases in their CD4 cells count, 14.1% of them maintained their pre - intervention CD4 cells count while 10.3% of them recorded decreases in their CD4 cell count. However, in 20.4% of the patients the CD4 cell counts could not be determined. The study showed that pharmacists’ interventions in antiretroviral drug therapy through Pharmaceutical care can significantly improve the CD4 cells counts of patients receiving antiretroviral drugs hence therapeutic outcome of antiretroviral drug therapy.

  19. [Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1].

    Science.gov (United States)

    Fukutake, Katsuyuki

    2015-11-01

    Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review]. PMID:26995879

  20. Pharmacodynamic and Antiretroviral Activities of Combination Nanoformulated Antiretrovirals in HIV-1–Infected Human Peripheral Blood Lymphocyte–Reconstituted Mice

    OpenAIRE

    Roy, Upal; McMillan, JoEllyn; Alnouti, Yazen; Gautum, Nagsen; Smith, Nathan; Balkundi, Shantanu; Dash, Prasanta; Gorantla, Santhi; Martinez-Skinner, Andrea; Meza, Jane; Kanmogne, Georgette; Swindells, Susan; Cohen, Samuel M.; Mosley, R. Lee; Poluektova, Larisa

    2012-01-01

    Lack of adherence, inaccessibility to viral reservoirs, long-term drug toxicities, and treatment failures are limitations of current antiretroviral therapy (ART). These limitations lead to increased viral loads, medicine resistance, immunocompromise, and comorbid conditions. To this end, we developed long-acting nanoformulated ART (nanoART) through modifications of existing atazanavir, ritonavir, and efavirenz suspensions in order to establish cell and tissue drug depots to achieve sustained ...

  1. Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

    OpenAIRE

    Koenig, Serena P; Bang, Heejung; Severe, Patrice; Jean Juste, Marc Antoine; Ambroise, Alex; Edwards, Alison; Hippolyte, Jessica; Fitzgerald, Daniel W; McGreevy, Jolion; Riviere, Cynthia; Marcelin, Serge; Secours, Rode; Warren D. Johnson; Pape, Jean W; Schackman, Bruce R.

    2011-01-01

    Editors' Summary Background AIDS has killed more than 25 million people since 1981, and about 33 million people (most of them living in low- and middle-income countries) are now infected with HIV, the virus that causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of infection. Then, in 1996, highly active antiretroviral ...

  2. Early and Late Direct Costs in a Southern African Antiretroviral Treatment Programme: A Retrospective Cohort Analysis

    OpenAIRE

    Leisegang, Rory; Cleary, Susan; Hislop, Michael; Davidse, Alistair; Regensberg, Leon; Little, Francesca; Maartens, Gary

    2009-01-01

    Editors' Summary Background About 30 million people (22 million people in sub-Saharan Africa alone) are infected with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS). HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, on average HIV-positive people died within 10 years of infection. Then, in 1996, highly active antiretroviral thera...

  3. D-dimer and CRP levels are elevated prior to antiretroviral treatment in patients who develop IRIS

    OpenAIRE

    Porter, Brian O.; Ouedraogo, G. Laissa; Hodge, Jessica; Smith, Margo; Pau, Alice; Roby, Gregg; Kwan, Richard; Bishop, Rachel; Rehm, Catherine; Mican, JoAnn; Sereti, Irini

    2010-01-01

    Biomarkers could be useful in evaluating immune reconstitution inflammatory syndrome (IRIS). A cohort of 45 HIV-1-infected, antiretroviral treatment (ART)-naïve patients with baseline CD4 T cell counts ≤100 cells/μL who were started on ART, suppressed HIV-RNA to

  4. Guidelines for antiretroviral therapy in adults

    Directory of Open Access Journals (Sweden)

    G Meintjes

    2012-09-01

    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.

  5. Adherence and Readiness to Antiretroviral Treatment

    OpenAIRE

    Södergård, Björn

    2006-01-01

    Antiretroviral therapy places extraordinarily high demands on adherence, since non-adherence affects both individuals and society due to the spread of resistant viral strains. The aims of the thesis were to investigate the prevalence of adherence in Swedish HIV-infected patients, changes in adherence over time, and factors associated with adherence, including patients’ readiness to adhere. Further, to investigate the collaboration between nurses, doctors and pharmacists after the introduction...

  6. Factors influencing global antiretroviral procurement prices

    OpenAIRE

    2009-01-01

    Background 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 g...

  7. The cost of antiretroviral therapy in Haiti

    OpenAIRE

    Fitzgerald Daniel W; Atwood Sidney; Severe Patrice; Leger Paul; Riviere Cynthia; Koenig Serena P; Pape Jean W; Schackman Bruce R

    2008-01-01

    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 treatme...

  8. Mortality and its predictors among antiretroviral therapy naïve HIV-infected individuals with CD4 cell count ≥350 cells/mm3 compared to the general population: data from a population-based prospective HIV cohort in Uganda

    Directory of Open Access Journals (Sweden)

    Ben Masiira

    2014-01-01

    Full Text Available Background: Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm3. Objective: To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm3 with mortality in the general Ugandan population and to investigate risk factors for death. Design: Population-based prospective HIV cohort. Methods: The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs. Results: A total of 374 participants with CD4 ≥350 cells/mm3 were followed for 1,328 person-years (PY over which 27 deaths occurred. Mortality rates (MRs (per 1,000 PY were 20.34 (95% CI: 13.95–29.66 among all participants and 16.43 (10.48–25.75 among participants aged 15–49 years. Mortality was higher in periods during which participants had CD4 350–499 cells/mm3 than during periods of CD4 ≥500 cells/mm3 although the difference was not statistically significant [adjusted rate ratio (aRR=1.52; 95% CI: 0.71–3.25]. Compared to the general Ugandan population aged 15–49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm3 (SMR: 223%, 95% CI: 127–393% and 146% higher among participants with CD4 350–499 cells/mm3 (246%, 117%–516. After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82–27.15 and decreasing body mass index (BMI (aRR comparing categories ≤17.4 Kg/m2 and ≥18.5 Kg/m2: 6.11, 2.30–16.20. Conclusion: HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm3 had a higher

  9. Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1

    OpenAIRE

    Nischang, Marc; Sutmuller, Roger; Gers-Huber, Gustavo; Audigé, Annette; Li, Duo; Rochat, Mary-Aude; Baenziger, Stefan; Hofer, Ursula; Schlaepfer, Erika; Regenass, Stephan; Amssoms, Katie; Stoops, Bart; Van Cauwenberge, Anja; Boden, Daniel; Kraus, Guenter

    2012-01-01

    BACKGROUND: Humanized mice generate a lymphoid system of human origin subsequent to transplantation of human CD34+ cells and thus are highly susceptible to HIV infection. Here we examined the efficacy of antiretroviral treatment (ART) when added to food pellets, and of long-acting (LA) antiretroviral compounds, either as monotherapy or in combination. These studies shall be inspiring for establishing a gold standard of ART, which is easy to administer and well supported by the mice, and for s...

  10. Effect of Antiretroviral Therapy on HIV-mediated Impairment of the Neutrophil Antimycobacterial Response

    Science.gov (United States)

    Bangani, Nonzwakazi; Goliath, Rene; Kampmann, Beate; Wilkinson, Katalin A.; Wilkinson, Robert J.; Martineau, Adrian R.

    2015-01-01

    Rationale: Experimental and epidemiological evidence suggests that neutrophils are important in the host response to tuberculosis. HIV infection, which increases the risk of tuberculosis, adversely affects neutrophil function. Objectives: To determine the impact of HIV and antiretroviral therapy on neutrophil antimycobacterial activity. Methods: We performed a cross-sectional comparison of neutrophil functions in 20 antiretroviral-naive HIV-infected and 20 HIV-uninfected individuals using luminescence-, flow cytometry–, and ELISA-based assays. We then conducted a prospective study in the HIV-infected individuals investigating these parameters during the first 6 months of antiretroviral therapy. Surface markers of neutrophil activation were investigated in a separate cohort using flow cytometry. Measurements and Main Results: HIV infection impaired control of Mycobacterium tuberculosis by neutrophils (mean ratio of mycobacterial luminescence in neutrophil samples vs. serum controls at 1 hour in HIV-infected participants, 0.88 ± 0.13 vs. HIV-uninfected participants, 0.76 ± 0.14; P = 0.01; at 24 hours, 0.82 ± 0.13 vs. 0.71 ± 0.13; P = 0.01). The extent of impairment correlated with log[HIV viral load]. Neutrophil cell death after 24 hours’ incubation with M. tuberculosis was higher in the HIV-infected cohort (85.3 ± 11.8% vs. 57.9 ± 22.4% necrotic cells; P < 0.0001). Neutrophils from HIV-infected participants demonstrated significantly more CD62L-negative cells (median, 23.0 vs. 8.5%; P = 0.008) and CD16-negative cells (3.2 vs. 1.3%, P = 0.03). Antiretroviral therapy restored mycobacterial restriction and pattern of neutrophil death toward levels seen in HIV-uninfected persons. Conclusions: Neutrophils in antiretroviral-naive HIV-infected persons are hyperactivated, eliminate M. tuberculosis less effectively than in HIV-uninfected individuals, and progress rapidly to necrotic cell death. These factors are

  11. Characteristics of HIV antiretroviral regimen and treatment adherence

    OpenAIRE

    2003-01-01

    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-demo...

  12. Cost analysis of antiretroviral agents available in India

    OpenAIRE

    Sagar S. Panchal; Prasad R. Pandit; Abhishek M. Phatak; Komal M. Lohi

    2015-01-01

    Background: AIDS is one of the most prevalent causes of death due to infectious origin which requires a lifelong therapy. There is variation in prices of antiretroviral drugs available in Indian market. Thus, a study was planned to find out variation in prices of antiretroviral drugs either as a single drug or in combination and to evaluate the difference in cost of various brands of the same antiretroviral drugs by calculating percentage variation in cost in Indian rupees. Methods: Cost o...

  13. Dosing antiretroviral medication when crossing time zones: a review.

    Science.gov (United States)

    Lewis, Joseph M; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye

    2016-01-01

    International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. PMID:26684823

  14. [Immunologic reconstruction after antiretroviral treatment].

    Science.gov (United States)

    Tubiana, R; Carcelain, G; Mohand, H A; Li, T S; Renaud, M; Blanc, C; Calvez, V; Debré, P; Agut, H; Katlama, C; Autran, B; Bricaire, F

    1999-02-27

    DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection. PMID:10093603

  15. 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

  16. Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial

    DEFF Research Database (Denmark)

    El-Sadr, W M; Grund, B; Neuhaus, J;

    2008-01-01

    BACKGROUND: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. OBJECTIVE: To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease or...... continuous therapy in participants previously assigned to episodic treatment. MEASUREMENTS: Opportunistic disease or death was the primary outcome. RESULTS: Eighteen months after the recommendation to reinitiate continuous therapy, mean CD4+ cell counts were 0.152 x 10(9) cells/L (95% CI, 0.136 to 0.167 x 10......(9) cells/L) less in participants previously assigned to episodic treatment (P < 0.001). The proportion of follow-up time spent with CD4+ cell counts of 0.500 x 10(9) cells/L or more and HIV RNA levels of 400 copies/mL or less was 29% for participants initially assigned to episodic therapy and 66% for those...

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

    OpenAIRE

    Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L; Gerstoft, Jan; Sisse R Ostrowski

    2013-01-01

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

  18. Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries

    OpenAIRE

    Avila, Dorita; Keri N Althoff; Mugglin, Catrina; Wools-Kaloustian, Kara; Koller, Manuel; Dabis, François; Nash, Denis; Gsponer, Thomas; Sungkanuparph, Somnuek; McGowan, Catherine; May, Margaret; Cooper, David; Chimbetete, Cleophas; Wolff, Marcelo; Collier, Ann

    2014-01-01

    OBJECTIVE To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were...

  19. Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study

    OpenAIRE

    Tavel, Jorge A.; Abdel Babiker; Lawrence Fox; Daniela Gey; Gustavo Lopardo; Norman Markowitz; Nicholas Paton; Deborah Wentworth; Nicole Wyman

    2010-01-01

    BACKGROUND: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4(+) counts compared to no therapy. METHODOLOGY: Participants not on continuous ART with > or = 300 CD4(+) cells/mm(3) were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2...

  20. Pharmacodynamic and Antiretroviral Activities of Combination Nanoformulated Antiretrovirals in HIV-1–Infected Human Peripheral Blood Lymphocyte–Reconstituted Mice

    Science.gov (United States)

    Roy, Upal; McMillan, JoEllyn; Alnouti, Yazen; Gautum, Nagsen; Smith, Nathan; Balkundi, Shantanu; Dash, Prasanta; Gorantla, Santhi; Martinez-Skinner, Andrea; Meza, Jane; Kanmogne, Georgette; Swindells, Susan; Cohen, Samuel M.; Mosley, R. Lee; Poluektova, Larisa; Gendelman, Howard E.

    2012-01-01

    Lack of adherence, inaccessibility to viral reservoirs, long-term drug toxicities, and treatment failures are limitations of current antiretroviral therapy (ART). These limitations lead to increased viral loads, medicine resistance, immunocompromise, and comorbid conditions. To this end, we developed long-acting nanoformulated ART (nanoART) through modifications of existing atazanavir, ritonavir, and efavirenz suspensions in order to establish cell and tissue drug depots to achieve sustained antiretroviral responses. NanoART's abilities to affect immune and antiviral responses, before or following human immunodeficiency virus type 1 infection were tested in nonobese severe combined immune-deficient mice reconstituted with human peripheral blood lymphocytes. Weekly subcutaneous injections of drug nanoformulations at doses from 80 mg/kg to 250 mg/kg, 1 day before and/or 1 and 7 days after viral exposure, elicited drug levels that paralleled the human median effective concentration, and with limited toxicities. NanoART treatment attenuated viral replication and preserved CD4+ Tcell numbers beyond that seen with orally administered native drugs. These investigations bring us one step closer toward using long-acting antiretrovirals in humans. PMID:22811299

  1. Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation

    OpenAIRE

    Grant, Philip M.; Kitch, Douglas; McComsey, Grace A; Dube, Michael P.; Haubrich, Richard; Huang, Jeannie; Riddler, Sharon; Tebas, Pablo; Zolopa, Andrew R.; Collier, Ann C; Brown, Todd T.

    2013-01-01

    Low pretreatment CD4+ cell count is an independent risk factor for bone loss after antiretroviral therapy (ART) initiation, providing further evidence for the benefits of early ART. Initiation of ART at higher CD4+ counts may reduce the burden of osteoporosis and fragility fracture.

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

    DEFF Research Database (Denmark)

    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...

  3. Emergence of HIV-1 drug resistance mutations among antiretroviral-naïve HIV-1-infected patients after rapid scaling up of antiretroviral therapy in Thailand

    Directory of Open Access Journals (Sweden)

    Sungkanuparph Somnuek

    2012-03-01

    Full Text Available Abstract Background After rapid scaling up of antiretroviral therapy in HIV-1-infected patients, the data of primary HIV-1 drug resistance in Thailand is still limited. This study aims to determine the prevalence and associated factors of primary HIV-1 drug resistance in Thailand. Methods A prospective observational study was conducted among antiretroviral-naïve HIV-1-infected Thai patients from 2007 to 2010. HIV-1 subtypes and mutations were assayed by sequencing a region of HIV-1 pol gene. Surveillance drug resistance mutations recommended by the World Health Organization for surveillance of transmitted HIV-1 drug resistance in 2009 were used in all analyses. Primary HIV-1 drug resistance was defined as the presence of one or more surveillance drug resistance mutations. Results Of 466 patients with a mean age of 38.8 years, 58.6% were males. Risks of HIV-1 infection included heterosexual (77.7%, homosexual (16.7%, and intravenous drug use (5.6%. Median (IQR CD4 cell count and HIV-1 RNA were 176 (42-317 cells/mm3 and 68,600 (19,515-220,330 copies/mL, respectively. HIV-1 subtypes were CRF01_AE (86.9%, B (8.6 and other recombinants (4.5%. The prevalence of primary HIV-1 drug resistance was 4.9%; most of these (73.9% had surveillance drug resistance mutations to only one class of antiretroviral drugs. The prevalence of patients with NRTI, NNRTI, and PI surveillance drug resistance mutations was 1.9%, 2.8% and 1.7%, respectively. From logistic regression analysis, there was no factor significantly associated with primary HIV-1 drug resistance. There was a trend toward higher prevalence in females [odds ratio 2.18; 95% confidence interval 0.896-5.304; p = 0.086]. Conclusions There is a significant emergence of primary HIV-1 drug resistance in Thailand after rapid scaling up of antiretroviral therapy. Although HIV-1 genotyping prior to antiretroviral therapy initiation is not routinely recommended in Thailand, our results raise concerns about the

  4. Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs

    DEFF Research Database (Denmark)

    Kolte, L.; Gaardbo, J.C.; Skogstrand, Kristin;

    2008-01-01

    Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores...... if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38......(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly...

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

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C; Vella, S; Zilmer, K; Kjær, Jesper; Knysz, B; Phillips, AN; Mocroft, A; Lundgren, Jens Dilling

    2006-01-01

    BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western...... 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......, observational cohort with 11,928 HIV-1-infected patients. METHODS: Response to cART was analysed in patients with subtypes determined pre-cART, via multivariable logistic regression on the first measurements 6–12 months after starting cART. A virological response was defined as a viral load <500 copies/ml and...

  6. The Impact of Antiretroviral Therapy on Lung Immunology.

    Science.gov (United States)

    Cribbs, Sushma K; Fontenot, Andrew P

    2016-04-01

    Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV. PMID:26974295

  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. 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.

  9. Expansion of China's free antiretroviral treatment program

    Institute of Scientific and Technical Information of China (English)

    ZHAO De-cai; ZHANG Fu-jie; WEN Yi; MA Ye; ZHAO Yan; ZHANG Yao; WU Ya-song; LIU Xia; Elizabeth Au; LIU Zhong-fu

    2012-01-01

    Background In 2003,China's National Free Antiretroviral Treatment Program (NFATP) was initiated as a pilot,which covered only 100 HIV/AIDS patients.By 2011,the pilot had evolved into a nationwide program and had provided free treatment for over 150 000 patients.The objective of this study was to report and evaluate the progress of China's free antiretroviral treatment program.Methods The NFATP Database was systematically reviewed and a total of 150 692 HIV/AIDS patients were included in this study.Program progress indicators including the number of treated HIV/AIDS patients,follow-up visit rate,CD4 test rate,and viral load test rate were summarized and examined over a calendar year to evaluate the progress of NFATP quantitatively and qualitatively.Results By the end of 2011,a total of 150 692 HIV/AIDS patients had been treated through the NFATP and 122 613 of them were still on treatment.Of all patients,about 72% were enrolled during the past four years.The dominant transmission route was blood related in the early phase of the NFATP,but gradually changed to sexual contact.Besides quantitative improvements,progress indicators also demonstrated significant qualitative improvements that the program had made during the past 9 years.Conclusions Great achievement has been made by China's NFATP.China's experience indicates the importance of a comprehensive response to the success of its treatment program.However,to ensure the quality and sustainability of treatment in the long term,more attention and resources should be paid towards program management.Chin Med J 2012; 125(19):3514-3521

  10. When to start antiretroviral therapy: the need for an evidence base during early HIV infection

    OpenAIRE

    Lundgren, J D; Babiker, A. G.; Gordin, F. M.; Borges, A.; Neaton, J D

    2013-01-01

    Background 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 remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count h...

  11. Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modelling Study

    OpenAIRE

    Timothy B Hallett; Baeten, Jared M.; Renee Heffron; Ruanne Barnabas; Guy de Bruyn; Íde Cremin; Sinead Delany; Garnett, Geoffrey P; Glenda Gray; Leigh Johnson; James McIntyre; Helen Rees; Connie Celum

    2011-01-01

    Editors' Summary Background Every year, about 2.5 million people become infected with HIV, the virus that causes AIDS. HIV is usually transmitted through unprotected sex with an HIV-infected partner. It destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. There is no cure for AIDS, although HIV can be held in check with antiretroviral therapy (ART), and there is no vaccine that protects against HIV infection. S...

  12. 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...

  13. Activity of antiretroviral drugs in human infections by opportunistic agents

    OpenAIRE

    Izabel Galhardo Demarchi; Daniela Maira Cardozo; Sandra Mara Alessi Aristides; Ricardo Alberto Moliterno; Thaís Gomes Verzignassi Silveira; Rosilene Fressatti Cardoso; Dennis Armando Bertolini; Terezinha Inez Estivalet Svidzinski; Jorge Juarez Vieira Teixeira; Maria Valdrinez Campana Lonardoni

    2012-01-01

    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 ...

  14. Current Perspectives on HIV-1 Antiretroviral Drug Resistance

    OpenAIRE

    Pinar Iyidogan; Anderson, Karen S.

    2014-01-01

    Current advancements in antiretroviral therapy (ART) have turned HIV-1 infection into a chronic and manageable disease. However, treatment is only effective until HIV-1 develops resistance against the administered drugs. The most recent antiretroviral drugs have become superior at delaying the evolution of acquired drug resistance. In this review, the viral fitness and its correlation to HIV-1 mutation rates and drug resistance are discussed while emphasizing the concept of lethal mutagenesis...

  15. Adherence to antiretroviral therapy among people living with HIV

    Directory of Open Access Journals (Sweden)

    Basavaprabhu Achappa

    2013-01-01

    Full Text Available Background: Acquired immune deficiency syndrome (AIDS is now considered as a manageable chronic illness. There has been a dramatic reduction in human immunodeficiency virus (HIV related morbidity and mortality due to antiretroviral therapy. A high level of adherence (>95% is required for antiretroviral therapy to be effective. There are many barriers to adherence in both developed and developing countries. Aim: The aim of our study was to determine adherence levels and factors influencing adherence to antiretroviral therapy among people living with HIV. Materials and Methods: Using a cross-sectional study design, 116 HIV positive patients receiving antiretroviral therapy for at least 1 year were interviewed using a semi structured questionnaire. The collected data was analyzed using Statistical Product and Service Solutions (SPSS version 11.5. Chi-square test was done. A P value of < 0.05 was considered statistically significant. Results: Of 116 participants, 63.7% reported adherence ≥ 95%. Mean adherence index was 91.25%. Financial constraints, forgetting to take medication, lack of family care, depression, alcohol use, social stigma and side effects to antiretroviral therapy were barriers for adherence in our study. Conclusion: Adherence to antiretroviral therapy in south India is suboptimal. Intensive adherence counseling should be provided to all patients before initiation ofantiretroviral therapy. Health care providers must identify possible barriers to adherence at the earliest and provide appropriate solutions.

  16. 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

    Full Text Available BACKGROUND: 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 NCT00125099 METHODS: Twenty 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. RESULTS: 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. CONCLUSIONS: 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

  17. Antiretroviral treatment of HIV infection: Swedish recommendations 2007.

    Science.gov (United States)

    Josephson, Filip; Albert, Jan; Flamholc, Leo; Gisslén, Magnus; Karlström, Olof; Lindgren, Susanne-Rosa; Navér, Lars; Sandström, Eric; Svedhem-Johansson, Veronica; Svennerholm, Bo; Sönnerborg, Anders

    2007-01-01

    On 3 previous occasions, in 2002, 2003 and 2005, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. An expert group, under the guidance of RAV, has now revised the text again. Since the publication of the previous treatment recommendations, 1 new drug for the treatment of HIV has been approved - the protease inhibitor (PI) darunavir (Prezista). Furthermore, 3 new drugs have become available: the integrase inhibitor raltegravir (MK-0518), the CCR5-inhibitor maraviroc (Celsentri), both of which have novel mechanisms of action, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (TMC-125). The new guidelines differ from the previous ones in several respects. The most important of these are that abacavir is now preferred to tenofovir and zidovudine, as a first line drug in treatment-naïve patients, and that initiation of antiretroviral treatment is now recommended before the CD4 cell count falls below 250/microl, rather than 200/microl. Furthermore, recommendations on the treatment of HIV infection in children have been added to the document. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels). PMID:17577810

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

    Directory of Open Access Journals (Sweden)

    Dominique J Pepper

    Full Text Available BACKGROUND: 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. METHOD: 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. FINDINGS: 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. CONCLUSION: 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.

  19. 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.

    OpenAIRE

    Gomez, G.B.; Venter, W. D. F.; Lange, J.M.A.; H. Rees; 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 clinical trials. Demonstration projects are needed to evaluate "real world" programme effectiveness. We present the protocol for a demonstration study to evaluate the feasibility, acceptability, and co...

  20. HIV Antiretroviral Resistance Mutations Among Antiretroviral Treatment-Naive and -Experienced Patients in South Korea

    OpenAIRE

    Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Kim, Yong Chan; Oh, Dong Hyun; Choi, Heun; Ann, Hea Won; Kim, Jae Kyoung; Kim, Sun Bean; Jeong, Su Jin; Ku, Nam Su; Han, Sang Hoon; Song, Young Goo; Kim, June Myung; Choi, Jun Yong

    2013-01-01

    The purpose of this study was to assess the prevalence and characteristics of HIV drug resistance mutations among antiretroviral therapy (ART)-naive and ART-experienced patients in South Korea. A total of 50 ART-naive and 34 ART-experienced Korean HIV-1-infected patients who visited an urban hospital from February 2007 to March 2011 were included. Most patients (86.9%) were infected with clade B HIV-1. Six (12%) ART-naive and 22 (64.7%) ART-experienced patients had HIV strains with resistance...

  1. Approaches to antiretroviral therapy in China

    Institute of Scientific and Technical Information of China (English)

    Bruce L GILLIAM; Robert R REDFIELD

    2005-01-01

    China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment (ART)program. However, high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide. Concepts which will define treatment success and local and national programmatic goals are 1) access to ART, 2) durability of ART at the patient level, 3)scalability of treatment modalities, and the 4) sustainability of the program at the community or national level. In the face of limited resources, China must also consider when to start ARV therapy, which agents to use, when to switch them, and how to treat highly experienced patients with drug resistance. The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data. Currently, a regimen including tenofovir, emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV/AIDS in China. However, critical to all of these choices is the evaluation of programs implemented to insure wide scale success. China has wisely begun this process of evaluating the performance of local programs through systematic monitoring and evaluation of treatment outcomes. This will allow regimens and programs that work to be expanded, and programs with high failure rates to be eliminated. In the end,evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences

  2. 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. PMID:25310145

  3. Impact of antiretroviral therapy on pregnancy outcomes

    Directory of Open Access Journals (Sweden)

    C D Aniji

    2013-12-01

    Full Text Available Background.The majority of HIV-positive women in South Africa are of reproductive age, and pregnancies among women using antiretroviral therapy (ART are common. However, there are mixed data regarding the impact of ART on pregnancy outcomes.Objective. To examine the impact of ART on pregnancy outcome according to the timing of initiation of treatment.Methods. A retrospective cohort study was conducted among women delivering at a tertiary hospital from 1 October 2008 to 31 March 2009.Results. A total of 245 mothers were receiving ART: 76 mothers (31% started ART pre-conception and 169 mothers (69% started ART after the first trimester. No significant differences were observed in the rates of preterm delivery and low birth weight (LBW between the pre- and post-conception groups (21% v. 24% and 21% v. 25%, respectively.Conclusion. In this cohort of women receiving ART in pregnancy, timing of ART initiation did not have any adverse effect on the measured pregnancy outcomes such as preterm delivery and LBW.

  4. Long-term use of first-line highly active antiretroviral therapy is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients

    Directory of Open Access Journals (Sweden)

    Haohui Zhu

    2014-09-01

    Full Text Available Objective: To evaluate whether or not highly active antiretroviral therapy is associated with carotid artery stiffness in human immunodeficiency virus-positive patients in Henan Province, China. Method: Fifty human immunodeficiency virus-positive patients with at least a 5-year history of highly active antiretroviral therapy use and 50 human immunodeficiency virus-positive patients without a history of highly active antiretroviral therapy use were enrolled in this study. Carotid artery intima-media thickness and stiffness were determined by quantitative inter-media thickness and quantitative artery stiffness, respectively. Results: No statistically significant difference in carotid artery intima-media thickness and stiffness was observed between groups. A significant association between human immunodeficiency virus infection time and carotid artery stiffness was observed, but no significant association between human immunodeficiency virus infection time and intima-media thickness was found. No significant association between intima-media thickness, stiffness, and CD4+ and CD8+ T-cell counts were observed. Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.

  5. Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa

    OpenAIRE

    Haberer, Jessica E.; Baeten, Jared M; Campbell, James; Wangisi, Jonathan; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Psaros, Christina; Safren, Steven A.; Ware, Norma C.; Thomas, Katherine K.; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Celum, Connie

    2013-01-01

    Editors' Summary Background Every year, about 2.5 million people (mostly living in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. HIV, which is usually transmitted through unprotected sex with an HIV-infected partner, destroys immune system cells, leaving infected individuals susceptible to other infections. There is no cure for AIDS, although antiretroviral drugs can hold HIV in check, and there is no vaccine against HIV infection. Individuals can reduce their risk...

  6. Correlates of Unstructured Antiretroviral Treatment Interruption in a Cohort of HIV-Positive Individuals in British Columbia

    OpenAIRE

    Samji, Hasina; Chen, Yalin; Salters, Kate; Montaner, Julio S.G.; Hogg, Robert S.

    2014-01-01

    Treatment interruptions (TIs) limit the therapeutic success of combination antiretroviral therapy and are associated with higher morbidity and mortality. HIV-positive individuals dealing with concurrent health issues, access challenges and competing life demands are hypothesized to be more likely to interrupt treatment. Individuals were included if they initiated cART ≥1 year prior to interview date and had a CD4 cell count or initial regimen recorded at initiation. Using pharmacy recording, ...

  7. Quality of life of people living with HIV, preliminary results from IANUA (Investigation on Antiretroviral Therapy) study

    OpenAIRE

    Alberto Venturini; Barbara Giannini; Marcello Montefiori; Antonio Di Biagio; Giovanni Mazzarello; Giovanni Cenderello; Mauro Giacomini; Caterina Merlano; Patrizia Orcamo; Maurizio Setti; Claudio Viscoli; Giovanni Cassola

    2014-01-01

    Introduction: The introduction of combined antiretroviral treatment (cART) has reduced HIV-associated morbidity and mortality, and changed the patients’ perspective of life. As a result, Health Related Quality of Life (HRQOL) has become a crucial clinical issue. Objective: Assessment of HRQOL in a sample of Italian patients from IANUA study. Investigate correlation between CD4 cell counts, viral load and changes in HRQOL. Materials and Methods: EQ-5D-3L self-reported q...

  8. Immune reconstitution inflammatory syndrome in HIV-infected patients receiving antiretroviral therapy : pathogenesis, clinical manifestations and management

    DEFF Research Database (Denmark)

    Dhasmana, Devesh J; Dheda, Keertan; Ravn, Pernille;

    2008-01-01

    The use of antiretroviral therapy (ART) to treat HIV infection, by restoring CD4+ cell count and immune function, is associated with significant reductions in morbidity and mortality. Soon after ART initiation, there is a rapid phase of restoration of pathogen-specific immunity. In certain patients...... patients who are severely affected. In this review, we discuss research relating to pathogenesis, the range of clinical manifestations, treatment options and prevention issues....

  9. Impact of Hepatitis C Virus Coinfection on Response to Highly Active Antiretroviral Therapy and Outcome in HIV-Infected Individuals: A Nationwide Cohort Study

    DEFF Research Database (Denmark)

    Lindhardt, Bjarne Ø.; Kronborg, Gitte; Hansen, Ann-Brit E.;

    2006-01-01

    BACKGROUND: Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among...... <0.3, from acquired immunodeficiency syndrome-related disease, and if they had a history of alcohol abuse. Although we observed no difference in viral load between the HCV-positive and HCV-negative groups, the HCV-positive group had a marginally lower absolute CD4+ cell count. CONCLUSIONS: HIV...

  10. 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.

  11. 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; Colebunders, Robert; van Lunzen, Jan; Podlekareva, Daria; Hansen, Ann-Brit Eg; Machala, Ladislav; Yust, Israel; Benfield, Thomas; NN, NN

    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...

  12. 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 A.C.); 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 antiretr

  13. 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 functi...

  14. The Place of protease inhibitors in antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    S.B. Tenore

    2009-10-01

    Full Text Available With the introduction of highly active antiretroviral therapy, a number of drugs have been developed. The best choice concerning which antiretroviral analogs to start is always under discussion, especially in the choice between non-nucleoside reverse transcriptase inhibitors-based therapies and ritonavir-boosted protease inhibitors. Both are proven to control viral replication and lead to immunological gain. The choice between a non-nucleoside analog reverse transcriptase inhibitor and a protease inhibitor as a third antiretroviral drug in the therapy should consider factors related to the individual, as well as the inclusion of the best therapy in the patient's daily activities and potential adherence. The protease inhibitor-based therapies showed similar efficacy among the various inhibitors with characteristics concerning the adverse events from each medicine. For the treatment of protease-resistant patients, darunavir and tipranavir showed good efficacy with higher genetic barrier to resistance.

  15. Efeitos das drogas anti-retrovirais sobre o metabolismo glicídico e células de Langerhans de pâncreas de ratas Wistar prenhes Effects of antiretroviral drugs on glucide metabolism and pancreatic Langerhans' cells of pregnant Wistar rats

    Directory of Open Access Journals (Sweden)

    Ernesto Antonio Figueiró-Filho

    2004-06-01

    nelfinavir were administered to the animals at doses 10 times higher than those administered to pregnant women. The animals were divided into seven groups of 10 animals, including a control group. The animals were sacrificed on the 21st day of pregnancy and glycemia, insulinemia, glucagonemia, free fatty acids (FFA and hepatic glycogen were measured. Direct counts of the number of immunohistochemically labeled insulin- and glucagon-producing cells were used to determine pancreatic damage. Data were analyzed statistically by the Student's t-test comparing each treated group with the control group. RESULTS: increased serum glucagon (control group: 88.2 pg/ml; treated groups: 99.7-120.7 pg/ml and reduced insulin (control group: 6.2 muIU/ml; treated groups: 2.1-2.7 muIU/ml were observed in all groups treated with antiretroviral drugs after 21 days of pregnancy. There was no significant difference between the experimental groups and the control in glycemia, plasma FFA or hepatic glycogen. Also, there was no significant difference in number of insulin- and glucagon-producing cells between the treated groups and the control. CONCLUSION: treatment of noninfected rats with antiretroviral drugs during pregnancy altered maternal glycid metabolism causing insulin decrease and glucagon elevation, with normal glycemia and unchanged number of pancreatic cells.

  16. Pericardial effusion of HIV-infected patients - results of a prospective multicenter cohort study in the era of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Lind A

    2011-11-01

    Full Text Available Abstract Background Patients with human immunodeficiency virus (HIV infection have an increased risk of cardiovascular diseases. Previous publications described pericardial effusion as one of the most common HlV-associated cardiac affiliations. The aim of the current study was to investigate if pericardial effusion still has a relevant meaning of HIV-infected patients in the era of antiretroviral therapy. Methods The HIV-HEART (HIV-infection and HEART disease study is a cardiology driven, prospective and multicenter cohort study. Outpatients with a known HIV-infection were recruited during a 20 month period in a consecutive manner from September 2004 to May 2006. The study comprehends classic parameters of HIV-infection, comprising CD4-cell count (cluster of differentiation and virus load, as well as non-invasive tests of cardiac diseases, including a thorough transthoracic echocardiography. Results 802 HIV-infected patients (female: 16.6% with a mean age of 44.2 ± 10.3 years, were included. Duration of HIV-infection since initial diagnosis was 7.6 ± 5.8 years. Of all participants, 85.2% received antiretroviral therapy. Virus load was detectable in 34.4% and CD4 - cell count was in 12.4% less than 200 cells/μL. Pericardial effusions were present in only two patients of the analysed population. None of the participants had signs of a relevant cardiovascular impairment by pericardial effusion. Conclusions Our results demonstrate that the era of antiretroviral therapy goes along with low rates of pericardial effusions in HIV-infected outpatients. Our findings are in contrast to the results of publications, performed before the common use of antiretroviral therapy.

  17. 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

  18. Adherence to antiretroviral therapy: are we doing enough?

    Science.gov (United States)

    Read, T; Mijch, A; Fairley, C K

    2003-01-01

    Adherence to antiretroviral therapy is a powerful predictor of response to therapy. For optimal antiretroviral therapy response, individuals need to take more than 95% of their prescribed medication. The most widely used method for measuring adherence is self-report of the number of missed doses and this should be done at every clinic visit. There are several well-recognized predictors of poor adherence, such as illicit drug use, depression, limited knowledge or ambivalence about starting treatment. Adherence can be improved by addressing these issues or through other means such as pill boxes or electronic reminders. PMID:12752896

  19. 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.

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

    OpenAIRE

    Valerie J. Ehlers; Esther Kip; Van der Wal, Dirk M.

    2009-01-01

    Anti-retroviral drugs (ARVs) are supplied free of charge in Botswana. Lifelong adherence to anti-retroviral therapy (ART) is vital to improve the patient’s state of well-being and to prevent the development of strains of the human immunodef ciency virus (HIV) that are resistant to ART. Persons with ART-resistant strains of HIV can spread these to other people, requiring more expensive ART with more severe side-effects and poorer health outcomes. The purpose of this exploratory, descriptive, q...

  1. Effectiveness and Safety of Concurrent Use of First-Line Antiretroviral and Antituberculous Drugs in Rwanda

    Directory of Open Access Journals (Sweden)

    Justin Ntokamunda Kadima

    2014-01-01

    Full Text Available Background. Overlapping toxicity between drugs used for HIV and TB could complicate the management of HIV/TB coinfected patients, particularly those carrying multiple opportunistic infections. This study aimed to evaluate the clinical outcomes and adverse drug events in HIV patients managed with first-line antiretroviral and first-line anti-TB drugs. Methods. This is a retrospective study utilizing medical dossiers from single-HIV infected and HIV/TB coinfected patients already initiated on ART. Predictors of outcomes included changes in CD4 cells/mm3, body weight, physical improvement, death rate, and adverse drug reactions. Results. Records from 60 HIV patients and 60 HIV/TB patients aged between 20 and 58 years showed that all clinical indicators of effectiveness were better in single-HIV infected than in HIV/TB coinfected patients: higher CD4 cell counts, better physical improvement, and low prevalence of adverse drug events. The most frequently prescribed regimen was TDF/3TC/EFV+RHZE. The mortality rate was 20% in HIV/TB patients compared to 8.3% in the single-HIV group. Conclusion. Treatment regimens applied are efficient in controlling the progression of the infection. However, attention should be paid to adjust dosing when combining nonnucleoside antiretrovirals (EFV and NVR with anti-TB drugs to minimize the risk of death by drug intoxication.

  2. The Effects Of Antiretroviral Drugs On The Absorbance Characteristics Of Blood Components

    Directory of Open Access Journals (Sweden)

    O. I. Ani

    2015-08-01

    Full Text Available Abstract The effects of antiretroviral drugs on the absorbance characteristics of blood components have been studied. The methodology involved the serial dilution of the five different antiretroviral drugs two HAARTFDC and three single drugs and the subsequent incubation with the blood samples collected from ten blood samples of HIV negative persons for the absorbance measurement using a digital Ultraviolet Visible MetaSpecAE1405031Pro Spectrophotometer. Reflectance Dielectric constant etc were derived from the absorbance data. For these drugs to be effective as HIV blockers they should be able to coat the surfaces of the lymphocytes. The question therefore arises as to what extent these drugs are able to coat the surfaces of the blood cells This was established using the extent of absorbance change. Models for coating effectiveness were formulated. The coating effectiveness was therefore calculated from peak absorbance values. Red blood cells were shown not to give reliable results. The results obtained however establish the fact that some coating of the drug had really occurred on the surfaces of the lymphocytes. The drug films were determined for lymphocytes and used to explain some observed clinical findings. The use of the findings of this work in drug design may be expected to yield good results.

  3. Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Bo He

    2013-04-01

    Full Text Available Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%. Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p < 0.001 and persistently lower CD4+ cell count (p < 0.001 compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4+ cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy.

  4. Stealth anti-CD4 conjugated immunoliposomes with dual antiretroviral drugs--modern Trojan horses to combat HIV.

    Science.gov (United States)

    Ramana, Lakshmi Narashimhan; Sharma, Shilpee; Sethuraman, Swaminathan; Ranga, Udaykumar; Krishnan, Uma Maheswari

    2015-01-01

    Highly active antiretroviral therapy (HAART) is the currently employed therapeutic intervention against AIDS where a drug combination is used to reduce the viral load. The present work envisages the development of a stealth anti-CD4 conjugated immunoliposomes containing two anti-retroviral drugs (nevirapine and saquinavir) that can selectively home into HIV infected cells through the CD4 receptor. The nanocarrier was characterized using transmission electron microscopy, FTIR, differential scanning calorimetry, particle size and zeta potential. The cell uptake was also evaluated qualitatively using confocal microscopy and quantitatively by flow cytometry. The drug to lipid composition was optimized for maximum encapsulation of the two drugs. Both drugs were found to localize in different regions of the liposome. The release of the reverse transcriptase inhibitor was dominant during the early phases of the release while in the later phases, the protease inhibitor is the major constituent released. The drugs delivered via anti-CD4 conjugated immunoliposomes inhibited viral proliferation at a significantly lower concentration as compared to free drugs. In vitro studies of nevirapine to saquinavir combination at a ratio of 6.2:5 and a concentration as low as 5 ng/mL efficiently blocked viral proliferation suggesting that co-delivery of anti-retroviral drugs holds a greater promise for efficient management of HIV-1 infection. PMID:25500283

  5. The naive CD4+ count in HIV-1-infected patients at time of initiation of highly active antiretroviral therapy is strongly associated with the level of immunological recovery

    DEFF Research Database (Denmark)

    Michael, OG; Kirk, O; Mathiesen, Lars Reinhardt;

    2002-01-01

    Current antiretroviral therapy can induce considerable, sustained viral suppression followed by immunological recovery, in which naive CD4 + cells are important. Long-term immunological recovery was investigated during the first 3 y of highly active antiretroviral therapy (HAART) in 210 HIV-1...... immunological recovery that can be obtained from treatment. Surprisingly, the naive CD4 + cell count tended to stabilize at a subnormal level after 18 months of HAART. This finding merits further investigation.......-infected patients. The focus was on the naive CD4 + cell time course and associations between naive CD4 + cell counts and established prognostic markers. Total and naive CD4 + cell counts were measured using flow cytometry. The HIV-RNA detection limit was 20 copies/ml. During 36 months of HAART, the total...

  6. 人类免疫缺陷病毒1型慢性感染者B细胞表型分析及抗反转录病毒治疗的修复作用%Analysis of B cell phenotype and the restoration of antiretroviral therapy in chronic human immunodeficiency virus type 1 infection

    Institute of Scientific and Technical Information of China (English)

    闫静静; 仇超; 李亮助; 邱趁丽; 傅卫辉; 孙俊; 徐建青; 张晓燕

    2013-01-01

    patients were significantly lower than that in the healthy controls ,but could be restored by antiretroviral therapy (ART) . The decline of B cell counts was manifested by the decrease of immature B cells , naïve B cells , resting memory B cells ,and plasmablasts .However ,tissue-like memory B cells increased significantly .ART could restore the frequencies of naïve B and tissue-like memory B cells ,but not the resting memory B cells .CD38 was significantly upregulated in immature B cells , naïve B cells , resting memory B cells and tissue-like memory B cells in HIV-1-infected patients ,when compared to healthy controls .All subpopulations showed higher expression of CD95 , and naïve B cells , tissue-like memory B cells and plasmablasts exhibited decreased levels of Bcl-2 . PD-1 was elevated only in resting memory cells and plasmablasts . The mean fluorescent intensity of CD40 was diminished in all B cell subpopulations ,whereas CD70 decreased in all subpopulations except immature B cells .However ,ART could only partially restore the altered expression of the mentioned molecules . These results suggest that HIV-1 infection leads to perturbation of B cell subpopulations ,and B cell subpopulations display hyperactivation ,susceptibility to apoptosis and impaired interaction with T cells .These alterations could only be restored partially by successful ART ,therefore , effective immune intervention strategies should be required .

  7. Combination antiretroviral therapy and the risk of myocardial infarction

    NARCIS (Netherlands)

    Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A

    2003-01-01

    Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collect

  8. Generic antiretroviral drugs and HIV care: An economic review.

    Science.gov (United States)

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures. PMID:26905394

  9. 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

  10. Cost analysis of antiretroviral agents available in India

    Directory of Open Access Journals (Sweden)

    Sagar S. Panchal

    2015-06-01

    Conclusion: There is wide variation in the prices of antiretroviral agents available in the market. Regulatory authorities, pharma companies, physicians should maximize their efforts to reduce the cost of drugs. [Int J Basic Clin Pharmacol 2015; 4(3.000: 479-482

  11. 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

  12. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

    Science.gov (United States)

    Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women

  13. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    2003-06-01

    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.

  14. 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

    OBJECTIVES: To derive and validate a clinically applicable prognostic score for predicting short-term disease progression in HIV-infected patients taking combination antiretroviral therapy (cART). DESIGN AND METHODS: Poisson regression was used to identify prognostic markers for new AIDS/death in......OBJECTIVES: To derive and validate a clinically applicable prognostic score for predicting short-term disease progression in HIV-infected patients taking combination antiretroviral therapy (cART). DESIGN AND METHODS: Poisson regression was used to identify prognostic markers for new AIDS....../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...

  15. Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

    Science.gov (United States)

    Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

    2016-01-01

    Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

  16. 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.

  17. 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

    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, ...... especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.......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, 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...

  18. 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.

  19. Eventos adversos relacionados à profilaxia anti-retroviral em acidentes ocupacionais Adverse events relating to antiretroviral prophylaxis for occupational accidents

    Directory of Open Access Journals (Sweden)

    Eduardo Alexandrino Servolo Medeiros

    2007-04-01

    Full Text Available O objetivo do estudo foi descrever os eventos adversos clínicos e laboratoriais secundários ao uso dos agentes anti-retrovirais em indivíduos submetidos à quimioprofilaxia. Foram avaliados 37 funcionários de um hospital universitário submetidos à quimioprofilaxia com quatro esquemas de medicação anti-retroviral após exposição ocupacional a fluidos de pacientes contaminados com infecção pelo vírus da imunodeficiência humana. Trinta e dois (86,5% desenvolveram eventos adversos clínicos ou laboratoriais. A profilaxia teve que ser suspensa em dois profissionais (5,4% em virtude das reações ocorridas. Os eventos adversos relacionados à quimioprofilaxia para infecção por HIV em funcionários de saúde, vítimas de acidente ocupacional foram freqüentes. Porém, raramente foi necessário retirar a medicação anti-retroviral.The objective of the study was to describe adverse events detected clinically or in the laboratory that were secondary to the use of antiretroviral agents among individuals undergoing antiretroviral prophylaxis. Evaluations were performed on 37 teaching hospital employees who underwent prophylaxis using four regimens of antiretroviral medication following occupational exposition to contaminated fluids from patients with human immunodeficiency virus infection. Thirty-two (86.5% developed adverse events detected clinically or in the laboratory. The prophylaxis administered to two professionals (5.4% had to be suspended because of the reactions that occurred. Adverse events relating to prophylaxis for HIV infection in health care workers who were victims of occupational accidents were frequent. However, it was rarely necessary to withdraw the antiretroviral medication.

  20. 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.

  1. The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

    OpenAIRE

    Josefsson, L.; von Stockenstrom, S.; Faria, N.R.; Sinclair, E; Bacchetti, P.; Killian, M.; Epling, L; Tan, A.; Ho, T; Lemey, P; W. Shao; Hunt, P. W.; SOMSOUK, M.; Wylie, W.; Douek, D C

    2013-01-01

    Identifying the source and dynamics of persistent HIV-1 during combinational antiretroviral therapy (cART) is crucial for understanding the barriers to curing HIV infection. Through genetic characterization of HIV-1 DNA in infected cells from peripheral blood and gut-associated lymphoid tissue from patients after long-term suppressive cART, our study reveals that the primary barrier to a cure is a remarkably stable pool of infected memory CD4+ T cells. Through in-depth phylogenetic analyses, ...

  2. Types of HIV/AIDS Antiretroviral Drugs

    Science.gov (United States)

    ... grouped by how they interfere with steps in HIV replication (PDF). Entry Inhibitors interfere with the virus' ability to bind to receptors on the outer surface of the cell it tries to enter. When receptor binding fails, HIV cannot infect the cell. Fusion Inhibitors interfere with ...

  3. Absolute Lymphocyte Count Is Not a Suitable Alternative to CD4 Count for Determining Initiation of Antiretroviral Therapy in Fiji

    Directory of Open Access Journals (Sweden)

    Dashika A. Balak

    2014-01-01

    Full Text Available Introduction. An absolute lymphocyte count is commonly used as an alternative to a CD4 count to determine initiation of antiretroviral therapy for HIV-infected individuals in Fiji when a CD4 count is unavailable. Methods. We conducted a retrospective analysis of laboratory results of HIV-infected individuals registered at all HIV clinics in Fiji. Results. Paired absolute lymphocyte and CD4 counts were available for 101 HIV-infected individuals, and 96% had a CD4 count of ≤500 cells/mm3. Correlation between the counts in individuals was poor (Spearman rank correlation r=0.5. No absolute lymphocyte count could be determined in this population as a suitable surrogate for a CD4 count of either 350 cells/mm3 or 500 cells/mm3. The currently used absolute lymphocyte count of ≤2300 cells/μL had a positive predictive value of 87% but a negative predictive value of only 17% for a CD4 of ≤350 cells/mm3 and if used as a surrogate for a CD4 of ≤500 cells/mm3 it would result in all HIV-infected individuals receiving ART including those not yet eligible. Weight, CD4 count, and absolute lymphocyte count increased significantly at 3 months following ART initiation. Conclusions. Our findings do not support the use of absolute lymphocyte count to determine antiretroviral therapy initiation in Fiji.

  4. Impact of immune reconstitution inflammatory syndrome on antiretroviral therapy adherence

    Directory of Open Access Journals (Sweden)

    Nachega JB

    2012-12-01

    Full Text Available Jean B Nachega,1,2,4 Chelsea Morroni,1 Richard E Chaisson,2–4 Rene Goliath,1 Anne Efron,4 Malathi Ram,2 Gary Maartens11University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa; 2Johns Hopkins University, Bloomberg School of Public Health, Departments of International Health and Epidemiology, 3Johns Hopkins University, School of Medicine, Department of Medicine, Division of Infectious Diseases, 4Johns Hopkins University, Center for Tuberculosis Research, Baltimore, Maryland, USAObjective: We determined the impact of immune reconstitution inflammatory syndrome (IRIS on antiretroviral therapy (ART adherence in a cohort of 274 human immunodeficiency virus (HIV-infected South African adults initiating ART.Methods: We carried out a secondary analysis of data from a randomized controlled trial of partially supervised ART in Cape Town, South Africa. Monthly pill count adherence, viral suppression (HIV viral load < 50 c/mL, and IRIS events were documented. Poisson regression was used to identify variables associated with ART adherence below the median in the first 6 months of ART.Results: We enrolled 274 patients: 58% women, median age 34 years, median CD4 count 98 cells/µL, 46% World Health Organization clinical stage IV, and 40% on treatment for tuberculosis (TB. IRIS and TB-IRIS developed in 8.4% and 6.6% of patients, respectively. The median cumulative adherence at 6 months for those with an IRIS event vs no IRIS was 95.5% vs 98.2% (P = 0.04. Although not statistically significant, patients developing IRIS had a lower 6-month viral load suppression than those without IRIS (68% vs 80%, P = 0.32. ART adherence below the median of 98% was independently associated with alcohol abuse (relative risk [RR] 1.5; 95% confidence interval [CI] 1.2–1.9; P = 0.003 and IRIS events (RR 1.7; 95% CI 1.2–2.2; P = 0.001.Conclusion: Although IRIS events were associated with slightly lower adherence rates, overall

  5. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults.

    Directory of Open Access Journals (Sweden)

    Emmanuel Maganga

    Full Text Available Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART, yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7% vs.11/153 (7.2%, p<0.001 and frank diabetes mellitus (27/150 (18.0% vs. 8/153 (5.2%, p = 0.001 than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78-11.77, p<0.001. Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.

  6. Discordant responses to cART in HIV-1 patients in the era of high potency antiretroviral drugs: clinical evaluation, classification, management prospects.

    Science.gov (United States)

    Cenderello, Giovanni; De Maria, Andrea

    2016-01-01

    The goal of antiretroviral treatment (ART) in HIV-1 patients is immune reconstitution following control of viral replication. CD4+ cell number/proportions are a crude but essential correlate of immune reconstitution. Despite suppression of HIV replication, a fraction of ART-treated patients still fails to fully reconstitute CD4+ T cell numbers (immunological nonresponders, INRs). New drugs, regimens and treatment strategies led to increased efficacy, lower side effects and higher virological success rates in clinical practice. The multitude of described immune defects and clinical events accompanying INR opposed to the marginal effect of antiretroviral intensification or immunotherapy trials underline the need for continuing efforts at understanding the mechanisms that underlie INR. Here, we reassess INR definition, frequency, and the achievements of active clinical and translational research suggesting a shared definition for insufficient, partial and complete CD4+ cell number recovery thus improving homogeneity in patient selection and mechanism identification. PMID:26513236

  7. Vibrational spectra and quantum mechanical calculations of antiretroviral drugs: Nevirapine

    Science.gov (United States)

    Ayala, A. P.; Siesler, H. W.; Wardell, S. M. S. V.; Boechat, N.; Dabbene, V.; Cuffini, S. L.

    2007-02-01

    Nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'e][1,4]diazepin-6-one) is an antiretroviral drug belonging to the class of the non-nucleoside inhibitors of the HIV-1 virus reverse transcriptase. As most of this kind of antiretroviral drugs, nevirapine displays a butterfly-like conformation which is preserved in complexes with the HIV-1 reverse transcriptase. In this work, we present a detailed vibrational spectroscopy investigation of nevirapine by using mid-infrared, near-infrared, and Raman spectroscopies. These data are supported by quantum mechanical calculations, which allow us to characterize completely the vibrational spectra of this compound. Based on these results, we discuss the correlation between the vibrational modes and the crystalline structure of the most stable form of nevirapine.

  8. Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Amon Joseph J

    2008-02-01

    Full Text Available Abstract Background Increasing access to antiretroviral therapy (ART is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed. Discussion Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drugs supply. International donors must help support and coordinate these efforts.

  9. Abnormal contingent negative variation in HIV patients receiving antiretroviral therapy

    OpenAIRE

    Chao, Linda L.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Rothlind, Johannes C.; Flenniken, Derek L.; Lindgren, Joselyn A.; Weiner, Michael W.

    2003-01-01

    The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virall...

  10. Antiretroviral Therapy and Demand for HIV Testing: Evidence from Zambia

    OpenAIRE

    Nicholas Wilson

    2010-01-01

    This paper examines the effects of antiretroviral therapy (ART) on demand for HIV testing and of ART-induced testing on demand for risky sexual behavior. I provide a model of sexual behavior decision-making under uncertainty and estimate the structural parameters of the model using nationally representative survey data from Zambia on HIV testing decisions before and after the introduction of ART. The empirical results indicate that although the introduction of ART increased demand for HIV tes...

  11. Barriers to Initiation of Antiretrovirals during Antituberculosis Therapy in Africa

    OpenAIRE

    Pepper, Dominique J.; Marais, Suzaan; Wilkinson, Robert J.; Bhaijee, Feriyl; De Azevedo, Virginia; Meintjes, Graeme

    2011-01-01

    Background 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. Method 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 (≥...

  12. The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties

    OpenAIRE

    Gatch, Michael B.; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C.; France, Charles P; Dillon, Glenn H.; Forster, Michael J.; Schetz, John A

    2013-01-01

    Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indola...

  13. Antiretrovirals to Prevent HIV Infection: Pre- and Postexposure Prophylaxis

    OpenAIRE

    Gay, Cynthia L.; Cohen, Myron S.

    2008-01-01

    More than 3 million people are now receiving antiretroviral therapy (ART) worldwide. Currently, the indications for ART depend primarily on CD4 count, blood viral burden, and clinical signs and symptoms suggesting advanced HIV disease. However, interest is increasing in ART’s preventive potential. Postexposure prophylaxis following both occupational and nonoccupational exposure to HIV is the standard-of-care in many settings. Observational and ecologic studies suggest that ART administered to...

  14. Preferred antiretroviral drugs for the next decade of scale up

    OpenAIRE

    Isabelle Andrieux-Meyer; Alexandra Calmy; Pedro Cahn; Polly Clayden; Gilles Raguin; Christine Katlama; Marco Vitoria; Andrew Levin; Sharonann Lynch; Eric Goemaere; Nathan Ford

    2012-01-01

    Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, unive...

  15. Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

    OpenAIRE

    Amon Joseph J

    2008-01-01

    Abstract Background Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been pr...

  16. African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy

    OpenAIRE

    Canter, Jeffrey A.; Robbins, Gregory K.; Selph, Doug; Clifford, David B.; Kallianpur, Asha R.; Shafer, Robert; Levy, Shawn; Murdock, Deborah G.; Ritchie, Marylyn D.; Haas, David W.; Hulgan, Todd

    2010-01-01

    Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) develope...

  17. Antiretroviral Therapy Adherence Among Transgender Women Living with HIV

    OpenAIRE

    Sevelius, Jae M.; Carrico, Adam; Johnson, Mallory O.

    2010-01-01

    Despite disproportionate rates of HIV among transgender women and evidence that medication adherence is necessary for treatment success and increased likelihood of survival, there has been little investigation into antiretroviral treatment (ART) adherence issues among transgender women. This study examined rates of self-reported ART adherence among transgender women on ART (n = 35) and well-established correlates of nonadherence including depression, adherence self-efficacy, patient perceptio...

  18. m-Health for antiretroviral treatment support : evidence from India

    OpenAIRE

    Rodrigues, Rashmi Josephine

    2014-01-01

    Background: With antiretroviral therapy (ART) HIV infection is now managed like a chronic disease rather than as a fatal disease. Adherence to ART is essential for treatment success. However the high levels of adherence that are necessary and the multifactorial nature of adherence, make adherence to ART a challenge. The recent years have seen a move towards the development of low cost interventions to support adherence to ART. The ...

  19. Antiretroviral Chemoprophylaxis: State of Evidence and the Research Agenda

    OpenAIRE

    Mayer, Kenneth H.

    2014-01-01

    Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP ...

  20. Predictive Utility of Brief AUDIT for HIV Antiretroviral Medication Nonadherence

    OpenAIRE

    Broyles, Lauren Matukaitis; Gordon, Adam J.; Sereika, Susan M.; Ryan, Christopher M.; Erlen, Judith A.

    2011-01-01

    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...

  1. Can Urine Lamivudine Be Used to Monitor Antiretroviral Treatment Adherence?

    Directory of Open Access Journals (Sweden)

    Kumar Agibothu

    2006-12-01

    Full Text Available Abstract Patient adherence to treatment is an important factor in the effectiveness of antiretroviral regimens. Adherence to treatment could be monitored by estimation of antiretroviral drugs in biological fluids. We aimed to obtain information on the quantity and duration of excretion of lamivudine in urine following oral administration of a single dose of 300 mg and to assess its suitability for adherence monitoring purposes. Spot urine samples were collected before dosing and at 4, 8, 12, 24, 28, 32, 48, 72, and 96 hours post dosing from 10 healthy subjects, and lamivudine was estimated by high-pressure liquid chromatography (HPLC. Lamivudine values were expressed as a ratio of urine creatinine. About 91% of the ingested drug was excreted by 24 hours, and the concentration thereafter in urine was very negligible. A lamivudine value of 0.035 mg/mg creatinine or less at 48 hours is suggestive of a missed dose in the last 24 hours. The study findings showed that estimation of urine lamivudine in spot specimens could be useful in monitoring patient adherence to antiretroviral treatment. However, this needs to be confirmed on a larger sample size and among patients on once-daily and twice-daily treatment regimens.

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

    OpenAIRE

    Gendelman, Howard

    2011-01-01

    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 Nebr...

  3. Directly Administered Antiretroviral Therapy: Pilot Study of a Structural Intervention in Methadone Maintenance

    OpenAIRE

    Sorensen, JL; Haug, NA; Larios, S; Gruber, VA; Tulsky, J; Powelson, E; Logan, DP; Shapiro, B.

    2012-01-01

    Devising interventions to provide integrated treatment for addiction and medical problems is an urgent issue. This study piloted a structural intervention, Directly Administered Antiretroviral Therapy (DAART), to assist methadone-maintenance patients in HIV medication adherence. Twenty-four participants received: (1) antiretroviral medications at the methadone clinic daily before receiving their methadone; (2) take-home antiretroviral medication for days they were not scheduled to attend the ...

  4. Antiretroviral therapy outcome in human immuno-deficiency virus infected patients in a tertiary care hospital

    OpenAIRE

    Hasitha Diana Manohar; Smita Shenoy; Muralidhar Varma; Asha Kamath; Chaithanya Malalur; Kurady Laxminarayana Bairy; Amod Tilak; Kavitha Saravu

    2016-01-01

    Background: Human immunodeficiency virus (HIV) presently accounts for the highest number of deaths due to any infective agent in the world. The present study assessed the one year treatment outcome following antiretroviral therapy in HIV positive, treatment na and iuml;ve patients in a tertiary care hospital. Methods: Adult HIV positive, antiretroviral treatment naive patients who were started on antiretroviral therapy (ART) between 1st January 2011 and 31st May 2013 were included in the s...

  5. The next generation of the World Health Organization's global antiretroviral guidance

    OpenAIRE

    Gottfried Hirnschall; Anthony D Harries; Easterbrook*, Philippa J.; Meg C Doherty; Andrew Ball

    2013-01-01

    The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and p...

  6. 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...

  7. French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults

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    Bruno Hoen

    2014-06-01

    Full Text Available Introduction: These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure. Methods: Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process. Results: ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine, or a ritonavir-boosted protease inhibitor (atazanavir or darunavir. Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression

  8. 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 en...... primary brain lymphoma. More advanced immunodeficiency is the dominant prognostic factor for mortality in patients with HIV-related NHL.......-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...

  9. 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 OBJECTIVE: The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART. METHODS: 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. RESULTS: 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. CONCLUSION: Discrete signs of systemic and vascular inflammation persist even after very long term cART.

  10. Free HIV Antiretroviral Therapy Enhances Adherence among Individuals on Stable Treatment: Implications for Potential Shortfalls in Free Antiretroviral Therapy

    OpenAIRE

    Byakika-Tusiime, Jayne; Polley, Eric C.; Oyugi, Jessica H.; Bangsberg, David R.

    2013-01-01

    Objective: To estimate the population-level causal effect of source of payment for HIV medication on treatment adherence using Marginal Structural Models. Methods: Data were obtained from an observational cohort of 76 HIV-infected individuals with at least 24 weeks of antiretroviral therapy treatment from 2002 to 2007 in Kampala, Uganda. Adherence was the primary outcome and it was measured using the 30-day visual analogue scale. Marginal structural models (MSM) were used to estimate the effe...

  11. Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study.

    Directory of Open Access Journals (Sweden)

    Jorge A Tavel

    Full Text Available BACKGROUND: The Study of Aldesleukin with and without antiretroviral therapy (STALWART evaluated whether intermittent interleukin-2 (IL-2 alone or with antiretroviral therapy (ART around IL-2 cycles increased CD4(+ counts compared to no therapy. METHODOLOGY: Participants not on continuous ART with > or = 300 CD4(+ cells/mm(3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4(+ counts, HIV RNA, and HIV progression events were collected monthly. PRINCIPAL FINDINGS: A total of 267 participants were randomized. At week 32, the mean CD4(+ count was 134 cells greater in the IL-2 alone group (p<0.001, and 133 cells greater in the IL-2 plus ART group (p<0.001 compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009. CONCLUSIONS: IL-2 alone or with peri-cycle HAART increases CD4(+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4(+ cells. TRIAL REGISTRATION: ClinicalTrials.gov NCT00110812.

  12. Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution

    Directory of Open Access Journals (Sweden)

    Simon David

    2010-12-01

    Full Text Available Abstract Background In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. Methods During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. Results Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years. All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5 versus controls (n = 73 were 44 vs.117 cells/mm3 (p = 0.09 and 5.2 vs. 4.2 log10 (p = 0.06, respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5 vs. 74 (n = 50(p = 0.284. Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5 vs. 1.94 (n = 50(p = 0.045. Conclusions An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors

  13. 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

  14. 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.

  15. Association between age at antiretroviral therapy initiation and 24-month immune response in West-African HIV-infected children

    DEFF Research Database (Denmark)

    Desmonde, Sophie; Dicko, Fatoumata; Koueta, Fla;

    2014-01-01

    OBJECTIVE: We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4 cell response in West African HIV-infected children. METHODS: All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4 cell count...... measurements, including one at ART initiation (baseline) were included. CD4 cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4 cell count, sex, first-line ART regimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model...... compared immune recovery for age within 24 months post-ART. RESULTS: Of the 4808 children initiated on ART, 3014 were enrolled at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4 cell gains compared with children less...

  16. Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment.

    Science.gov (United States)

    Rappaport, Jay; Volsky, David J

    2015-06-01

    Combination antiretroviral therapy (ART) has altered the outcomes of HIV infection in treated populations by greatly reducing the incidence of opportunistic infections, cancer, and HIV-associated dementia. Despite these benefits, treated patients remain at high risk of chronic diseases affecting the peripheral organs and brain. Generally, these morbidities are attributed to persistence of latent HIV in resting T cells, chronic inflammation, and metabolic effects of ART. This review makes the case that monocytes/macrophages warrant attention as persistent reservoirs of HIV under ART, source of systemic and brain inflammation, and important targets for HIV eradication to control chronic HIV diseases. PMID:25933548

  17. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice.

    OpenAIRE

    Horwitz, Joshua A.; Halper-Stromberg, Ariel; Mouquet, Hugo; Gitlin, Alexander D.; Tretiakova, Anna; Eisenreich, Thomas R.; Malbec, Marine; Gravemann, Sophia; Billerbeck, Eva; Dorner, Marcus; Büning, Hildegard; Schwartz, Olivier; Knops, Elena; Kaiser, Rolf; Seaman, Michael S

    2013-01-01

    Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1–infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, ...

  18. 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

  19. Recurrent Giant Molluscum Contagiosum Immune Reconstitution Inflammatory Syndrome (IRIS) after Initiation of Antiretroviral Therapy in an HIV-infected South African Male

    OpenAIRE

    Drain, Paul K.; Mosam, Anisa; Gounder, Lilishia; Gosnell, Bernadett; Manzini, Thandekile; Moosa, Mahomed-Yunus S.

    2013-01-01

    We describe an HIV-infected South African male who experienced two distinct episodes of disseminated giant molluscum contagiosum (MC) immune reconstitution inflammatory syndrome (IRIS) over a 6-year period. The first episode of MC-IRIS occurred with rapid virologic suppression following antiretroviral therapy (ART) initiation. The second episode occurred during a rapid increase in CD4 cells following stable viral suppression with second-line ART. His MC lesions then completely resolved during...

  20. Effect of nutritional factors on adherence to antiretroviral therapy among HIV-infected adults: a case control study in Northern Ethiopia

    OpenAIRE

    Berhe, Negassie; Tegabu, Desalegn; Alemayehu, Mekuriaw

    2013-01-01

    Background Adherence to antiretroviral treatment is critical for suppression of viral replication, reduced destruction of CD4 cells, prevention of viral resistance, promotion of immune reconstitution and slowed disease progression. This study sought to determine the effect of nutritional factors on adherence to ART among HIV-infected adults on ART. Methods Matched case control study design (matched by age and sex) was employed. Data was collected from ART registration chart, pre-tested struct...

  1. Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and research priorities for resource-limited settings

    NARCIS (Netherlands)

    Semvua, H.H.; Kibiki, G.S.; Kisanga, E.R.; Boeree, M.J.; Burger, D.M.; Aarnoutse, R.

    2015-01-01

    Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-

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

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; 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. Interruption of antiretroviral therapy is associated with increased plasma cystatin C

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Wyatt, Christina; Szczech, Lynda;

    2009-01-01

    continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. METHODS: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random...

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

    NARCIS (Netherlands)

    E. Martinez; F. Visnegarwala; B. Grund; A. Thomas; C. Gibert; J. Shlay; F. Drummond; D. Pearce; S. Edwards; P. Reiss; W. El-Sadr; A. Carr

    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 t

  5. 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; Gerstoft, Jan; Ostrowski, Sisse R

    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)....

  6. 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: Vi...

  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...

  8. Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy

    Science.gov (United States)

    Larson, Erica C.; Hathaway, Laura B.; Lamb, John G.; Pond, Chris D.; Rai, Prem P.; Matainaho, Teatulohi K.; Piskaut, Pius; Barrows, Louis R.; Franklin, Michael R.

    2014-01-01

    Ethnopharmacological relevance A substantial proportion of the population in Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment requires lifelong use of antiretroviral therapy (ART). The majority of people in PNG use traditional medicines (TM) derived from plants for all types of health promotions. Consequently, there is a concern that herb-drug interactions may impact the efficacy of ART. Herb-drug, or drug-drug, interactions occur at the level of metabolism through two major mechanisms: enzyme induction or enzyme inhibition. In this study, extracts of commonly-used medicinal plants from PNG were screened for herb-drug interactions related to cytochrome P450s (CYPs). Materials and Methods Sixty nine methanol extracts of TM plants were screened for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially available cell-based luciferase reporter system. Inhibition of three major CYPs, CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and enzyme-selective model substrates. Results Almost one third of the TM plant extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and inhibition properties. Conclusions We demonstrated that the potent and selective ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes through induction and/or inhibition is a common phenomenon. Use of traditional medicines concomitantly with ART could dramatically alter the concentrations of antiretroviral drugs in the body; and their efficacy. PNG healthcare providers should counsel HIV patients because of this consequence. PMID:25138353

  9. Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    van der Merwe Karin

    2011-08-01

    Full Text Available Abstract Background Use of highly active antiretroviral therapy (HAART, a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development. Methods Our objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight ( Results Among HAART-unexposed infants, 27% (60/224 were low birth weight compared with 23% (90/388 of early HAART-exposed (exposed 3 increase, 95% CI 0.45-0.71, p 3 increase, 95% CI 0.55-0.85, p = 0.001. HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001, with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p Conclusions In this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.

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

    Directory of Open Access Journals (Sweden)

    Regina Flávia de Castro Almeida

    2009-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Jorge L Salinas

    Full Text Available OBJECTIVES: 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. DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

  12. HIV-1 antiretrovirals induce oxidant injury and increase intima-media thickness in an atherogenic mouse model

    OpenAIRE

    Jiang, Bo; Hebert, Valeria Y.; Khandelwal, Alok R.; Stokes, Karen Y.; Dugas, Tammy R

    2009-01-01

    A growing body of evidence suggests HIV patients are at a greater risk for developing atherosclerosis. However, clinical investigations have generated conflicting results with regard to whether antiretrovirals are independently involved in the development of HIV-associated atherosclerosis. By administering antiretrovirals in an atherogenic mouse model, we determined whether two commonly prescribed antiretrovirals, the protease inhibitor indinavir and the nucleoside reverse transcriptase inhib...

  13. Delayed HIV diagnosis and initiation of antiretroviral therapy

    DEFF Research Database (Denmark)

    Lodi, Sara; Dray-Spira, Rosemary; Touloumi, Giota;

    2014-01-01

    nine HIV cohorts within COHERE in Austria, France, Greece, Italy, Spain and Switzerland, collecting data on level of education in categories of the UNESCO/International Standard Classification of Education standard classification: non-completed basic, basic, secondary and tertiary education. We......OBJECTIVES: In Europe and elsewhere, health inequalities among HIV-positive individuals are of concern. We investigated late HIV diagnosis and late initiation of combination antiretroviral therapy (cART) by educational level, a proxy of socioeconomic position. DESIGN AND METHODS: We used data from...

  14. Antiretroviral Therapy for Prevention of Human Immunodeficiency Virus Infection.

    Science.gov (United States)

    Kalapila, Aley G; Marrazzo, Jeanne

    2016-07-01

    Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622

  15. Combination antiretroviral studies for patients with primary biliary cirrhosis.

    Science.gov (United States)

    Lytvyak, Ellina; Montano-Loza, Aldo J; Mason, Andrew L

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label

  16. 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...... 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...

  17. Maternal deaths following nevirapine-based antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    E Bera

    2012-11-01

    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.

  18. Overview of antiretroviral treatment in China: advancement and challenges

    Institute of Scientific and Technical Information of China (English)

    LUO Ling; LI Tai-sheng

    2011-01-01

    As the severity of the HIV epidemic in China grew, National Free Antiretroviral Treatment (ART) Program was announced since 2003. Even though there still were many difficulties, China had obtained great achievements in fighting against HIV.Over 52 000 adult patients had received first-line HAART thus far and the mortality of AIDS in China decreased significantly. This paper presents an overview of the HIV/AIDS epidemic in China; the status of national free ART program,the difficulties suffered and the achievements made since the initiation of program and the challenges ahead for continued progress for China. This paper also provides suggestions to overcome these challenges.

  19. Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

    OpenAIRE

    Rupak Shivakoti; Nikhil Gupte; Wei-Teng Yang; Noluthando Mwelase; Cecilia Kanyama; Tang, Alice M.; Sandy Pillay; Wadzanai Samaneka; Cynthia Riviere; Sima Berendes; Lama, Javier R.; Cardoso, Sandra W.; Patcharaphan Sugandhavesa; Richard D Semba; Parul Christian

    2014-01-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic...

  20. World Health Organization guidelines should not change the CD4 count threshold for antiretroviral therapy initiation

    Directory of Open Access Journals (Sweden)

    Nathan Geffen

    2013-03-01

    Full Text Available The World Health Organization (WHO currently recommends that HIV-positive adults start antiretroviral therapy (ART at CD4 counts <350 cells/μl. Several countries have changed their guidelines to recommend ART irrespective of CD4 count or at a threshold of 500 CD4 cells/μl. Consequently, WHO is currently revising its treatment guidelines and considering recommending ART initiation at CD4 counts <500 cells/μl. Such decisions are critically important, as WHO guidelines inform healthcare policies in developing countries and are used by activists in their advocacy work. Changing the CD4 initiation point from 350 to 500 cells/μl would, however, be premature and have profound cost implications on Global Fund, President’s Emergency Plan for AIDS Relief (PEPFAR and developing country health budgets. We should be willing to campaign for such a change in guidelines despite cost implications, if supported by evidence. However, the evidence remains outstanding. S Afr J HIV Med 2013;14(1:6-7. DOI:10.7196/SAJHIVMED.906

  1. Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS

    Directory of Open Access Journals (Sweden)

    Lorna A Renner

    2013-09-01

    Full Text Available Introduction: There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART containing zidovudine (ZDV recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods: Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥18 months followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results: As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was−2.7; and 1772 (60.4% had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p≤0.01: the prevalence of severe anaemia was 3.0% (n=38 in the ZDV group versus 10.2% (n=89 in those without (p<0. 01. Over the first-line follow-up, 58.9% of the children had ≥1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45. Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p≤0.01. Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤−3 was a strong predictor associated with a 5.59 times risk of

  2. Safety and effectiveness of combination antiretroviral therapy during the first year of treatment in HIV-1 infected Rwandan children: a prospective study.

    Directory of Open Access Journals (Sweden)

    Philippe R Mutwa

    Full Text Available With increased availability of paediatric combination antiretroviral therapy (cART in resource limited settings, cART outcomes and factors associated with outcomes should be assessed.HIV-infected children -2, immunological success as CD4 cells ≥500/mm3 and ≥25% for respectively children over 5 years and under 5 years, and virological success as a plasma HIV-1 RNA concentration 1000 c/mL. Older age at cART initiation, poor adherence, and exposure to antiretrovirals around birth were associated with virological failure. A third (33% of children had side effects (by self-report or clinical assessment, but only 9% experienced a severe side effect requiring a cART regimen change.cART in Rwandan HIV-infected children was successful but success might be improved further by initiating cART as early as possible, optimizing adherence and optimizing management of side effects.

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

    Directory of Open Access Journals (Sweden)

    Manisha V Ghate

    2014-01-01

    Full Text Available 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 naοve 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 naοve 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/mm 3 (P < 0.01 and illiteracy (P = 0.044 were significantly associated with LFU. Of the total pre-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.

  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. Antiretroviral chemoprophylaxis: state of evidence and the research agenda.

    Science.gov (United States)

    Mayer, Kenneth H

    2014-07-01

    Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP protection appears to be highly correlated with medication adherence. New studies are evaluating whether different antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors. Different formulations are also being evaluated, including gels, films, vaginal rings, and injectable medication. Although PrEP efficacy has been demonstrated, and several normative bodies (eg, the US Food and Drug Administration) have approved PrEP for clinical use, uptake has been slow. Reasons may include lack of sufficient provider and consumer education, residual concerns about costs, potential long-term toxicities, and behavioral disinhibition. Additional work is under way to determine how to best educate consumers and providers about optimal adherence and to use PrEP in conjunction with risk mitigation. PMID:24926034

  6. Predictive Models for Maximum Recommended Therapeutic Dose of Antiretroviral Drugs

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    Michael Lee Branham

    2012-01-01

    Full Text Available A novel method for predicting maximum recommended therapeutic dose (MRTD is presented using quantitative structure property relationships (QSPRs and artificial neural networks (ANNs. MRTD data of 31 structurally diverse Antiretroviral drugs (ARVs were collected from FDA MRTD Database or package inserts. Molecular property descriptors of each compound, that is, molecular mass, aqueous solubility, lipophilicity, biotransformation half life, oxidation half life, and biodegradation probability were calculated from their SMILES codes. A training set (=23 was used to construct multiple linear regression and back propagation neural network models. The models were validated using an external test set (=8 which demonstrated that MRTD values may be predicted with reasonable accuracy. Model predictability was described by root mean squared errors (RMSEs, Kendall's correlation coefficients (tau, P-values, and Bland Altman plots for method comparisons. MRTD was predicted by a 6-3-1 neural network model (RMSE=13.67, tau=0.643, =0.035 more accurately than by the multiple linear regression (RMSE=27.27, tau=0.714, =0.019 model. Both models illustrated a moderate correlation between aqueous solubility of antiretroviral drugs and maximum therapeutic dose. MRTD prediction may assist in the design of safer, more effective treatments for HIV infection.

  7. Cost-effectiveness analysis of antiretroviral therapy in a cohort of HIV-infected patients starting first-line highly active antiretroviral therapy during 6 years of observation

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    Maggiolo F

    2015-02-01

    Full Text Available Franco Maggiolo,1 Giorgio L Colombo,2,3 Sergio Di Matteo,3 Giacomo M Bruno,3 Noemi Astuti,1 Elisa Di Filippo,1 Giulia Masini,1 Claudia Bernardini1 1Division of Infectious Diseases, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; 2University of Pavia, Department of Drug Sciences, Pavia, Italy; 3SAVE Studi Analisi Valutazioni Economiche, Milan, Italy Objectives: Costs may play a role in deciding how and when to start highly active antiretroviral therapy (HAART in a naïve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naïve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV. An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach. Results: In total, 741 patients (females comprising 25.5% were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/µL, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%; zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/µL and CD4 351–500 cells/µL rather than at <201 cells/µL was the more cost-effective approach. The same consideration was not true comparing current indications with the possibility to start HAART at any CD4 value (eg, >500 cells per µL; in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR invariably

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

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    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.

  9. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

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    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A.; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A.; Nekhai, Sergei; Akala, Emmanuel O.

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  10. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment.

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    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A; Nekhai, Sergei; Akala, Emmanuel O

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  11. 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.

  12. HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood

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    Niculescu, Irina; Cupşa, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

    2013-01-01

    Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-naïve horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.288±4.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.742±5.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33±148.10 cells/ml, non-CoS-163.17±155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.06±0.80 lgcopies/ml (for 29 subjects), non-CoS-5.04±0.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068±141.676 cells/ml, non-CoS-176.015±191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.04±0.79 lgcopies/ml, non-COS-4.69±2.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

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

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    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 Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p 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. PMID:26544766

  14. Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda

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    Namagala Elizabeth

    2009-08-01

    Full Text Available Abstract Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%, 24 of 40 clinical officers (60%, 16 of 114 nurses (14% and 13 of 54 midwives (24% who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p Conclusion Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.

  15. Direct-to-consumer advertisements for HIV antiretroviral medications: a progress report.

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    Kallen, Alexander; Woloshin, Steven; Shu, Jennifer; Juhl, Ellen; Schwartz, Lisa

    2007-01-01

    Direct-to-consumer (DTC) prescription drug advertisements for HIV anti-retrovirals are controversial and have been criticized in the past for including deceptive images and underplaying HIV drug limitations. We sought to describe the state of recent DTC ads for HIV antiretrovirals in popular magazines by performing a content analysis of all complete DTC ads for antiretroviral medications appearing in eight national magazines during a one-year period. Current ads appear to have addressed previous concerns, but important problems still exist, such as failing to specify the medication's role in current treatment, to quantify drug efficacy, or to highlight life-threatening side effects. PMID:17848450

  16. Antiretroviral activity of 5-azacytidine during treatment of a HTLV-1 positive myelodysplastic syndrome with autoimmune manifestations

    Science.gov (United States)

    2012-01-01

    Myelodysplastic syndromes (MDS) are often accompanied by autoimmune phenomena. The underlying mechanisms for these associations remain uncertain, although T cell activation seems to be important. Human T-lymphotropic virus (HTLV-1) has been detected in patients with myelodysplastic syndromes, mostly in regions of the world which are endemic for the virus, and where association of HTLV-1 with rheumatological manifestation is not rare. We present here the case of a 58 year old man who presented with cytopenias, leukocytoclastic vasculitis of the skin and glomerulopathy, and was diagnosed as MDS (refractory anemia with excess blasts - RAEB 1). The patient also tested positive for HTLV-1 by PCR. After 8 monthly cycles of 5-azacytidine he achieved a complete hematologic remission. Following treatment, a second PCR for HTLV-1 was carried out and found to be negative. This is the first report in the literature of a HTLV-1-positive MDS with severe autoimmune manifestations, which was treated with the hypomethylating factor 5-azacitidine, achieving cytogenetic remission with concomitant resolution of the autoimmune manifestations, as well as HTLV-1-PCR negativity. HTLV-1-PCR negativity may be due to either immune mediated clearance of the virus, or a potential antiretroviral effect of 5-azacytidine. 5-azacytidine is known for its antiretroviral effects, although there is no proof of its activity against HTLV-1 infection in vivo. PMID:22214262

  17. Antiretroviral activity of 5-azacytidine during treatment of a HTLV-1 positive myelodysplastic syndrome with autoimmune manifestations

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    Diamantopoulos Panagiotis T

    2012-01-01

    Full Text Available Abstract Myelodysplastic syndromes (MDS are often accompanied by autoimmune phenomena. The underlying mechanisms for these associations remain uncertain, although T cell activation seems to be important. Human T-lymphotropic virus (HTLV-1 has been detected in patients with myelodysplastic syndromes, mostly in regions of the world which are endemic for the virus, and where association of HTLV-1 with rheumatological manifestation is not rare. We present here the case of a 58 year old man who presented with cytopenias, leukocytoclastic vasculitis of the skin and glomerulopathy, and was diagnosed as MDS (refractory anemia with excess blasts - RAEB 1. The patient also tested positive for HTLV-1 by PCR. After 8 monthly cycles of 5-azacytidine he achieved a complete hematologic remission. Following treatment, a second PCR for HTLV-1 was carried out and found to be negative. This is the first report in the literature of a HTLV-1-positive MDS with severe autoimmune manifestations, which was treated with the hypomethylating factor 5-azacitidine, achieving cytogenetic remission with concomitant resolution of the autoimmune manifestations, as well as HTLV-1-PCR negativity. HTLV-1-PCR negativity may be due to either immune mediated clearance of the virus, or a potential antiretroviral effect of 5-azacytidine. 5-azacytidine is known for its antiretroviral effects, although there is no proof of its activity against HTLV-1 infection in vivo.

  18. Computed CD4 percentage as a low-cost method for determining pediatric antiretroviral treatment eligibility

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    Colebunders Robert

    2008-03-01

    Full Text Available Abstract Background The performance of the WHO recommendations for pediatric antiretroviral treatment (ART in resource poor settings is insufficiently documented in routine care. Methods We compared clinical and immunological criteria in 366 children aged 0 to 12 years in Kinshasa and evaluated a simple computation to estimate CD4 percent, based on CD4 count, total white blood cell count and percentage lymphocytes. Kappa (κ statistic was used to evaluate eligibility criteria and linear regression to determine trends of CD4 percent, count and total lymphocyte count (TLC. Results Agreement between clinical and immunological eligibility criteria was poor (κ = 0.26. One third of children clinically eligible for ART were ineligible using immunological criteria; one third of children immunologically eligible were ineligible using clinical criteria. Among children presenting in WHO stage I or II, 54 (32% were eligible according to immunological criteria. Agreement with CD4 percent was poor for TLC (κ = 0.04, fair for total CD4 count (κ = 0.39 and substantial for CD4 percent computational estimate (κ = 0.71. Among 5 to 12 years old children, total CD4 count was higher in younger age groups (-32 cells/mm3 per year older, CD4 percent was similar across age groups. Conclusion Age-specific thresholds for CD4 percent optimally determine pediatric ART eligibility. The use of CD4 percent computational estimate may increase ART access in settings with limited access to CD4 percent assays.

  19. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

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    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

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

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    Marlene Knight

    2015-04-01

    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.

  1. Risk factors for intestinal parasitosis among antiretroviral-treated HIV/AIDS patients in Ethiopia.

    Science.gov (United States)

    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. PMID:24554001

  2. Albuminuria is associated with elevated acute phase reactants and proinflammatory markers in HIV-infected patients receiving suppressive combination antiretroviral therapy.

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    O-charoen, Pichaya; Ndhlovu, Lishomwa C; Gangcuangco, Louie Mar A; Keating, Sheila M; Norris, Philip J; Ng, Roland C K; Mitchell, Brooks I; Shikuma, Cecilia M; Chow, Dominic C

    2014-12-01

    Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with HIV-Cardiovascular Cohort. Plasma inflammatory biomarkers were assessed using the Milliplex Human Cardiovascular disease multiplex assays. A random urine sample was collected for albumin measurement. Albuminuria was defined as urine albumin-to-creatinine ratio of ≥30 mg/g. Framingham risk score was calculated and divided into three classes. Simple and multivariable logistic regression analyses were utilized to assess the correlation between plasma inflammatory biomarkers and albuminuria and were adjusted for Framingham risk category. Among 111 HIV-infected patients [median (IQR) age of 52 (46-57) years, 86% male, median (IQR) CD4 count of 489 (341-638) cells/mm(3), 85% with HIV RNA CVD risk factors. This study showed an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects who were on combination antiretroviral therapy (cART). Chronic inflammation despite potent antiretroviral treatment may contribute to higher rates of albuminuria among HIV-infected patients. PMID:25205472

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

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    Anand Moodley

    2014-05-01

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

  4. Antiretroviral therapy and demand for HIV testing: Evidence from Zambia.

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    Wilson, Nicholas

    2016-05-01

    This paper examines the effects of antiretroviral therapy (ART) on demand for HIV testing and of ART-induced testing on demand for risky sexual behavior. I provide a model of sexual behavior decision-making under uncertainty and estimate the structural parameters of the model using nationally representative survey data from Zambia on HIV testing decisions before and after the introduction of ART. The empirical results indicate that although the introduction of ART appears to have increased HIV testing rates by upwards of 50 percent, the ART allocation process may have limited the prevention benefit of ART-induced testing. Simulation results show that eliminating this prevention inefficiency while holding the supply of ART constant would increase the prevention impact of ART-induced testing more than four-fold. More generally, the analysis indicates that existing studies which examine "universal" testing or quasi-experimental testing programs understate the efficacy of standard voluntary counseling and testing programs. PMID:26970992

  5. Safety profile of antiretroviral therapy: An urgent need for monitoring

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    Dhaka Ram Bhandari

    2016-01-01

    Full Text Available The diminution of CD4 lymphocytes is the diagnostic characteristic of human immunodeficiency virus (HIV infection. Since the discovery of the disease 35 years ago, the infection has become one of the greatest menaces for the modern civilization. There are many individual drug toxicities and a number of class-specific or therapy-related toxicities of anti-HIV agents. Hepatotoxicity is a well-recognized side effect developing asymptomatic mild elevation of transaminases. It is known that the incidence of adverse reactions is high in long-term reactions such as lipodystrophy, paresthesia, and neuromotor disorders. Antiretroviral (ARV therapy is not only effective but also complex. There are many adverse effects of the therapy, which affect varieties of the organ system. To optimize the treatment, health professionals should focus on preventing the adverse effect of ARV agents.

  6. Preferred antiretroviral drugs for the next decade of scale up

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    Isabelle Andrieux-Meyer

    2012-09-01

    Full Text Available Global commitments aim to provide antiretroviral therapy (ART to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.

  7. Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.

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    Luni, Faraz Khan; Khan, Abdur Rahman; Prashar, Rohini; Vetteth, Sandeep; Duggan, Joan M

    2016-01-01

    Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure. PMID:24914503

  8. Highly active antiretroviral therapy: Does it Sound toxic?

    Directory of Open Access Journals (Sweden)

    Katijah Khoza-Shangase

    2011-01-01

    Full Text Available Objective : The main objective of the current study is to monitor the auditory status in a group of adults with AIDS, receiving Highly Active Antiretroviral Therapy (HAART (3TC -lamivudine, D4T - stavudine, and efavirenz in a hospital outpatient clinic in Gauteng. A total sample of 54 adults (between the ages of 18 and 50 years in the experimental group and 16 in the control group were assessed prospectively following a repeated measures design. All participants were assessed at baseline at three months, and at six months into the treatment. Materials and Methods : The participants underwent case history interviews and medical record reviews, otoscopy, and tympanometry, as well as conventional pure tone audiometry and distortion product otoacoustic emission testing. Both descriptive and inferential statistics were used to analyze the data. Results : On audiological monitoring, statistically significant changes (P<0.05 were established, only in the experimental group, for pure tone audiometry - with clinically significant changes found at high frequencies. Statistically significant changes with clinically significant changes were obtained for distortion product otoacoustic emissions (DPOAEs in the experimental group, particularly at high frequencies - implying subclinical hearing function changes; while lack of statistically significant changes with no clinically significant changes were found in the control group. The subclinical hearing changes in the experimental group were also evident in the findings of the subclinical hearing loss group, who, although they had normal pure tone function after six months of follow up, presented with clinical changes on DPOAEs at 6 and 8 kHz. Conclusions : Findings highlight the need for closer monitoring of the effects of antiretroviral drugs (ARVs on hearing, through the use of more sensitive tools of assessment when conducting drug trials.

  9. 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

  10. Use of third line antiretroviral therapy in Latin America.

    Directory of Open Access Journals (Sweden)

    Carina Cesar

    Full Text Available 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.

  11. Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique

    Directory of Open Access Journals (Sweden)

    Decroo Tom

    2009-05-01

    Full Text Available Abstract As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care. In Tete City, Mozambique, patients on antiretrovirals were rapidly down referred from a provincial hospital to four urban clinics in large numbers without careful planning, resulting in a number of patients being lost to follow-up. We outline some key lessons learned to support down referral, including the need to improve process management, clinic infrastructure, monitoring systems, and patient preparation. Down referral can be avoided by initiating patients' antiretroviral treatment at clinic level from the outset.

  12. HIV Infection and Risk for Incident Pulmonary Diseases in the Combination Antiretroviral Therapy Era

    OpenAIRE

    Crothers, Kristina; Huang, Laurence; Goulet, Joseph L.; Goetz, Matthew Bidwell; Brown, Sheldon T.; Rodriguez-Barradas, Maria C.; Oursler, Krisann K.; Rimland, David; Gibert, Cynthia L.; Butt, Adeel A.; Justice, Amy C.

    2011-01-01

    Rationale: In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era.

  13. The charms and challenges of antiretroviral therapy in Uganda: the DART experience.

    OpenAIRE

    Nyanzi-Wakholi, B; Lara, AM; Munderi, P.; Gilks, C.; Dart Trial Team, (incl. Grosskurth, H. )

    2012-01-01

    : Antiretroviral therapy (ART) improves the quality of life of people living with HIV/AIDS. However, adherence remains a challenge. A total of eight focus group discussions (FGD) were conducted with participants from a randomised controlled trial that monitored strategies for managing ART in African adults: Development of Antiretroviral Therapy. All FGD participants had received ART for at least one year. Perceived benefits of ART were key motivators for adherence. These benefits included imp...

  14. Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.

    Science.gov (United States)

    Bottonari, Kathryn A; Tripathi, Shanti P; Fortney, John C; Curran, Geoff; Rimland, David; Rodriguez-Barradas, Maria; Gifford, Allen L; Pyne, Jeffrey M

    2012-05-01

    Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n=146), an antiretroviral (n=192), or both (n=113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence" or "90% or greater adherence." After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n=146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n=112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n=113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (β=1.62, p=0.17), however, antidepressant adherence

  15. 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....

  16. Patterns of Geographic Mobility Predict Barriers to Engagement in HIV Care and Antiretroviral Treatment Adherence

    OpenAIRE

    Taylor, Barbara S.; Reyes, Emily; Levine, Elizabeth A.; Khan, Shah Z.; Garduño, L. Sergio; Donastorg, Yeycy; Hammer, Scott M.; Brudney, Karen; Hirsch, Jennifer S.

    2014-01-01

    Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6...

  17. 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.

  18. Pharmacogenetics of antiretroviral drugs for the treatment of HIV-infected patients : An update

    OpenAIRE

    Cressey, Tim R.; Lallemant, Marc

    2007-01-01

    Highly active antiretroviral therapy (HAART), a combination of at least three antiretroviral drugs, has dramatically improved the prognosis of HIV/AIDS. However, viral replication under therapy can lead to the selection of drug resistant viruses and subsequent virologic failure. While poor adherence is likely to be the main cause of treatment failure, individual pharmacokinetic variability can also play an important role. Drug-drug interactions, drug-food interactions, sex, age, renal/hepatic...

  19. Virologic, immunologic and clinical response of infants to antiretroviral therapy in Kampala, Uganda

    OpenAIRE

    Tukei, Vincent J; Murungi, Miriam; Asiimwe, Alice R; Migisha, Daniella; Maganda, Albert; Bakeera-Kitaka, Sabrina; Kalyesubula, Israel; Musoke, Philippa; Kekitiinwa, Adeodata

    2013-01-01

    Background Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda. Methods A prospective cohort of HIV-infected infants receiving treatment at the Baylor-Uga...

  20. The effect of socio-economic status on adherence to Anti-retroviral therapy

    OpenAIRE

    Akindele, Rasaq Akintunde; Fasanu, Adeniyi Olanipekun; Mabayoje, Victor Olatunji; Adisa, Patricia Olukorede; Adeniran Samuel ATIBA; Babatunde, Samuel Olusegun

    2015-01-01

    Background: Human Immunodeficiency Virus infection is a pandemic disease threatening public health for decades now. With the advent of antiretroviral drugs (ARDs) being taken on long term basis, it is important to examine factors that could affect adherence to these medicationsObjectives: To determine relationship between socio-economic status of sero-positive HIV patients on antiretroviral drugs and their adherence to these drugsMethods:  This is a descriptive cross sectional study. One hund...

  1. Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

    OpenAIRE

    Cohen, Myron S.; Smith, M. Kumi; Muessig, Kathryn E.; Hallett, Timothy B.; Powers, Kimberly A.; Kashuba, Angela D.

    2013-01-01

    Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier in...

  2. Sources of motivation and frustration among healthcare workers administering antiretroviral treatment for HIV in rural Zimbabwe

    OpenAIRE

    Campbell, Catherine M.; Scott, Kerry; Madenhire, C.; Nyamukapa, Constance; Gregson, Simon

    2011-01-01

    The roll-out of accessible and affordable antiretroviral (ARV) drugs for people living with HIV in low-income countries is drastically changing the nature of HIV-related healthcare. The Zimbabwean Ministry of Health has renewed efforts to make antiretroviral treatment (ART) for HIV free and publically available across the country. This paper describes the findings from a multi-method qualitative study including interviews and a focus group with healthcare workers (mostly nurses), totalling 25...

  3. The Complexity of HIV Persistence and Pathogenesis in the Lung Under Antiretroviral Therapy: Challenges Beyond AIDS

    OpenAIRE

    Almodovar, Sharilyn

    2014-01-01

    Antiretroviral therapy (ART) represents a significant milestone in the battle against AIDS. However, we continue learning about HIV and confronting challenges 30 years after its discovery. HIV has cleverly tricked both the host immune system and ART. First, the many HIV subtypes and recombinant forms have different susceptibilities to antiretroviral drugs, which may represent an issue in countries where ART is just being introduced. Second, even under the suppressive pressures of ART, HIV sti...

  4. 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...

  5. A Patient with Multiple Immune Reconstitution Inflammatory Syndrome (IRIS) Following Initiation of Antiretroviral Therapy

    OpenAIRE

    Achappa, Basavaprabhu; Madi, Deepak; Shetty, Nishitha; Mahalingam, Soundarya

    2012-01-01

    The Immune Reconstitution Inflammatory Syndrome (IRIS) is an exaggerated pathological inflammatory reaction which occurs after the initiation of the antiretroviral therapy, due to the exuberant immune responses to the occult or the apparent opportunistic infections. The hallmark of the syndrome is the paradoxical worsening of an existing infection or a disease process or the appearance of a new infection or a disease process soon after the initiation of the antiretroviral therapy.

  6. Technology-Based Self-Care Methods of Improving Antiretroviral Adherence: A Systematic Review

    OpenAIRE

    SABERI, Parya; Johnson, Mallory O.

    2011-01-01

    Background 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. Methodology/Principal Findings Technology-based methods are increasingly used to enhance antiretroviral adherence; therefore, we system...

  7. Quality of life of people living with HIV and AIDS and antiretroviral therapy

    OpenAIRE

    Oguntibeju OO

    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...

  8. Factors Influencing Adherence to Antiretroviral Treatment in Nepal: A Mixed-Methods Study

    OpenAIRE

    Wasti, Sharada P.; Simkhada, Padam; Randall, Julian; Freeman, Jennifer V; van Teijlingen, Edwin

    2012-01-01

    Background Antiretroviral therapy (ART) is a lifesaver for individual patients treated for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). Maintaining optimal adherence to antiretroviral drugs is essential for HIV infection management. This study aimed to understand the factors influencing adherence amongst ART-prescribed patients and care providers in Nepal. Methods A cross-sectional mixed-methods study surveying 330 ART-prescribed patients and 34 in-depth ...

  9. Self-reported adverse reactions among patients initiating antiretroviral therapy in Brazil

    OpenAIRE

    Cristiane A. Menezes de Pádua; Cibele C. César; Palmira F. Bonolo; Francisco A. Acurcio; Mark Drew C. Guimarães

    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...

  10. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

    OpenAIRE

    Anglemyer, Andrew; Rutherford, George W.; Horvath, Tara; Baggaley, Rachel C; Egger, Matthias; Siegfried, Nandi

    2013-01-01

    BACKGROUND Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). OBJECTIVES To determine if ART use in an HIV-infected member of an HIV-discordant couple is ...

  11. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

    OpenAIRE

    2003-01-01

    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...

  12. Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients.

    Science.gov (United States)

    Calza, Leonardo; Colangeli, Vincenzo; Manfredi, Roberto; Bon, Isabella; Re, Maria Carla; Viale, Pierluigi

    2016-06-01

    The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents. PMID:26846208

  13. Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and research priorities for resource-limited settings.

    Science.gov (United States)

    Semvua, Hadija H; Kibiki, Gibson S; Kisanga, Elton R; Boeree, Martin J; Burger, David M; Aarnoutse, Rob

    2015-02-01

    Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need. PMID:24943062

  14. Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy.

    Science.gov (United States)

    Sede, Mariano; Parra, Micaela; Manrique, Julieta M; Laufer, Natalia; Jones, Leandro R; Quarleri, Jorge

    2016-09-01

    Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses. PMID:27234841

  15. Transient antiretroviral therapy selecting for common HIV-1 mutations substantially accelerates the appearance of rare mutations

    Directory of Open Access Journals (Sweden)

    Shiri Tinevimbo

    2008-11-01

    Full Text Available Abstract Background Highly selective antiretroviral (ARV regimens such as single dose nevirapine (NVP used for prevention of mother to child transmission (PMTCT in resource-limited settings produce transient increases in otherwise marginal subpopulations of cells infected by mutant genomes. The longer term implications for accumulation of further resistance mutations are not fully understood. Methods We develop a new strain-differentiated hybrid deterministic-stochastic population dynamic type model of healthy and infected cells. We explore how the transient increase in a population of cells transcribed with a common mutation (modelled deterministically, which occurs in response to a short course of monotherapy, has an impact on the risk of appearance of rarer, higher-order, therapy-defeating mutations (modelled stochastically. Results Scenarios with a transient of a magnitude and duration such as is known to occur under NVP monotherapy exhibit significantly accelerated viral evolution compared to no-treatment scenarios. We identify a possibly important new biological timescale; namely, the duration of persistence, after a seminal mutation, of a sub-population of cells bearing the new mutant gene, and we show how increased persistence leads to an increased probability that a rare mutant will be present at the moment at which a new treatment regimen is initiated. Conclusion Even transient increases in subpopulations of common mutants are associated with accelerated appearance of further rarer mutations. Experimental data on the persistence of small subpopulations of rare mutants, in unfavourable environments, should be sought, as this affects the risk of subverting later regimens.

  16. Rinossinusites em crianças infectadas pelo HIV sob terapia anti-retroviral Rhinosinusitis in HIV-infected children undergoing antiretroviral therapy

    OpenAIRE

    Carlos Diógenes Pinheiro Neto; Raimar Weber; Bernardo Cunha Araújo-Filho; Ivan Dieb Miziara

    2009-01-01

    A associação dos inibidores de protease (IP) à terapia anti-retroviral provocou mudanças importantes na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto desta associação na prevalência de rinossinusite (RS) e na contagem sérica de linfócitos CD4 em crianças infectadas pelo HIV. CASUÍSTICA E MÉTODOS: A forma de estudo foi cross-sectional com 471 crianças infectadas pelo HIV. Em 1996, inibidores de protease foram liberados para terapia anti-retroviral. Dest...

  17. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice? : VF & Clinical Events by ART Regimen

    OpenAIRE

    Mugavero, Michael; May, Margaret; Harris, Ross; Saag, Michael,; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych; Dabis, Francois; Hogg, Robert; De Wolf, Frank; Fatkenheuer, Gerd; John Gill, M.; Justice, Amy; D'Arminio Monforte, Antonella

    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-na? patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between January 2000 and December 2005. SETTING: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. STUDY PARTICIPAN...

  18. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  19. Early severe HIV disease precedes early antiretroviral therapy in infants: Are we too late?

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    Steve Innes

    2014-06-01

    Full Text Available Objective: To describe the degree of HIV disease progression in infants initiating antiretroviral therapy (ART by three months of age in a programmatic setting in South Africa. Design: This was a programmatic cohort study. Methods: Electronic and manual data extraction from databases and antiretroviral registers in 20 public clinics in Cape Town and electronic data extraction from a large ART service at Chris Hani Baragwanath Hospital in Soweto were performed. Records of all infants initiated on ART by three months of age between June 2007 and September 2010 were extracted. Demographics, immunological and clinical stage at ART initiation were analyzed descriptively by chi-square, two-sample t-test and Kaplan–Meier methods. Results: A total of 403 records were identified: 88 in Cape Town and 315 in Soweto. Median age at ART initiation was 8.4 [interquartile range (IQR: 7.2–9.7] weeks. At ART initiation, 250 infants (62% had advanced HIV disease (CD4% <25% or absolute CD4<1500 cells/mm3 or WHO clinical Stage 3 or 4. Median age at ART initiation by site was 10.3 (IQR: 8.2–11.9 weeks in Cape Town and 8.6 (IQR: 7.7–10.0 weeks in Soweto infants (p<0.0001. In Cape Town, 73 infants (83% had advanced HIV disease at ART initiation, compared to 177 infants (56% in Soweto (p<0.0001. On logistic regression, each month increase in age at ART initiation lowered the odds of initiating ART in an optimal state (OR: 0.56, CI: 0.36–0.94 and increased the odds of advanced HIV disease at ART initiation (OR: 1.69, CI: 1.05–2.71. Conclusions: ART initiation by three months of age may not adequately prevent disease progression. New emphasis on early diagnosis and rapid initiation of ART in the first weeks of life are essential to further reduce infant mortality.

  20. Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey

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    Murat Sayan

    2014-11-01

    Full Text Available Introduction: The objective of this study was to determine the transmitted drug resistance mutations (TDRMs in newly diagnosed HIV-1 positive patients in Turkey. Materials and Methods: The study was carried out between 2009 and 2014 and antiretroviral naïve 774 HIV-1 infected patients from 19 Infectious Diseases and Clinical Microbiology Departments in Turkey were included; gender: 664 (86% male, median age: 37 (range; 1–77, median CD4+T-cell: 360 (range; 1–1320 count/mm3, median HIV-RNA load: 2.10+E6 (range; 4.2+E2–7.41+E8 IU/mL. HIV-1 drug resistance mutations were detected by population based sequencing of the reverse transcriptase (codon 41–238 and protease (codon 1–99 domains of pol gene of HIV-1, and analyzed according to the criteria by the World Health Organization 2009 list of surveillance drug resistance mutations [1]. Results: The patients had TDRMs to NRTIs (K65R, M184V, NNRTIs (K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M. The prevalence of overall TDRMs was 6.7% (52/774. Resistance mutations were found to be 0.7% (6/774, 4.1% (32/774 and 2.1% (17/774 to NRTIs, NNRTIs and PIs drug groups, respectively. Three patients had NRTIs+NNRTs resistance mutations (M184V+K103N as multi-class drug resistance. However, thymidine analogue resistance mutations (TAMs determined two distinct genotypic profiles in the HIV-1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q, and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774 and 4.3% (34/774, respectively. Conclusions: The TDRMs prevalence of antiretroviral naïve HIV-1 infected patients may be suggested current situation of Turkey. These long-term and large-scale results show that the resistance testing must be an integral part of the management of HIV infection in Turkey.

  1. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

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    R. Chris Rathbun

    2011-10-01

    Full Text Available Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450 and uridine diphosphate glucuronosyltransferase (UGT enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide. The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed.

  2. Early severe morbidity and resource utilization in South African adults on antiretroviral therapy

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    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.

  3. Adherence to antiretroviral therapy and its determinants among persons living with HIV/AIDS in Bayelsa state, Nigeria

    OpenAIRE

    Suleiman IA; Momo A

    2016-01-01

    Background: A high level of adherence is required to achieve the desired outcomes of antiretroviral therapy. There is paucity of information about adherence to combined antiretroviral therapy in Bayelsa State of southern Nigeria. Objectives: The objectives of the study were to determine the level of adherence to combined antiretroviral therapy among the patients, evaluate the improvement in their immune status and identify reasons for sub-optimal adherence to therapy. Methods: The cross...

  4. Impact of Adherence Counseling Dose on Antiretroviral Adherence and HIV Viral Load among HIV-Infected Methadone Maintained Drug Users

    OpenAIRE

    Cooperman, Nina A.; Heo, Moonseong; Berg, Karina M.; Li, Xuan; Litwin, Alain H.; Nahvi, Shadi; Arnsten, Julia H.

    2012-01-01

    Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy delivered in methadone clinics. Our adherence couns...

  5. Quality of life of People living with HIV and AIDS attending the Antiretroviral Clinic, University College Hospital, Nigeria

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    Oluyemisi F. Folasire

    2012-02-01

    Full Text Available Background: Quality of life (QOL is an important component in the evaluation of the well-being of people living with HIV and AIDS (PLWHA, especially with the appreciable rise in longevity of PLWHA. Moreover, limited studies have been conducted in Nigeria on how PLWHA perceive their life with the World Health Organisation Quality of Life Brief Scale (WHOQOL-Bref instrument. Objective: This study assessed the QOL of PLWHA attending the antiretroviral (ARV clinics, UCH Ibadan, Nigeria.Method: A cross-sectional study was conducted from June to September 2008 that involved 150 randomly selected HIV-positive patients who were regular attendees at the antiretroviral clinic, UCH Ibadan. An interviewer administered questionnaire was used to collect information on sociodemographic data, satisfaction with perceived social support, medical records, and QOL was assessed with WHOQOL-Bref.Results: The mean age of the respondents was 38.1 ± 9.0 years and the male : female ratio was 1:2. The mean CD4 count was higher in female patients than in male patients, 407 cells/mm3 : 329 cells/mm3 (p = 0.005. The mean QOL scores on the scale of (0–100 in three domains were similar: psychological health, 71.60 ± 18.40; physical health, 71.60 ± 13.90; and the environmental domain, 70.10 ± 12.00; with the lowest score in the social domain, 68.89 ± 16.70. Asymptomatic HIV-positive patients had significantly better mean QOL scores than symptomatic patients in the physical (74.04 ± 16.85 versus 64.47 ± 20.94, p = 0.005 and psychological domains (76.09 ± 12.93 versus 69.74 ± 15.79, p = 0.015. There was no significant difference in the mean QOL scores of men compared to those of women, in all domains assessed.Conclusion: High QOL scores in the physical, psychological and environmental domains may be reflective of the effectiveness of some of the interventions PLWHA are exposed to at the ARV clinic, UCH Ibadan (on-going psychotherapy, free antiretroviral drugs

  6. Antiretroviral Treatment and Sexual Risk Behavior in South Africa.

    Science.gov (United States)

    Risher, Kathryn; Rehle, Thomas; Simbayi, Leickness; Shisana, Olive; Celentano, David D

    2016-04-01

    The sexual behavior of individuals living with HIV determines the onward transmission of HIV. With the understanding that antiretroviral therapy (ART) prevents transmission of HIV, the sexual behaviors of the individuals not on ART with unsuppressed viral loads becomes of the greatest importance in elucidating transmission. We assessed the association between being on ART and sexual risk behavior among those living with HIV in a nationally representative population-based cross-sectional survey of households in South Africa that was conducted in 2012. Of 2237 adults (aged 15-49) who tested HIV-seropositive, 667 (29.8 %) had detectable antiretroviral drugs in their blood specimens. Among males, 77.7 % of those on ART reported having had sex in the past year contrasted with 88.4 % of those not on ART (p = 0.001); among females, 72.2 % of those on ART reported having had sex in the past year while 80.3 % of those not on ART did (p < 0.001). For males and females, the odds of reporting consistent condom use and condom use at last sex were statistically significantly higher for individuals on ART compared to those not on ART (males: consistent condom use aOR 2.8, 95 % CI 1.6-4.9, condom use at last sex aOR 2.6, 95 % CI 1.5-4.6; females: consistent condom use aOR 2.3, 95 % CI 1.7-3.1, condom use at last sex aOR 2.3, 95 % CI 1.7-3.1), while there were no statistically significant differences in odds of reporting multiple sexual partners in the past year. In this nationally representative population-based survey of South African adults, we found evidence of less risky sexual risk behavior among people living with HIV on ART compared to those not on ART. PMID:26194426

  7. Soluble urokinase receptor levels in plasma during 5 years of highly active antiretroviral therapy in HIV-1-infected patients

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo;

    2004-01-01

    High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highly...... active antiretroviral therapy (HAART). Plasma suPAR decreased after introducing HAART, most pronounced during the first treatment year. The change in plasma suPAR was independent of changes in viral replication and CD4+ cells but it was strongly correlated with plasma levels of the soluble TNF receptor...... II. Compared with healthy individuals, plasma suPAR and sTN-FrII was increased in untreated patients. After initiating HAART, plasma sTNFrII remained increased whereas plasma suPAR decreased to a level comparable with healthy individuals. The present data indicate that the circulating suPAR level is...

  8. Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy

    DEFF Research Database (Denmark)

    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...

  9. Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec; Lampe, Fiona C; Rodger, Alison; Nakagawa, Fumiyo; Brown, Alison; Gill, O Noel; De Angelis, Daniela; Elford, Jonathan; Hart, Graham; Johnson, Anne M; Lundgren, Jens D; Collins, Simon; Delpech, Valerie

    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. <535 new infections per year) by 2030, and whether this is likely to be cost-effective. METHODS: A dynamic, individual-based simulation model was calibrated to multiple data sources...... 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...

  10. Immune reconstitution inflammatory syndrome in HIV-infected patients receiving antiretroviral therapy : pathogenesis, clinical manifestations and management

    DEFF Research Database (Denmark)

    Dhasmana, Devesh J; Dheda, Keertan; Ravn, Pernille; Wilkinson, Robert J; Meintjes, Graeme

    2008-01-01

    The use of antiretroviral therapy (ART) to treat HIV infection, by restoring CD4+ cell count and immune function, is associated with significant reductions in morbidity and mortality. Soon after ART initiation, there is a rapid phase of restoration of pathogen-specific immunity. In certain patients......, this results in inflammatory responses that may result in clinical deterioration known as 'the immune reconstitution inflammatory syndrome' (IRIS). IRIS may be targeted at viable infective antigens, dead or dying infective antigens, host antigens, tumour antigens and other antigens, giving rise to a...... heterogeneous range of clinical manifestations. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. In most patients, ART should be continued and treatment for the associated condition optimized, and there is anecdotal evidence for the use of corticosteroids in...

  11. 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.

  12. 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

    Directory of Open Access Journals (Sweden)

    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.

  13. In silico modeling indicates the development of HIV-1 resistance to multiple shRNA gene therapy differs to standard antiretroviral therapy

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    Mcintyre Glen

    2010-10-01

    Full Text Available Abstract Background Gene therapy has the potential to counter problems that still hamper standard HIV antiretroviral therapy, such as toxicity, patient adherence and the development of resistance. RNA interference can suppress HIV replication as a gene therapeutic via expressed short hairpin RNAs (shRNAs. It is now clear that multiple shRNAs will likely be required to suppress infection and prevent the emergence of resistant virus. Results We have developed the first biologically relevant stochastic model in which multiple shRNAs are introduced into CD34+ hematopoietic stem cells. This model has been used to track the production of gene-containing CD4+ T cells, the degree of HIV infection, and the development of HIV resistance in lymphoid tissue for 13 years. In this model, we found that at least four active shRNAs were required to suppress HIV infection/replication effectively and prevent the development of resistance. The inhibition of incoming virus was shown to be critical for effective treatment. The low potential for resistance development that we found is largely due to a pool of replicating wild-type HIV that is maintained in non-gene containing CD4+ T cells. This wild-type HIV effectively out-competes emerging viral strains, maintaining the viral status quo. Conclusions The presence of a group of cells that lack the gene therapeutic and is available for infection by wild-type virus appears to mitigate the development of resistance observed with systemic antiretroviral therapy.

  14. Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

    DEFF Research Database (Denmark)

    Desmonde, Sophie; Eboua, François T; Malateste, Karen;

    2015-01-01

    BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric IeDEA clin...

  15. 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

  16. 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.

  17. Miliary tuberculosis in human immunodeficiency virus infected patients not on antiretroviral therapy: Clinical profile and response to shortcourse chemotherapy

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    Swaminathan S

    2007-01-01

    Full Text Available Background: An increase in tuberculosis (TB incidence has been associated with human immunodeficiency virus (HIV. Aims: To describe the clinical characteristics and treatment outcome of patients with HIV and miliary TB treated with short-course intermittent chemotherapy in the absence of access to highly active antiretroviral therapy (HAART. Settings and Design: Prospective study of HIV infected adults referred to a TB clinic between July 1999 and July 2004. Materials and Methods: On diagnosis of miliary TB, patients were treated with a standard regimen of two months of isoniazid, rifampicin, ethambutol and pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ 3 /4RH 3 thrice weekly and followed up for 24 months. Patients were reviewed clinically every month and two sputa were collected. Chest radiographs and blood investigations were done at two months, end of treatment and every six months thereafter. Results: Of 498 patients with HIV and tuberculosis, 31 (6% were diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for acid-fast bacilli (AFB in 14 patients (45% and Mycobacterium tuberculosis was isolated in 21 (68%. The mean CD4 cell count was 129 ± 125 cells/mm 3 . Twenty-five patients were declared cured at the end of treatment (81% while one (3% died and five (16% failed. The recurrence rate was 19.4/100 person-years and the median survival was 17 months (95% CI 14 to 20. None of the patients received antiretroviral therapy. Conclusions: Miliary TB tends to occur among HIV infected patients with severe immunosuppression. Though the initial response to short-course chemotherapy was encouraging, a high recurrence rate and mortality was observed indicating poor prognosis in HIV.

  18. Early initiation of antiretroviral therapy results in decreased morbidity and mortality among patients with TB and HIV

    Directory of Open Access Journals (Sweden)

    Tabarsi Payam

    2009-07-01

    Full Text Available Abstract Introduction The overlapping drug toxicity profiles, drug-drug interactions and complications of management of both HIV and tuberculosis (TB in patients with advanced HIV have not been fully delineated. Methods We conducted a retrospective chart review of the outcomes of tuberculosis treatment among 69 HIV-infected patients with TB, who were hospitalized in Masih Daneshvari Hospital in Tehran, Iran between 2002 and 2006, and who received standard category 1 (CAT-1 regimens. Group I (N = 47 included those treated from 2002 to 2005 with highly active antiretroviral therapy (HAART initiated after eight weeks of TB treatment for those whose CD4 count was 3. Group II (N = 22 included TB patients treated from 2005 to 2006, with HAART initiated after two weeks of TB treatment if their CD4 count was 3 and eight weeks after initiation of TB treatment for those whose CD4 count was between 101 and 200 cells/mm3. Results There were no differences between Groups I and II with regard to: adverse drug reactions [four (8.5% versus two (9%, p = ns]; IRIS [six (12.7% versus three (10.7%, p = ns]; and new opportunistic infections [eight (17.0% versus two (9.1%, p = ns]. Death, however, occurred more frequently in Group I than in Group II [13 (27.7% versus (4.5%, p = 0.03], where HAART was initiated earlier. Injection of drugs was the most common route of HIV transmission in both groups (72.3% in Group I and 77.3% in Group II. Conclusion This manuscript shows that in a retrospective review of HIV/TB patients hospitalized in Tehran, improved survival was associated with earlier initiation of antiretroviral therapy in HIV/TB patients with CD4 counts of below 100 cells/mm3.

  19. Preterm Birth and Low Birth Weight after In Utero Exposure to Antiretrovirals Initiated during Pregnancy in Yaoundé, Cameroon

    Science.gov (United States)

    Njom Nlend, Anne Esther; Nga Motazé, Annie; Moyo Tetang, Suzie; Zeudja, Cécile; Ngantcha, Marcus; Tejiokem, Mathurin

    2016-01-01

    Background Effects of antiretroviral therapy (ART) on birth outcomes remain controversial. Objective To assess the impact of antenatal exposure to ART on the occurrence of preterm birth (PTB) and low birth weight (LBW). Methods A cross-sectional study conducted at the Essos Hospital Center in Yaounde from 2008 to 2011 among HIV vertically exposed infants with two distinct maternal antiretroviral experiences: monotherapy group (Zidovudine, ZDV) and the combination ART group (cART). Mothers already receiving cART before pregnancy were ineligible. In both groups, events of PTB (<37 weeks) and LBW (<2,500g) were analyzed using univariate and multivariate logistic regression; with p<0.05 considered statistically significant. Results Of the 760 infants, 481 were born from cART-exposed mothers against 279 from maternal-ZDV. Median maternal CD4 count was 378 [interquartile range (IQR): 253–535] cells/mm3. Median duration of ART at onset of delivery was 13 [IQR: 10–17] weeks. In the cART-group, 64.9% (312/481) of mothers were exposed to Zidovudine/Lamuvidine/Nevirapine and only 2% (9/481) were on protease inhibitor-based regimens. Events of PTB were not significantly higher in the cART-group compared to the ZDV-group (10.2% vs. 6.4% respectively, p = 0.08), while onsets of LBW were significantly found in the cART-group compared to ZDV-group (11.6% vs. 7.2% respectively, p = 0.05). Other factors (parity, maternal age at delivery or CD4 cell count) were not associated with PTB. Conclusion cART, initiated during pregnancy, would be an independent factor of LBW. In the era of option B+ (lifelong ART to all HIV-pregnant women), further studies would guide towards measures limiting onsets of LBW. PMID:26999744

  20. Public health implications of antiretroviral therapy and HIV drug resistance.

    Science.gov (United States)

    Wainberg, M A; Friedland, G

    1998-06-24

    Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy. PMID:9643862

  1. ABC of AIDS and Antiretroviral Therapy: Perspectives and Obstacles

    Directory of Open Access Journals (Sweden)

    R.Ramakrishna

    2011-12-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 is undoubtedly the primary cause of the acquired immunodeficiency syndrome (AIDS, which is a slow, progressive and degenerative disease of the human immune system. The pathogenesis of HIV-1 is complex and characterized by the interplay of both viral and host factors. Practically every stage in the viral life cycle and every viral gene product is a potential target. Although HAART has made long-term suppression of HIV a reality, drug resistance, drug toxicity, drug penetration, adherence to therapy, low levels of continued viral replication in cellular reservoirs and augmentation of host immune responses are some of the most important challenges that remain to be sorted out. Novel targets for the management of HIV infection have become increasingly relevant in view of extensive drug resistance, side effects and high pill burden of some of the conventional anti-retroviral agents. These agents include chemokine receptor antagonists, integrase inhibitors, maturation inhibitors, zinc finger inhibitors, pharmacological CDK inhibitors, Tate-TAR interaction inhibitors, anti-CD4 monoclonal antibodies and antisense oligonucleotides. In this review we gave a basic overview of the virology of HIV-1 including the functions of the different HIV-1 proteins required for effective viral replication, various obstacles to HIV therapy, perspectives related to the issues that are critical in determining the success or failure of HAART, current methods for detecting HIV-1 drug resistance and various novel targets for the management of HIV infection

  2. Nurses' perceptions about Botswana patients' anti-retroviral therapy adherence

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    Valerie J. Ehlers

    2009-04-01

    Full Text Available Anti-retroviral drugs (ARVs are supplied free of charge in Botswana. Lifelong adherence to anti-retroviral therapy (ART is vital to improve the patient’s state of well-being and to prevent the development of strains of the human immunodef ciency virus (HIV that are resistant to ART. Persons with ART-resistant strains of HIV can spread these to other people, requiring more expensive ART with more severe side-effects and poorer health outcomes. The purpose of this exploratory, descriptive, qualitative study was to determine nurses’ perspectives on Botswana patients’ anti-retroviral therapy (ART adherence, and to identify factors which could promote or hinder ART adherence. Four ART sites were randomly selected and all 16 nurses providing ART services at these sites participated in semi-structured interviews. These nurses indicated that patients’ ART adherence was inf uenced by service-related and patient-related factors. Service-related factors included the inaccessibility of ART clinics, limited clinic hours, health workers’ inability to communicate in patients’ local languages, long waiting times at clinics and delays in being informed about their CD4 and viral load results. Nurses could not trace defaulters nor contact them by phone, and also had to work night shifts, disrupting nurse-patient relationships. Patient-related factors included patients’ lack of education, inability to understand the significance of CD4 and viral load results, financial hardships, non-disclosure and non-acceptance of their HIV positive status, alcohol abuse, the utilisation of traditional medicines and side effects of ART. The challenges of lifelong ART adherence are multifaceted involving both patient-related and service-related factors. Supplying free ARVs does not ensure high levels of ART adherence.

    Opsomming

    Anti-retrovirale middels (ARMs word gratis verskaf in Botswana. Lewenslange getroue nakoming van ARM voorskrifte is

  3. Namibian prisoners describe barriers to HIV antiretroviral therapy adherence.

    Science.gov (United States)

    Shalihu, Nauyele; Pretorius, Louise; van Dyk, Agnes; Vander Stoep, Ann; Hagopian, Amy

    2014-01-01

    Little is available in scholarly literature about how HIV-positive prisoners, especially in low-income countries, access antiretroviral therapy (ART) medication. We interviewed 18 prisoners at a large prison in Namibia to identify barriers to medication adherence. The lead nurse researcher was a long-standing clinic employee at the prison, which afforded her access to the population. We identified six significant barriers to adherence, including (1) the desire for privacy and anonymity in a setting where HIV is strongly stigmatized; (2) the lack of simple supports for adherence, such as availability of clocks; (3) insufficient access to food to support the toll on the body of ingesting taxing ART medications; (4) commodification of ART medication; (5) the brutality and despair in the prison setting, generally leading to discouragement and a lack of motivation to strive for optimum health; and (6) the lack of understanding about HIV, how it is transmitted, and how it is best managed. Because most prisoners eventually transition back to communitysettings when their sentences are served, investments in prison health represent important investments in public health. PMID:24499371

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure....... METHODS: Individuals with MDR HIV-1 receiving therapy for > or =3 months were included. CD4+ T-cell count slopes and pol and clonal env sequences were determined. Genetic analyses were performed using distance-based and maximum likelihood methods. Synonymous mutations rates of env were used to estimate...

  5. 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.

  6. 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

  7. Integration of antiretroviral therapy services into antenatal care increases treatment initiation during pregnancy: a cohort study.

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    Kathryn Stinson

    Full Text Available OBJECTIVES: Initiation of antiretroviral therapy (ART during pregnancy is critical to promote maternal health and prevent mother-to-child HIV transmission (PMTCT. The separation of services for antenatal care (ANC and ART may hinder antenatal ART initiation. We evaluated ART initiation during pregnancy under different service delivery models in Cape Town, South Africa. METHODS: A retrospective cohort study was conducted using routinely collected clinic data. Three models for ART initiation in pregnancy were evaluated ART 'integrated' into ANC, ART located 'proximal' to ANC, and ART located some distance away from ANC ('distal'. Kaplan-Meier methods and Poisson regression were used to examine the association between service delivery model and antenatal ART initiation. RESULTS: Among 14 617 women seeking antenatal care in the three services, 30% were HIV-infected and 17% were eligible for ART based on CD4 cell count <200 cells/µL. A higher proportion of women started ART antenatally in the integrated model compared to the proximal or distal models (55% vs 38% vs 45%, respectively, global p = 0.003. After adjusting for age and gestation at first ANC visit, women who at the integrated service were significantly more likely to initiate ART antenatally (rate ratio 1.33; 95% confidence interval: 1.09-1.64 compared to women attending the distal model; there was no difference between the proximal and distal models in antenatal ART initiation however (p = 0.704. CONCLUSIONS: Integration of ART initiation into ANC is associated with higher levels of ART initiation in pregnancy. This and other forms of service integration may represent a valuable intervention to enhance PMTCT and maternal health.

  8. PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection.

    Science.gov (United States)

    Welch, Steve; Sharland, Mike; Lyall, E G Hermione; Tudor-Williams, Gareth; Niehues, Tim; Wintergerst, Uwe; Bunupuradah, Torsak; Hainaut, Marc; Della Negra, Marinella; Pena, Maria José Mellado; Amador, José Tomas Ramos; Gattinara, Guido Castelli; Compagnucci, Alexandra; Faye, Albert; Giaquinto, Carlo; Gibb, Diana M; Gandhi, Kate; Forcat, Silvia; Buckberry, Karen; Harper, Lynda; Königs, Christoph; Patel, Deepak; Bastiaans, Diane

    2009-11-01

    PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained. PMID:19878352

  9. Metabolic syndrome in HIV-infected patients receiving antiretroviral therapy in Latin America

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    C Alvarez

    2010-06-01

    Full Text Available OBJECTIVE: To evaluate the prevalence of and the associated factors for metabolic syndrome (MS among Latin American HIV-infected patients receiving antiretroviral therapy (ART using baseline data from the RAPID II study. METHODS: A longitudinal study to evaluate the metabolic profile, cardiovascular disease (CVD risk and associated treatment practices to reduce this risk has been conducted in seven Latin American countries (the RAPID II study. Adult HIV patients with at least six months of RT were enrolled. MS was defined following ATP-III criteria. Demographic and anthropometric data, serum biochemical and clinical parameters were compared in patients with and without MS using bivariate and multivariate analysis. RESULTS: A total of 4,010 patients were enrolled, 2,963 (74% were males. Mean age (SD was 41.9 (10.0 years. The prevalence of MS was 20.2%. Females had higher prevalence of MS than males (22.7% vs. 19.4%, p = 0.02. MS was driven by high triglycerides, low HDL-cholesterol and high blood pressure (HBP. Patients with MS had higher 10year CVD risk: 22.2% vs. 7.4%, p < 0.001. Age (OR: 1.05 per year, female gender (OR: 1.29, family history of CVD (OR: 1.28, CD4 cell count (OR: 1.09 per 100 cell increase, and protease inhibitor based-ART (OR: 1.33 correlated with MS in the multivariate analysis. CONCLUSIONS: Prevalence of MS in this setting was similar to that reported from developed countries. MS was driven by high triglycerides, low-HDL and HBP, and it was associated with higher risk of CVD. Traditional risk factors, female gender, immune reconstitution, and protease inhibitor based-ART correlated with MS.

  10. 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.

  11. Protease inhibitors effectively block cell-to-cell spread of HIV-1 between T cells

    OpenAIRE

    Titanji, Boghuma; Aasa-Chapman, Marlen; Pillay, Deenan; Jolly, Clare

    2013-01-01

    Background; The Human Immunodeficiency Virus type-1 (HIV-1) spreads by cell-free diffusion and by direct cell-to-cell transfer, the latter being a significantly more efficient mode of transmission. Recently it has been suggested that cell-to-cell spread may permit ongoing virus replication in the presence of antiretroviral therapy (ART) based on studies performed using Reverse Transcriptase Inhibitors (RTIs). Protease Inhibitors (PIs) constitute an important component of ART; however whether ...

  12. Adherence to antiretrovirals in people coinfected with the human immunodeficiency virus and tuberculosis1

    Science.gov (United States)

    Lemos, Larissa de Araújo; Fiuza, Maria Luciana Teles; Reis, Renata Karina; Ferrer, André Carvalho; Gir, Elucir; Galvão, Marli Teresinha Gimeniz

    2016-01-01

    Objective: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. Method: cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. Results: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). Conclusion: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics. PMID:27192416

  13. Self-reported adverse reactions among patients initiating antiretroviral therapy in Brazil

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    Cristiane A. Menezes de Pádua

    2007-02-01

    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.

  14. Patient retention and adherence to antiretrovirals in a large antiretroviral therapy program in Nigeria: a longitudinal analysis for risk factors.

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    Man Charurat

    Full Text Available BACKGROUND: Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU and non-adherence to ART in a large treatment cohort in Nigeria. METHODS AND FINDINGS: We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p 350 and 2 hours to the clinic (p = 0.03, had total ART duration of >6 months (p200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01 and were treated with tenofovir-containing regimens (p < or = 0.001 were more likely to be adherent. CONCLUSIONS: These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence.

  15. 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.

  16. Antiretroviral treatment response of HIV-infected children after prevention of mother-to-child transmission in West Africa

    DEFF Research Database (Denmark)

    Ndondoki, Camille; Dicko, Fatoumata; Ahuatchi Coffie, Patrick;

    2014-01-01

    INTRODUCTION: We assessed the rate of treatment failure of HIV-infected children after 12 months on antiretroviral treatment (ART) in the Paediatric IeDEA West African Collaboration according to their perinatal exposure to antiretroviral drugs for preventing mother-to-child transmission (PMTCT). ...

  17. A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy

    NARCIS (Netherlands)

    D. Bezemer; F. de Wolf; M.C. Boerlijst; A. van Sighem; T.D. Hollingsworth; M. Prins; R.B. Geskus; L. Gras; R.A. Coutinho; C. Fraser

    2008-01-01

    Objective: Reducing viral load, highly active antiretroviral therapy has the potential to limit onwards transmission of HIV-1 and thus help contain epidemic spread. However, increases in risk behaviour and resurgent epidemics have been widely reported post-highly active antiretroviral therapy. The a

  18. 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...

  19. Drug-Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation : A Review

    NARCIS (Netherlands)

    van Maarseveen, Erik M.; Rogers, Christin C.; Trofe-Clark, Jennifer; van Zuilen, Arjan D.; Mudrikova, Tania

    2012-01-01

    Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive ther

  20. Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study

    DEFF Research Database (Denmark)

    Tavel, Jorge A; Babiker, Abdel; Fox, Lawrence;

    2010-01-01

    BACKGROUND: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4(+) counts compared to no therapy. METHODOLOGY: Participants not on continuous ART...

  1. 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; Geskus, Ronald; Perez-Hoyos, Santiago; Meyer, Laurence; Prins, Maria; Touloumi, Giota; Johnson, Anne; Hamouda, Osamah; de Olalla, Patricia García; Porter, Kholoud; del Amo, Julia; Kirk, Ole

    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)....

  2. Pregnancy and virologic response to antiretroviral therapy in South Africa.

    Directory of Open Access Journals (Sweden)

    Daniel Westreich

    Full Text Available BACKGROUND: Although women of reproductive age are the largest group of HIV-infected individuals in sub-Saharan Africa, little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART in that setting. We examined the effect of incident pregnancy after HAART initiation on virologic response to HAART. METHODS AND FINDINGS: We evaluated a prospective clinical cohort of adult women who initiated HAART in Johannesburg, South Africa between 1 April 2004 and 30 September 2009, and followed up until an event, death, transfer, drop-out, or administrative end of follow-up on 31 March 2010. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study; final sample size for analysis was 5,494 women. Main exposure was incident pregnancy, experienced by 541 women; main outcome was virologic failure, defined as a failure to suppress virus to ≤ 400 copies/ml by six months or virologic rebound >400 copies/ml thereafter. We calculated adjusted hazard ratios using marginal structural Cox proportional hazards models and weighted lifetable analysis to calculate adjusted five-year risk differences. The weighted hazard ratio for the effect of pregnancy on time to virologic failure was 1.34 (95% confidence limit [CL] 1.02, 1.78. Sensitivity analyses generally confirmed these main results. CONCLUSIONS: Incident pregnancy after HAART initiation was associated with modest increases in both relative and absolute risks of virologic failure, although uncontrolled confounding cannot be ruled out. Nonetheless, these results reinforce that family planning is an essential part of care for HIV-positive women in sub-Saharan Africa. More work is needed to confirm these findings and to explore specific etiologic pathways by which such effects may operate.

  3. Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings

    Directory of Open Access Journals (Sweden)

    Kevin Peterson

    2011-01-01

    Full Text Available HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations.

  4. 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......: Virologic response (viral load < 500 copies/mL) 6 to 12 months after starting cART was analyzed in antiretroviral-naive EuroSIDA patients. Analyses were stratified by region (south, central west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). RESULTS: Virologic...... time (P < 0.001) on virologic response after adjustment for confounders. Stratified by period, regional differences were less evident (early cART, P = 0.967; mid cART, P = 0.291; late cART, P = 0.163). Stratified by region, temporal changes were observed (south, P = 0.061; central west, P < 0...

  5. A one-year clinical trial using didanosine, stavudine and nevirapine for highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hua-ying; ZHENG Yu-huang; ZHANG Chun-ying; DING Pei-pei; ZOU Wen

    2005-01-01

    @@ Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.

  6. Immunological profile in persons under antiretroviral therapy in a rural Nigerian hospital

    Directory of Open Access Journals (Sweden)

    Baba Maiyaki Musa

    2010-09-01

    Full Text Available Human immunodeficiency virus (HIV contributes significantly to morbidity and mortality in sub-Saharan Africa, with Nigeria having the third highest burden of HIV infection globally; efforts are made to increases access to HIV/AIDS care and treatment. This has currently reached rural areas with limited manpower and laboratory evaluation capacity. This review is necessitated by the paucity of interim report on treatment profile in Nigerian rural areas. We report on the immunological profile of patients on antiretroviral therapy (ART in Otukpo General Hospital, a rural Nigerian hospital. This is a retrospective cohort study of patients receiving ART treatment and care, on April 2009, when 2347 patients were under ART therapy. Out of these, 96 patients were selected by simple random sampling from hospital register, with their data abstracted from standardized Ministry of Health registers and facility documents kept at the hospital, and analyzed for descriptive and biometric measures. Ninty-six patients (29% males with a median age of 35 years, median baseline CD4 lymphocyte count 221 cells/mL, median one year CD4 lymphocyte count of 356 cells/mL and median one year CD4 lymphocyte increment of 124 cells/mL were studied. There is no statistically significant difference in baseline CD4 lymphocyte count when data is disaggregated by type of drug regimen (AZT, D4T and TDF. Fourty-four percent, 23% and 33% of patients were on TDF, D4T & AZT based regimen, respectively (P=0.66. Increment of >100 cells/mL was seen in 64.58% of the reviewed patients. There was a higher CD4 lymphocyte count increment in patients on TDF & D4T compared with those in AZT based regimens (ANOVA; P<0.0003. Multivariate linear regression model showed one year CD4 lymphocyte count, one year increment in CD4 lymphocyte count, WBC count, and absolute neutrophil count to be significant correlates of baseline CD4 lymphocyte count (P<0.0001. Equally, multivariate logistic regression found

  7. Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti.

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    Serena P Koenig

    2011-09-01

    Full Text Available BACKGROUND: In a randomized clinical trial of early versus standard antiretroviral therapy (ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. METHODS AND FINDINGS: Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS, including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART and US$979 (standard ART. Early ART patients had higher mean costs for ART (US$398 versus US$81 but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384. The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS-US$9,979/YLS including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS-US$5,537/YLS. CONCLUSIONS: Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita after a maximum of 3 years, after excluding research-related laboratory tests. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120510.

  8. Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

    Science.gov (United States)

    Koenig, Serena P.; Bang, Heejung; Severe, Patrice; Jean Juste, Marc Antoine; Ambroise, Alex; Edwards, Alison; Hippolyte, Jessica; Fitzgerald, Daniel W.; McGreevy, Jolion; Riviere, Cynthia; Marcelin, Serge; Secours, Rode; Johnson, Warren D.; Pape, Jean W.; Schackman, Bruce R.

    2011-01-01

    Background In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. Methods and Findings Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS). Conclusions Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests. Trial registration ClinicalTrials.gov NCT00120510 Please see

  9. Nurse led, primary care based antiretroviral treatment versus hospital care: a controlled prospective study in Swaziland

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    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.

  10. Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomized trial

    DEFF Research Database (Denmark)

    Kirk, O; Katzenstein, T L; Gerstoft, J; Mathiesen, Lars Reinhardt; Nielsen, H; Pedersen, C; Lundgren, Jens Dilling

    1999-01-01

    missing values were accounted for as failures. RESULTS: As of 1 May 1998, 269 patients should have completed 24 weeks of treatment. The proportion of patients with HIV RNA of 200 copies/ml or less was 71% (indinavir), 67% (ritonavir), and 82% (ritonavir + saquinavir), P = 0.07. In antiretroviral drug...... generally safe, and has superior short-term antiviral efficacy compared with indinavir and ritonavir also combined with two nucleoside analogues in antiretroviral drug-naive patients. Further follow-up is needed to determine the durability of the viral response....

  11. 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...... provided, they were not always accessible for women in need. A variety of factors at the population and health system level interacted in ways that often made access to ARV drugs a complicated and time-consuming process. We have suggested changes that could be made at the health system level that may help...

  12. NOVEL DELIVERY SYSTEM ENHANCES EFFICACY OF ANTIRETROVIRAL THERAPY IN ANIMAL MODEL FOR HIV-1 ENCEPHALITIS (HIVE)

    OpenAIRE

    Spitzenberger, Timothy J.; Heilman, David; Diekmann, Casey; Batrakova, Elena; Kabanov, Alexander; Gendelman, Howard E.; Elmquist, William F.; Persidsky, Yuri

    2006-01-01

    Most potent anti-retroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of anti-retroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). SCID mice inoculated with HIV-1 infected human monocyt...

  13. Changes in CSF and plasma HIV-1 RNA and cognition after starting potent antiretroviral therapy

    OpenAIRE

    Marra, C.M.; Lockhart, D.; Zunt, J. R.; Perrin, M.; Coombs, R.W.; Collier, A.C.

    2003-01-01

    The authors assessed CSF and plasma HIV-1 RNA and neuropsychological test performance (composite neuropsychological test Z score [NPZ-4]) in 25 HIV-1–infected subjects 4 and 8 weeks after beginning potent antiretroviral therapy that included a protease inhibitor. In the 14 subjects who entered the study on no antiretroviral treatment, NPZ-4 improvement was associated with decline in CSF HIV-1 RNA at both visits (p = 0.001 and p = 0.02), and those treated with zidovudine or indinavir had great...

  14. Anemia in Antiretroviral Naïve HIV/AIDS Patients: A Study from Eastern India

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    Arindam Pande

    2012-01-01

    Full Text Available Background: Hematological manifestations are common throughout the course of HIV infection. Impact of anemia is the most significant among them. The present study was undertaken to evaluate the etiologies underlying anemia in HIV/AIDS. Methods This was a non randomized cross sectional observational study conducted in a tertiary care hospital of India over a period of 2 years. One hundred and fifty HIV patients were screened. Thorough clinical and laboratory evaluation was done in 50 randomly selected anemic cases. Results: Proper etiological diagnosis could be reached in 46 patients. Among them correlation between Hb% and CD4 count was statistically insignificant (p = 0.074, r = 0.47 whereas it was significant with absolute lymphocyte and CD4 count (p = 0.006, r = 0.41. There was better correlation of bone marrow iron status with percent saturation of transferrin (p = 0.003, r = 0.54 than with serum ferritin (p = 0.055, r = 0.09. Bone marrow iron status did not have any relationship with CD4 count. Anemia of chronic disease was the commonest etiology (37% followed by HIV related myelodysplastic syndrome (31%, iron deficiency anemia (13%, bone marrow suppression due to direct involvement by some infective process (7%. Aplastic anemia, multiple myeloma, Hodgkin’s disease, pure red cell aplasia, hemophagocytic lymphohistiocytosis and vitamin B12 deficiency were detected in one case (2% each. Conclusions: Etiologies of anemia in HIV/AIDS are multifactorial with anemia of chronic disease being the commonest. For screening of iron deficiency in this group, percent saturation is a better tool than serum ferritin. Absolute lymphocyte count can sometimes be used as a surrogate marker of immunological status in antiretroviral naïve HIV patients, particularly in resource poor areas.

  15. The functional status of patients with AIDS attending antiretroviral treatment center

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    T J Thejus

    2009-01-01

    Full Text Available Aims: To assess the functional status of patients with Acquired immunodeficiency syndrome (AIDS registered in the Anti-Retroviral Treatment (ART center. Materials and Methods: Design: Descriptive study. Study setting: ART center in Calicut Medical College, Kerala, India. Subjects: Cohorts of AIDS patients attending the ART center during the year 2007. Data collection: Done prospectively from the secondary data available from the center. Outcome measures: The demographic, morbidity, functional status and laboratory parameters were collected. Data processing was done using Excel datasheet and analysis were done using Epi info 2003. Results: One hundred and ninety-five patients received care during this period; 69% were males. The mean age was 38±9 years; 80% of them were married and in 50% of their spouses also tested positive for HIV. The mean CD4 count was 127 cells/microliter. The majority (90% were categorized as WHO Stage 3 or 4 of HIV. Only 52% of them were able to perform their usual work in or outside their house; the rest were not able to lead an economically productive life. Thirty-six per cent were only able to perform activities of daily living; 12% were bedridden.The functional status of the patients positively correlated with WHO disease stage ( P = < 0-0001, and CD4 count and hemoglobin levels negatively correlated with staging ( P = < 0.001. 62% are having any of the opportunistic infections. Conclusion: Fifty per cent of the AIDS patients are disabled and need support and care. As AIDS is a growing problem, community-based palliative care for AIDS patients should be strengthened in India.

  16. Antiretroviral therapy (ART management of Low-Level Viremia in Taiwan (ALLEVIATE

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    Chien-Yu Cheng

    2014-11-01

    Full Text Available Introduction: This retrospective study aimed to investigate that if switch of combination antiretroviral therapy (cART would result in viral suppression (20 to 5 log10 (% (59.4% (61.3% (54.3% .480 CD4 at LLV, median (range, cells/uL (63–1092 (63–1092 (134–1010 .156 PVL at enrollment, copies/mL (21–999 (21–939 (21–999 .002 PVL of 20–199 (% (77.0% (84.0% (58.7% .001 PVL of 200–999 (% (23.0% (16.0% (41.3% .001 Duration of cART exposure, median (range, weeks (12–391 (15–321 (12–391 .062 Years of HIV diagnosed, median, (range, years (1–14 (1–14 (2–13 .356 Ever treatment failure (% /165 /119 /46 .111 Current cART NRTIs+nNRTI (23.6% (32.8% (0% <0.001 NRTIs+PI (18.8% (24.4% (4.3% .003 NRTIs+PI/r (51.5% (39.5% (82.6% <0.001 NRTIs+II (4.2% (3.3% (6.5% .967 II+PI/r (1.8% (0% (6.5% .021 Conclusions: According to the clinical guidelines of BHIVA, patients with low-level viremia who switched to cART consisting of 2 NRTIs plus boosted PI or newer mechanisms were more likely to re-establish viral suppression to <40 copies/mL at week 48.

  17. 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

    2016-05-01

    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. PMID:26698540

  18. Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

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    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.

  19. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    International Nuclear Information System (INIS)

    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-PGF2α) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF2α 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 culminate

  20. Antiretroviral medications disrupt microglial phagocytosis of β-amyloid and increase its production by neurons: Implications for HIV-associated neurocognitive disorders

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    Giunta Brian

    2011-06-01

    Full Text Available Abstract Up to 50% of long-term HIV infected patients, including those with systemically well-controlled infection, commonly experience memory problems and slowness, difficulties in concentration, planning, and multitasking. Deposition of Aβ plaques is also a common pathological feature of HIV infection. However, it is not clear whether this accumulation is due to AD-like processes, HIV-associated immunosuppression, Tat protein-induced Aβ elevations, and/or the effects of single highly active antiretroviral therapy (ART. Here we evaluated the effects of several ART medications (Zidovudine, Lamivudine, Indinavir, and Abacavir alone and in combination on: 1 Aβ1-40, 42 generation in murine N2a cells transfected with the human "Swedish" mutant form of APP; 2 microglial phagocytosis of FITC-Aβ1-42 peptides in cultured murine N9 microglia. We report for the first time that these antiretroviral compounds (10 μM generally increase Aβ generation (~50-200% in SweAPP N2a cells and markedly inhibit microglial phagocytosis of FITC-Aβ1-42 peptides in murine microglia. The most significant amyloidogenic effects were observed with combined ART (p in vitro studies, these findings raise the possibility that ART may play a casual role in the elevated Aβ found in the brains of those infected with HIV. Therefore these compounds may consequently contribute to cognitive decline observed in HIV associated neurocognitive disorders (HAND.

  1. Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus.

    Science.gov (United States)

    Tau, Pamela; Mancon, Alessandro; Mileto, Davide; Di Nardo Stuppino, Silvia; Bottani, Giulia; Gismondo, Maria Rita; Galli, Massimo; Micheli, Valeria; Rusconi, Stefano

    2014-05-01

    HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/μl). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/μl and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus. PMID:24279648

  2. Prevalence, correlates and under-diagnosis of clinical depression among adults on highly active antiretroviral therapy in a Tertiary Health Institution in northeastern Nigeria

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    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.

  3. Predictors of change in CD4 lymphocyte count and weight among HIV infected patients on anti-retroviral treatment in Ethiopia: a retrospective longitudinal study.

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    Ayalu A Reda

    Full Text Available BACKGROUND: 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. OBJECTIVE: To determine the predictors of change in CD4 lymphocyte count and weight among HIV/AIDS infected patients taking antiretroviral treatment in eastern Ethiopia. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

  4. Maximizing the benefits of antiretroviral therapy for key affected populations

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    Ian R Grubb

    2014-07-01

    Full Text Available Introduction: Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART, and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion: Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions: Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including

  5. Designing Equitable Antiretroviral Allocation Strategies in Resource-Constrained Countries

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    Wilson David P

    2005-01-01

    Full Text Available Background 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. Methods and Findings 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

  6. Factors associated with suboptimal adherence to antiretroviral therapy in Asia

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    Awachana Jiamsakul

    2014-05-01

    Full Text Available 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

  7. Prevalence of parasitemia and associated immunodeficiency among HIV-malaria co-infected adult patients with highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    Caroline E Omoti; Chiedozie K Ojide; Patrick V Lofor; Emeka Eze; Joy C Eze

    2013-01-01

    Objective:To investigate the malaria parasitemia,CD4+ cell counts and some haematological indices amongHIV-malaria co-infected adult patients with highly active antiretroviral therapy (HAART).Methods:A total of342 adultHIV positive subjects were recruited at the consultant outpatientHIV/AIDS clinic,University ofBeninTeachingHospital,BeninCity,Nigeria between June2011 toNovember2011.Blood samples were taken for malaria parasite count,CD4+ cell count and other haematological counts.Results:Out of the342 adultHIV positive subjects a total of254 patients (74.3%) were found to have malaria parasitemia.The incidence of malaria parasitemia increased with advancing clinical stage ofHIV infection and this was statistically significant (P=0.002).There was no statistical significance when gender was compared with the HIV-malaria status (P>0.05).Of the254 co-infected patients,134 (52.8%) had high parasitemia (>1.25×109/L).Sixty patients were found to be hyperparasitemic (>2.5 parasites/L).There was a significant association betweenCD4+ cell count and having significant parasitemia (P 0.05).Conclusions:The prevalence of parasitemia is high among theHIV/AIDS infected patients.

  8. Antiretroviral-Related Adipocyte Dysfunction and Lipodystrophy in HIV-Infected Patients: Alteration of the PPARγ-Dependent Pathways

    Directory of Open Access Journals (Sweden)

    Martine Caron

    2009-01-01

    Full Text Available Lipodystrophy and metabolic alterations are major complications of antiretroviral therapy in HIV-infected patients. In vitro studies using cultured murine and human adipocytes revealed that some protease inhibitors (PIs and nucleoside reverse transcriptase inhibitors (NRTIs were implicated to a different extent in adipose cell dysfunction and that a chronic incubation with some PIs decreased mRNA and protein expression of PPARγ. Defective lamin A maturation linked to PI inhibitory activity could impede the nuclear translocation of SREBP1c, therefore, reducing PPARγ expression. Adipose cell function was partially restored by the PPARγ agonists, thiazolidinediones. Adverse effects of PIs and NRTIs have also been reported in macrophages, a cell type that coexists with, and modulates, adipocyte function in fat tissue. In HIV-infected patients under ART, a decreased expression of PPARγ and of PPARγ-related genes was observed in adipose tissue, these anomalies being more severe in patients with ART-induced lipoatrophy. Altered PPARγ expression was reversed in patients stopping PIs. Treatment of patients with agonists of PPARγ could improve, at least partially, the subcutaneous lipoatrophy. These data indicate that decreased PPARγ expression and PPARγ-related function, resulting from ART-induced adipose tissue toxicity, play a central role in HIV-related lipoatrophy and metabolic consequences.

  9. 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.

  10. Antiretroviral activity of the aminothiol WR1065 against Human Immunodeficiency virus (HIV-1 in vitro and Simian Immunodeficiency virus (SIV ex vivo

    Directory of Open Access Journals (Sweden)

    Borojerdi Jennifer P

    2009-11-01

    Full Text Available Abstract Background WR1065 is the free-thiol metabolite of the cytoprotective aminothiol amifostine, which is used clinically at very high doses to protect patients against toxicity induced by radiation and chemotherapy. In an earlier study we briefly reported that the aminothiol WR1065 also inhibits HIV-1 replication in phytohemagglutinin (PHA-stimulated human T-cell blasts (TCBs infected in culture for 2 hr before WR1065 exposure. In this study we expanded the original observations to define the dose-response curve for that inhibition, and address the question of additive effects for the combination of WR1065 plus Zidovudine (AZT. Here we also explored the effect of WR1065 on SIV by examining TCBs taken from macaques with well-established infections several months with SIV. Results TCBs from healthy human donors were infected for 2 hr with HIV-1, and viral replication (p24 was measured after 72 hr of incubation with or without WR1065, AZT, or both drugs. HIV-1 replication, in HIV-1-infected human TCBs, was inhibited by 50% at 13 μM WR1065, a dose at which 80% of the cells were viable. Cell cycle parameters were the same or equivalent at 0, 9.5 and 18.7 μM WR1065, showing no drug-related toxicity. Combination of AZT with WR1065 showed that AZT retained antiretroviral potency in the presence of WR1065. Cultured CD8+ T cell-depleted PHA-stimulated TCBs from Macaca mulatta monkeys chronically infected with SIV were incubated 17 days with WR1065, and viral replication (p27 and cell viability were determined. Complete inhibition (100% of SIV replication (p27 was observed when TCBs from 3 monkeys were incubated for 17 days with 18.7 μM WR1065. A lower dose, 9.5 μM WR1065, completely inhibited SIV replication in 2 of the 3 monkeys, but cells from the third macaque, with the highest viral titer, only responded at the high WR1065 dose. Conclusion The study demonstrates that WR1065 and the parent drug amifostine, the FDA-approved drug Ethyol, have

  11. A systematic literature review examining soluble and cellular biomarkers in HIV patients receiving antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    M Byrnes

    2012-11-01

    Full Text Available The use of antiretroviral therapies (ART for treatment of human immunodeficiency virus type 1 (HIV-1 has led to more favorable prognoses for infected individuals, including reduced HIV viral load, improved CD4 + T-cell recovery, and slower disease progression. However, ART-treated HIV+patients may have increased risk of adverse outcomes associated with chronic inflammation and immune activation. Molecules associated with chronic immune system activation and inflammatory cytokine production may be useful biomarkers of HIV pathogenesis and/or ART outcomes. We systematically identified MEDLINE-indexed articles published in the past decade investigating the association of several soluble (IL-6, CRP, MCP-1, IP-10, D-dimer, soluble CD14, and LPS and cellular (CD28, CD38, HLA-DR, PD-1, caspase-3, IFNγ and IL-2 ELISpots biomarkers with clinical outcomes in ART-treated HIV positive (HIV+ patients. Seventy publications were included, consisting mainly of observational studies of soluble biomarkers. One quartile elevations in baseline IL-6, CRP, and D-dimer were associated with increased risk of disease progression or death (ORs 1.8–2.4; p≤0.01 and all-cause mortality (ORs 4.1–5.3; p≤0.0001; these elevations were also associated with increased rates of IRIS (ORs 1.59–2.07; p≤0.001. Additionally, IL-6, CRP, and D-dimer levels were higher in patients who experienced a cardiovascular event than in controls (p≤0.001. The association between soluble biomarkers and quantitative assessments of HIV viral load has not been studied as thoroughly. However, several studies found an association between D-dimer and viral load. Research is lacking regarding the relationship between CD4 count and soluble biomarkers. Most studies evaluating cellular biomarkers examined their association with HIV viral load and CD4 count, but did not examine clinical outcomes. The most commonly studied cellular biomarkers were the T cell activation markers CD38 and HLA

  12. 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

  13. HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 sub-group analysis

    Directory of Open Access Journals (Sweden)

    Cynthia Brinson

    2014-11-01

    Full Text Available Introduction: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into the host CD4+ T-cell. AI438011 is a Phase IIb, randomized, active-controlled trial investigating the safety, efficacy and dose–response of BMS-663068 versus atazanavir/ritonavir (ATV/r in treatment-experienced (TE, HIV-1-positive subjects. Materials and Methods: Antiretroviral TE subjects (exposure to ≥1 antiretroviral for ≥1 week with susceptibility to all study drugs (BMS-626529 IC50 100 nM, were randomized equally to four BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD and a control group (ATV/r 300/100 mg QD with tenofovir disoproxil fumarate (TDF + raltegravir (RAL. A sub-group analysis of viral efficacy and immunologic reconstitution is presented. Results: A total of 251 subjects were treated. Median age was 39 years, 60% were male and 38% were white. Median baseline (BL viral load (VL was 4.85 log10 c/mL (43%; 100,000 c/mL and median CD4+ T-cell count was 230 cells/mm3 (38%; 200 CD4 cells/mm3. Through Week 24, response rates (HIV-1 RNA 50 c/mL were comparable across all BMS-663068 arms and the ATV/r arm regardless of gender, age and race. Response rates for subjects with BL VL 100,000 c/mL (BMS-663068, 82-96%; ATV/r, 93% were higher than those for subjects with BL VL ≥100,000 c/mL (BMS-663068, 70-87%; ATV/r, 73%; however, there were no substantial differences in response across the BMS-663068 and ATV/r arms in either sub-group. Response rates for subjects with BL CD4+ cell counts ≥200 cells/mm3 (87-96% were higher than those for subjects with BL CD4+ cell counts 200 cells/mm3 (62–82%; however, no substantial differences in response were seen across the BMS-663068 and ATV/r arms in either sub-group. Mean changes in CD4+ T-cell counts from BL were similar across all arms regardless of gender, age and BL CD4+ T-cell count. Conclusion: Virologic response rates

  14. Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy

    NARCIS (Netherlands)

    F. van Leth; B.S. Kappelhoff; D. Johnson; M.H. Losso; A. Boron-Kaczmarska; M.S. Saag; J.M. Livrozet; D.B. Hall; J. Leith; A.D.R. Huitema; F.W. Wit; J.H. Beijnen; J.M.A. Lange

    2006-01-01

    Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (C-min) and total drug exposure over 24 hr (AUC(24)) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the

  15. Evaluation of antiretroviral drug measurements by an interlaboratory quality control program.

    NARCIS (Netherlands)

    Droste, J.A.H.; Aarnoutse, R.E.; Koopmans, P.P.; Hekster, Y.A.; Burger, D.M.

    2003-01-01

    Since 1999 an ongoing international interlaboratory quality control program has analyzed antiretroviral drugs in plasma. Results of the third round of this program are presented. Quality control samples were prepared by spiking drug-free plasma with varying concentrations of the currently available

  16. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel

    NARCIS (Netherlands)

    Gunthard, H.F.; Aberg, J.A.; Eron, J.J.; Hoy, J.F.; Telenti, A.; Benson, C.A.; Burger, D.M.; Cahn, P.; Gallant, J.E.; Glesby, M.J.; Reiss, P.; Saag, M.S.; Thomas, D.L.; Jacobsen, D.M.; Volberding, P.A.

    2014-01-01

    IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when

  17. Transmitted antiretroviral drug resistance among newly HIV-1 diagnosed young individuals in Kampala

    NARCIS (Netherlands)

    N. Ndembi; R.L. Hamers; K.C.E. Sigaloff; F. Lyagoba; B. Magambo; B. Nanteza; C. Watera; P. Kaleebu; T.F. Rinke de Wit

    2011-01-01

    To assess the emergence of transmitted HIV-1 drug resistance (TDR) in Kampala, Uganda, 10 years after the scale-up of antiretroviral treatment (ART) and to compare with a previous survey among antenatal clinic attendees in 2007 (reporting 0% TDR). A cross-sectional survey was conducted among newly H

  18. Evaluation of antiretroviral therapy results in a resource-poor setting in Blantyre, Malawi.

    NARCIS (Netherlands)

    Oosterhout, J.J. van; Bodasing, N.; Kumwenda, J.J.; Nyirenda, C.; Mallewa, J.; Cleary, P.R.; Baar, M.P. de; Schuurman, R.; Burger, D.M.; Zijlstra, E.E

    2005-01-01

    OBJECTIVE: To evaluate treatment results of the paying antiretroviral therapy (ART) clinic of Queen Elizabeth Central Hospital, a large public and teaching hospital in Blantyre, Malawi. The only ART was a fixed drug combination of stavudine, lamivudine and nevirapine. METHODS: Cross sectional study

  19. Changes in lipids and lipoprotein particle concentrations after interruption of antiretroviral therapy

    DEFF Research Database (Denmark)

    Lampe, Fiona C; Duprez, Daniel A; Kuller, Lewis H;

    2010-01-01

    The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management of...

  20. New Insights into HIV-1 Persistence in Sanctuary Sites During Antiretroviral Therapy.

    Science.gov (United States)

    Poveda, Eva; Tabernilla, Andrés

    2016-01-01

    Current combinations of antiretroviral drugs for the treatment of HIV infection can successfully achieve and maintain long-term suppression of HIV-1 replication in plasma. Still, none of these therapies is capable of eradicating the virus from the long-lived cellular reservoir that represents the major barrier to HIV cure. PMID:27028272

  1. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging.

    Science.gov (United States)

    Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

    2015-01-01

    While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets. PMID:26273190

  2. Plasma cytokine levels in Tanzanian HIV-1-infected adults and the effect of antiretroviral treatment

    DEFF Research Database (Denmark)

    Haissman, J.M.; Vestergaard, L.S.; Sembuche, S.;

    2009-01-01

    OBJECTIVE: To evaluate the role immune activation leading to the production and circulation of cytokines has in the pathogenesis of HIV infection in sub-Saharan Africa and the effect of antiretroviral treatment (ART) on these parameters. METHODS: Plasma concentrations of tumor necrosis factor (TN...

  3. Antiretroviral treatment among co-infected tuberculosis patients in integrated and non-integrated facilities

    OpenAIRE

    Ledibane, T. D.; Motlhanke, S. C.; Rose, A; Kruger, W. H.; Ledibane, N. R. T.; Claassens, M.M.

    2015-01-01

    Background: South Africa has the second worst tuberculosis-human immunodeficiency virus (TB-HIV) syndemic in the world: in 2011, the TB-HIV co-infection rate was estimated at 65%. Integration of TB and HIV health-care services was implemented to increase antiretroviral treatment (ART) uptake among eligible patients.

  4. Oxidative Imbalance in HIV-1 Infected Patients Treated with Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Antonella Mandas

    2009-01-01

    Full Text Available It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated, and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence. Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants. Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress.

  5. Physical activity and capacity at initiation of antiretroviral treatment in HIV patients in Ethiopia

    DEFF Research Database (Denmark)

    Olsen, Mette Frahm; Kæstel, Pernille; Tesfaye, M;

    2015-01-01

    SUMMARY We described levels of habitual physical activity and physical capacity in HIV patients initiating antiretroviral treatment in Ethiopia and assessed the role of HIV and nutritional indicators on these outcomes. Physical activity energy expenditure (PAEE) and activity levels were measured...

  6. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Kirk, Ole; Reiss, Peter;

    2010-01-01

    OBJECTIVES:: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. DESIGN:: A cohort study including 6843 HIV-positive persons with at...

  7. Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients

    DEFF Research Database (Denmark)

    Lerbaek, Anne; Kristiansen, Thomas B; Katzenstein, Terese L;

    2004-01-01

    The aim of the present study was to explore the treatment effect of tenofovir as implemented in clinical practice. Data are presented on 34 patients. 11 patients had tenofovir added to a stable anti-retroviral treatment (ART) and 23 patients had drugs other than tenofovir. CD4 counts, HIV-RNA lev...

  8. Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Kjær, Jesper;

    2011-01-01

    Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients...

  9. Cancellers - Exploring the Possibility of Receptor Decoy Traps As a Superior Anti-Retroviral Strategy.

    Science.gov (United States)

    Jeremiah, Sundararaj Stanley; Ohba, Kenji; Yamamoto, Naoki

    2016-01-01

    The global Human Immunodeficiency Virus (HIV) pandemic is still spreading due to the lack of ideal anti-retroviral measures and their availability. Till date, all attempts to produce an efficient vaccine have ended with unsatisfactory results. The highly active anti-retroviral therapy (HAART) is the only effective weapon currently available and is widely being used for curtailing the HIV pandemic. However, the HAART is also expected to fail in the near future due to the emergence and dissemination of antiviral resistance. This review sheds light on the reasons for the failure of the conventional anti-viral measures against HIV and the novel anti-retroviral strategies currently being developed. The various principles to be considered for the success of a novel anti-retroviral strategy are elaborately emphasized and an innovative concept is proposed on these lines. The proposed concept intends to use receptor decoy traps (RDT) called cancellers which are erythrocytes expressing the HIV entry receptors on their surface. If successfully developed, the cancellers would be capable of active targeting of the free HIV particles leading to the trapping of the viruses within the canceller, resulting in the neutralization of infectivity of the trapped virus. The possible ways of translating this concept into reality and the probable hurdles that can be encountered in the process are subsequently discussed. Also, the scope of cancellers in therapeutic and/or preventive strategies against HIV infection is envisaged upon their successful development. PMID:25882216

  10. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

    NARCIS (Netherlands)

    Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; 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.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; 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.; Billaud, E.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J.M.; Touraine, J.L.; Cotte, L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Cabié, A.; Gaud, C.; Contant, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Haerry, D.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez De Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; Casabona, J.; Gallois, A.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J.M.; Manzardo, C.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Cifuentes, C.; Dalmau, D.; Jaen, À.; Agustí, C.; Montoliu, A.; Pérez, I.; Gargoulas, Freyra; Blanco, J.L.; Garcia-Alcaide, F.; Martínez, E.; Mallolas, J.; López-Dieguez, M.; García-Goez, J.F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M.C.; Saumoy, M.; Imaz, A.; Tiraboschi, J.M.; Murillo, O.; Bolao, F.; Peña, C.; Cabellos, C.; Masó, M.; Vila, A.; Sala, M.; Cervantes, M.; Jose Amengual, Ma.; Navarro, M.; Penelo, E.; Barrufet, P.; Bejarano, G.; Molina, J.; Guadarrama, M.; Alvaro, M.; Mercadal, J.; Fernandez, Juanse; Ospina, Jesus E.; Muñoz, M.A.; Caro-Murillo, A.M.; Sobrino, P.; Jarrín, I.; Gomez Sirvent, J.L.; Rodríguez, P.; Aleman, M.R.; Alonso, M.M.; Lopez, A.M.; Hernandez, M.I.; Soriano, V.; Labarga, P.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M.E.; Martín, L.; Ramírez, G.; De Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, Rl.; Iribarren, J.A.; Arrizabalaga, J.; Aramburu, M.J.; Camino, X.; Rodrí-guez-Arrondo, F.; Von Wichmann, M.A.; Pascual, L.; Goenaga, M.A.; Gutierrez, F.; Masia, M.; Ramos, J.M.; Padilla, S.; Sanchez-Hellín, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Berenguer, J.; Lopez, J.C.; Miralles, P.; Cosín, J.; Sanchez, M.; Gutierrez, I.; Ramírez, 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.; Cuéllar, S.; De Los Santos, I.; Sanz, J.; Oteo, J.A.; Blanco, J.R.; Ibarra, V.; Metola, L.; Sanz, M.; Pérez-Martínez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M.J.; Irigoyen, C.; Moreno, S.; Antela, A.; Casado, J.L.; Dronda, F.; Moreno, A.; Pérez, M.J.; López, D.; Gutiérrez, C.; Hernández, B.; Pumares, M.; Martí, P.; García, L.; Page, C.; García, F.; Hernández, J.; Peña, A.; Muñoz, L.; Parra, J.; Viciana, P.; Leal, M.; López-Cortés, L.F.; Trastoy, M.; Mata, R.; Justice, A.C.; Fiellin, D.A.; 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.; 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.; Hernán, 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.; Babiker, A.; Brettle, R.; Darbyshire, J.; Gilson, R.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Pillay, D.; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Louisa Gnatiuc, S.L.; Murphy, Brendan; 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, J.A.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Tayal, S.; Short, L.; Roberts, M.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, N.D.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; De Souza, C.B.; Isaksen, A.; McDonald, L.; McLean, K.; Franca, A.; Hawkins, D.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P.J.; Mazhude, C.; Gilson, R.; Johnstone, R.; Fakoya, A.; McHale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Johnson, M.; Rice, P.; Fidler, S.; Mullaney, S.A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey-Puttock, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Tayal, S.; Haynes, J.; Evans, E.; Ong, E.; Das, R.; 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, V.S.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Wilkins, E.; 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.; Roberts, M.; Williams, O.; Luzzi, G.; FitzGerald, M.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Molina, J.M.; Loze, B.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Raffi, F.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Delfraissy, J.F.; Goujard, C.; Ghosn, J.; Rannou, M.T.; Bergmann, J.F.; Badsi, E.; Rami, A.; Diemer, M.; Parrinello, M.; Girard, P.M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Livrozet, J.M.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A.P.; Allègre, T.; Reynes, J.; Baillat, V.; Lemoing, V.; Merle De Boever, C.; Tramoni, C.; Cabié, A.; Sobesky, G.; Abel, S.; Beaujolais, V.; Pialoux, G.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Trepo, C.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Thomas, R.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Gourdon, F.; Rouveix, E.; Morelon, S.; Dupont, C.; Olivier, C.; Lortholary, O.; Dupont, B.; Viard, J.P.; Maignan, A.; Ragnaud, J.M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J.D.; Lascaux, A.S.; Dominguez, S.; Dumont, C.; Aumâitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Salmon, D.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M.C.; Drenou, B.; Beck-Wirth, G.; Beck, C.; Benomar, M.; Katlama, C.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Bentata, M.; Touam, F.; Hoen, B.; Drobacheff, C.; Folzer, A.; Massip, P.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J.M.; Fialaire, P.; Loison, J.; Galanaud, P.; Boué, F.; Bornarel, D.; Verdon, R.; Bazin, C.; Six, M.; Ferret, P.; Weiss, L.; Batisse, D.; Gonzales-Canali, G.; Tisne-Dessus, D.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Herson, S.; Amirat, N.; Simon, A.; Brancion, C.; Cabane, J.; Picard, O.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Choutet, P.; Nau, P.; Bastides, F.; May, T.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; De Truchis, P.; Berthé, H.; Domart, Y.; Merrien, D.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A.M.; Zeng, A.; Fournier, L.; Fuzibet, J.G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Dellamonica, P.; Chaillou, S.; Sabah, M.; 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.; Gastaut, J.A.; Drogoul, M.P.; Poizot Martin, I.; Fabre, G.; Lambert De Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J.L.; Leprêtre, 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.; Caron, F.; Debab, Y.; Tremollieres, F.; Perronne, V.; Lepeu, G.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Galanaud, P.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G.A.; Levy, A.; Delfraissy, J.F.; Goujard, C.; Duracinsky, M.; Le Bras, P.; Ngussan, M.S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Weiss, L.; Buisson, M.; Piketty, C.; Karmochkine, M.; Batisse, D.; Eliaszewitch, M.; Jayle, D.; Tisne-Dessus, D.; Kazatchkine, M.; Leport, C.; Colasante, U.; Jadand, C.; Jestin, C.; Duval, X.; Nouaouia, W.; Boucherit, S.; Vilde, J.L.; Girard, P.M.; Bollens, D.; Binet, D.; Diallo, B.; Meyohas, M.C.; Fonquernie, L.; Lagneau, J.L.; Salmon, D.; Guillevin, L.; Tahi, T.; Launay, O.; Pietrie, M.P.; Sicard, D.; Stieltjes, N.; Michot, J.; Sobel, A.; Levy, Y.; Bourdillon, F.; Lascaux, A.S.; Lelievre, J.D.; Dumont, C.; Dupont, B.; Obenga, G.; Viard, J.P.; Maignan, A.; Vittecoq, D.; Escaut, L.; Bolliot, C.; Bricaire, F.; Katlama, C.; Schneider, L.; Herson, S.; Simon, A.; Iguertsira, M.; Stein, A.; Tomei, C.; Ravaux, I.; Dhiver, C.; Tissot Dupont, H.; Vallon, A.; Gallais, J.; Gallais, H.; Gastaut, J.A.; Drogoul, M.P.; Fabre, G.; Dellamonica, P.; Durant, J.; Mondain, V.; Perbost, I.; Cassuto, J.P.; Karsenti, J.M.; Venti, H.; Fuzibet, J.G.; Rosenthal, E.; Ceppi, C.; Quaranta, M.; Krivitsky, J.A.; Bentata, M.; Bouchaud, O.; Honore, P.; Sereni, D.; Lascoux, C.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Pérez-Hoyos, S.; Del Amo, J.; Alvarez, D.; Monge, S.; Muga, R.; Sanvisens, A.; Clotet, B.; Tor, J.; Bolao, F.; Rivas, I.; Vallecillo, G.; Del Romero, J.; Raposo, P.; Rodríguez, C.; Vera, M.; Hurtado, I.; Belda, J.; Fernandez, E.; Alastrue, I.; Santos, C.; Tasa, T.; Juan, A.; Trullen, J.; Garcia De Olalla, P.; Cayla, J.; Masdeu, E.; Knobel, H.; Mirò, J.M.; Sambeat, M.A.; Guerrero, R.; Rivera, E.; Guerrero, R.; Marco, A.; Quintana, M.; Gonzalez, C.; Castilla, J.; Guevara, M.; De Mendoza, C.; Zahonero, N.; Ortíz, M.; Paraskevis, D.; Touloumi, G.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; Antoniadou, A.; Papadopoulos, A.; Petrikkos, G.; Daikos, G.; Psichogiou, M.; Gargalianos-Kakolyris, P.; Xylomenos, G.; Katsarou, O.; Kouramba, A.; Ioannidou, P.; Kordossis, T.; Kontos, A.; Lazanas, M.; Chini, M.; Tsogas, N.; Panos, G.; Paparizos, V.; Leuow, K.; Kourkounti, S.; Sambatakou, H.; Mariolis, I.; Skoutelis, A.; Papastamopoulos, V.; Baraboutis, I.

    2014-01-01

    Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacteri

  11. The occurrence of anti-retroviral compounds used for HIV treatment in South African surface water

    International Nuclear Information System (INIS)

    The study and quantification of personal care products, such as pharmaceuticals, in surface water has become popular in recent years; yet very little description of these compounds’ presence in South African surface water exists in the literature. Antiretrovirals (ARVs), used to treat human immunodeficiency virus (HIV) are rarely considered within this field. A new method for the simultaneous quantification of 12 antiretroviral compounds in surface water using the standard addition method is described. Water samples were concentrated by a generic automated solid phase extraction method and analysed by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Substantial matrix effect was encountered in the samples with an average method detection limit of 90.4 ng/L. This is the first reported countrywide survey of South African surface water for the quantification of these compounds with average concentrations ranging between 26.5 and 430 ng/L. - Highlights: • An LC-MS/MS method for the detection of 12 antiretroviral drugs was developed. • The compounds were detected in South African surface water for the first time. • Targets occurred in the low to mid ng/L range. • Nevirapine occurred ubiquitously across all the samples tested. • Matrix effect was corrected for using a modified standard addition method. - This work represents the first quantitative description of anti-retrovirals, as a group, in surface water using a modified standard addition method and UHPLC-MS/MS

  12. Assessing treatment motivation among patients receiving antiretroviral therapy: A multidimensional approach

    OpenAIRE

    Houston, Eric; McKirnan, David J.; Cervone, Daniel; Matthew S. Johnson; Sandfort, Theo G. M.

    2011-01-01

    Using multidimensional scaling analysis (MDS), this study examined how patient conceptualisations of treatment motivation compare with theoretically-based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n = 39) rated for similarity all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach, and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrin...

  13. Anti-Toxoplasma Activities of Antiretroviral Drugs and Interactions with Pyrimethamine and Sulfadiazine In Vitro

    OpenAIRE

    Derouin, Francis; Santillana-Hayat, Maud

    2000-01-01

    The anti-Toxoplasma activities of nine antiretroviral drugs were examined in vitro. Nucleoside analogs had no effect on parasite growth, whereas ritonavir and nelfinavir were inhibitory for Toxoplasma, with 50% inhibitory concentrations of 5.4 and 4.0 μg/ml, respectively. None of the antiviral drugs affected the anti-Toxoplasma activity of pyrimethamine or sulfadiazine.

  14. An investigation into frequency and reasons why patients switch antiretroviral therapy and which antiretrovirals are commonly implicated in toxicity

    Directory of Open Access Journals (Sweden)

    Boyle A

    2012-11-01

    Full Text Available Purpose of the study Previous investigation into antiretroviral (ARV therapy switches in our HIV cohort suggested an annual switch rate of 20% in 2006 with 60% of switches being secondary to toxicity [1]. The purpose of this study was to investigate whether this switch rate has changed in recent years, determine reasons why patients change regimens, and identify which ARVs are most likely to be switched for toxicity concerns. Methods The electronic patient database was reviewed to identify all patients within our HIV cohort who switched ARV therapy between 1st December 2009 and 31st May 2011. Details of which ARVs were switched and the reasons why were recorded. Any switches due to toxicity were investigated further to identify the actual or perceived adverse effect. Summary of results Nine hundred and twenty-three regimens were switched over 18 months affecting 12% (n = 722 of patients on treatment during this time. The most common reason for switching medication was due to toxicity, occurring in 452 (49% cases. Other reasons included simplification (15%, clinical trials (8%, virological failure (8% and drug interactions (4%. The remaining 16% switched for various reasons including pregnancy and co-morbidities. Of 452 switches for toxicity (or perceived toxicity, 122 (27% were due to CNS side effects (89 out of a total of 122 were related to efavirenz, 64 (14% gastrointestinal disturbances (38/64 related to protease inhibitors, 54 (12% actual/perceived cardiovascular risk (21/54 related to abacavir and 21/54 related to saquinavir, 54 (12% hepatotoxicity (21/54 related to atazanavir and 14/54 related to efavirenz, 42 (9% metabolic concerns (24/42 related to protease inhibitors and 38 (8% renal toxicity (28/38 related to tenofovir. Other toxicities accounted for 78 (18% switches. An observed toxicity switch rate (OTSR per 1000 patient years (95% CI was calculated for each ARV. Conclusions 12% of patients switched therapy in 18 months, predicting

  15. 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

    2016-05-01

    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. PMID:26666292

  16. Predicted savings to the UK National Health Service from switching to generic antiretrovirals, 2014–2018

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    Andrew Hill

    2014-11-01

    Full Text Available Introduction: In other disease areas, generic drugs are normally used after patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have already expired. Patents will expire for abacavir in late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single-tablet regimens do not expire until after 2026. Methods: The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database. Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 – all patients use single-tablet regimens and patented versions of drugs; prices remain stable over time; 2 – all people switch from patented to generic drugs when available, after patent expiry (dates shown above. Results: There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018 (in line with previous rises. The most widely used antiretrovirals in the CHIC cohort were tenofovir (TDF (75%, emtricitabine (FTC (69%, efavirenz (EFV (39%, lamivudine (3TC (23%, abacavir (ABC (18%, darunavir (DRV (21% and atazanavir (ATV (16%. The predicted annual UK cost of generic ABC/3TC/EFV (three generic tablets once daily was £1018 per person-year. Costs of patented single-tablet regimens ranged from £5000 to £7500 per person-year. Assuming continued use of patented antiretrovirals in the UK, the predicted total national costs of antiretroviral treatment were predicted to rise from £425 million in 2014 to £459 m in 2015, £495 m in 2016, £536 m in 2017 and £578 m in 2018. With a 100% switch to generics, total predicted costs were £337 m in 2014, £364 m in 2015, £382 m in 2016, £144 m in 2017 and £169 m in 2018. The total

  17. Gender differences in clinical, immunological, and virological outcomes in highly active antiretroviral-treated HIV–HCV coinfected patients

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    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

  18. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

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    Andreu-Crespo À

    2015-08-01

    Full Text Available Àngels Andreu-Crespo,1,* Josep M Llibre,2,3,* Glòria Cardona-Peitx,1 Ferran Sala-Piñol,1 Bonaventura Clotet,2,4 Xavier Bonafont-Pujol1 1Pharmacy Department, 2HIV Unit and “Lluita contra la SIDA” Foundation, University Hospital Germans Trias i Pujol, Badalona, 3Universitat Autònoma de Barcelona, 4Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC, Vic, Barcelona, Spain *These authors contributed equally to the work Abstract: While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar, should minimize the treatment expenditures paid by national health budgets. Keywords: antiretroviral treatment, cost efficacy, drug packaging, treatment change

  19. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    Science.gov (United States)

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation. PMID:26862469

  20. Treatment Adherence and Outcomes of Antiretroviral Agents in HIV Positive Patients

    International Nuclear Information System (INIS)

    Objective: To describe the treatment outcomes in terms of adherence, outcomes and side effects of antiretroviral (ARV) agents. Study Design: An observational study. Place and Duration of Study: Teaching Hospital of Khyber Medical University, Institute of Medical Sciences, Kohat, from February 2007 to December 2012. Methodology: Human Immunodeficiency Virus (HIV) positive patients, taking 1st line ARV agents for at least 6 months were included. Adherence was calculated by self report on asking the number of doses missed in last 30 days. ARVs were provided on monthly basis. Adherence data was noted over a period of 6 months. ARVs outcomes were recorded in the form of adherence, CD4 count, functional status of the patient, change in weight, further transmission of the disease, number of hospital admissions and deaths. Adverse Drug Reactions (ARDs) to ARVs were assessed clinically and by laboratory markers. Mean and standard deviation were calculated for numerical variables while frequencies and percentages were calculated for categorical variables. Results: Total number of patients included in this study were 107. Out of them, 66.4% were males and 33.6% were females. The mean age was 39.9 +- 13.80 years. Patients taking AZT/3TC/NVP, AZT/3TC/EFZ, D4T/3TC/NVP, D4T/3TC/EFZ, TNF/3TC/NVP or EFZ were 49.5%, 22.4%, 10.3%, 4.7% and 13% respectively. Most adverse affects were observed in 10 days to 90 days of initiation of therapy. Rash was observed in 71 (66.4%) patients, anaemia in 4 (3.7%) patients while only one patient (0.93%) had nausea / vomiting. Thirty (28%) patients reported no side effects. Out of 107 patients, 98 (91.5%) were alive whereas 9 (8.4%) died at the end of the study period. Twelve patients had one hospital admission (11.21%) whereas 9 (8.4%) patients had two admissions during the study period. The first mean CD4 was 325.27 cells /mcL whereas mean last CD4 count was 389.86 cells/mcL. Conclusion: ARVs have very satisfactory outcomes in HIV/AIDS patients

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

    Science.gov (United States)

    Lee, Sulggi A.; Bacchetti, Peter; Chomont, Nicolas; Fromentin, Remi; Lewin, Sharon R.; O’Doherty, Una; Palmer, Sarah; Richman, Douglas D.; Siliciano, Janet D.; Yukl, Steven A.; Deeks, Steven G.; Burbelo, Peter D.

    2016-01-01

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

  2. Community-Based Accompaniment Mitigates Predictors of Negative Outcomes for Adults on Antiretroviral Therapy in Rural Rwanda.

    Science.gov (United States)

    Gupta, Neil; Munyaburanga, Christian; Mutagoma, Mwumvaneza; Niyigena, John W; Kayigamba, Felix; Franke, Molly F; Hedt-Gauthier, Bethany

    2016-05-01

    Clinical, socioeconomic, and access barriers remain a critical problem to antiretroviral (ART) programs in sub-Saharan Africa. Community-based accompaniment (CBA), including daily home visits and psychosocial and socioeconomic support, has been associated with improved patient outcomes at 1 year. We conducted a prospective observational cohort study of 578 HIV-infected adults initiating ART in 2007-2008 with or without CBA in rural Rwanda. Among patients without CBA, those with advanced HIV disease, low CD4 cell counts, lower social support, and transport costs had significantly higher odds of negative outcomes at 1 year; amongst patients who received CBA, only those with low CD4 cell counts had significantly higher odds of negative outcomes at 1 year. CBA also significantly mitigated the effect of transport costs and inaccessibility of services on the likelihood of negative outcome. CBA may be one approach to mitigating known risk factors for negative outcomes for patients on ART in resource-poor settings. PMID:26346334

  3. CD4 changes among virologically suppressed patients on antiretroviral therapy: a systematic review and meta-analysis

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    Nathan Ford

    2015-08-01

    Full Text Available Introduction: The effectiveness of antiretroviral therapy (ART is assessed by measuring CD4 cell counts and viral load. Recent studies have questioned the added value of routine CD4 cell count measures in patients who are virologically suppressed. Methods: We systematically searched three databases and two conference sites up to 31 October 2014 for studies reporting CD4 changes among patients who were on ART and virologically suppressed. No geographic, language or age restrictions were applied. Results and discussion: We identified 12 published and 1 unpublished study reporting CD4 changes among 20,297 virologically suppressed patients. The pooled proportion of patients who experienced an unexplained, confirmed CD4 decline was 0.4% (95% CI 0.2–0.6%. Results were not influenced by duration of follow-up, age, study design or region of economic development. No studies described clinical adverse events among virologically suppressed patients who experienced CD4 declines. Conclusions: The findings of this review support reducing or stopping routine CD4 monitoring for patients who are immunologically stable on ART in settings where routine viral load monitoring is provided.

  4. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    Science.gov (United States)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  5. Current trends in highly active anti-retroviral therapy in an anti-retroviral therapy centre attached to a remote government medical college of Maharashtra, India: a retrospective study

    OpenAIRE

    Pravin S. Rathod; Praveenkumar T Patil; Rekha P. Lohar; A.W. Patil

    2016-01-01

    Background: Highly active anti-retroviral therapy (HAART) became the keystone of national AIDS program. There is lack of awareness and inadequate training about drug safety monitoring among health care professionals in India. Hence, the present study was carried out to study current trends in HAART and pattern of associated adverse drug reactions. Methods: A retrospective observational study was conducted at an anti-retroviral therapy (ART) Centre. A total of 151 HIV/AIDS Patients (old and...

  6. Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial.

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    Sydney Rosen

    2016-05-01

    Full Text Available High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.RapIT (Rapid Initiation of Treatment was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC and a hospital-based HIV clinic. Adult (≥18 y old, non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm" received a point-of-care (POC CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV dispensing. Patients in the standard-initiation arm of the study ("standard arm" followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing. Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition

  7. Initiating Antiretroviral Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial

    Science.gov (United States)

    Rosen, Sydney; Maskew, Mhairi; Fox, Matthew P.; Nyoni, Cynthia; Mongwenyana, Constance; Sanne, Ian; Sauls, Celeste; Long, Lawrence

    2016-01-01

    Background High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. Methods and Findings RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (“rapid arm”) received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (“standard arm”) followed standard clinic procedures (three to five additional clinic visits over 2–4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis

  8. 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 strategies....... METHODS: A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional...... demographic variables. Baseline was defined as the date of starting new antiretrovirals. RESULTS: Four hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment...

  9. Rinossinusites em crianças infectadas pelo HIV sob terapia anti-retroviral Rhinosinusitis in HIV-infected children undergoing antiretroviral therapy

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    Carlos Diógenes Pinheiro Neto

    2009-02-01

    Full Text Available A associação dos inibidores de protease (IP à terapia anti-retroviral provocou mudanças importantes na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto desta associação na prevalência de rinossinusite (RS e na contagem sérica de linfócitos CD4 em crianças infectadas pelo HIV. CASUÍSTICA E MÉTODOS: A forma de estudo foi cross-sectional com 471 crianças infectadas pelo HIV. Em 1996, inibidores de protease foram liberados para terapia anti-retroviral. Desta forma, dois grupos de crianças foram formados: as que não fizeram uso de IP e as que fizeram uso desta droga após 1996. A prevalência de RS e a contagem sérica de linfócitos CD4 foram comparadas entre estes grupos. RESULTADOS: 14,4% das crianças infectadas pelo HIV apresentaram RS. A RS crônica foi mais prevalente que a RS aguda em ambos os grupos. Crianças menores de 6 anos tratadas com a associação de IP apresentaram maior prevalência de RS aguda. A associação de IP esteve associada à maior contagem de linfócitos CD4 séricos com menor prevalência de RS crônica. CONCLUSÕES: A terapia com IP esteve associada ao aumento na contagem de linfócitos CD4. Crianças abaixo dos 6 anos em uso de IP apresentaram menor tendência à cronificação da doença.The association of protease inhibitors (PI to antiretroviral therapy has generated sensible changes in morbidity and mortality of HIV-infected patients. AIM: Aims at evaluating the impact of this association on the prevalence of rhinosinusitis (RS and CD4+ lymphocyte count in HIV-infected children. METHODS: Retrospective cross-sectional study of the medical charts of 471 HIV-infected children. In 1996, protease inhibitors were approved for use as an association drug in antiretroviral therapy. Children were divided into two groups: one which did not receive PI and another which received PI after 1996. The prevalence of RS and CD4+ lymphocyte counts were compared between these groups

  10. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naive to Antiretroviral Therapy: A Pilot Randomized Trial.

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    Sergio Serrano-Villar

    2016-01-01

    Full Text Available Whether initiation of antiretroviral therapy (ART regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6, lipoteichoic acid (LTA, soluble CD14 (sCD14 and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively, with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease

  11. Adherence to antiretroviral therapy and its determinants in AIDS patients: review article

    Directory of Open Access Journals (Sweden)

    Hajiabdolbaghi M

    2008-10-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} There are limited published investigations about adherence to antiretroviral and its determinants. Many determinants influence on adherence to therapy. The effects of some determinants on adherence are controversial. More studies are needed to be fulfilled about adherence and its determinants to compile strategies. Key to the success of antiretroviral therapies is the ability and willingness of HIV-positive individuals to adhere to antiretroviral regimens. There are different definitions for full adherence. In the most studies, adherence is defined as taking ≥95% of prescribed medication. Adherence rate needs to be >95% to prevent virologic failure and for complete supper-ssion. The consequences of poor adherence include not only diminished benefits for the patient, but also the public health threat of the emergence of multidrug-resistant viruses, as these resistant strains can then be transmitted from a patient to their contacts. Evaluating adherence has proven to be difficult and there is no gold standard for evaluating adherence to medication. Adherence is assessed in various ways. The most studies evaluate adherence to treatment by using patient's self report and the pill count method but these are methods

  12. Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

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    Karolin Hijazi

    Full Text Available 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

  13. Short term adherence tool predicts failure on second line protease inhibitor-based antiretroviral therapy: an observational cohort study

    OpenAIRE

    Court, Richard; Leisegang, Rory; Stewart, Annemie; Sunpath, Henry; Murphy, Richard; Winternheimer, Philip; Ally, Mashuda; Maartens, Gary

    2014-01-01

    Background Most patients who experience virologic failure (VF) on second line antiretroviral therapy (ART) in low-middle income countries fail due to poor adherence rather than antiretroviral resistance. A simple adherence tool designed to detect VF would conserve resources by rationally limiting need for viral load (VL) testing and, in those countries with access to third line ART, the need for resistance testing. Methods We conducted an observational cohort study of patients who initiated s...

  14. Antiretroviral Strategies to Prevent Mother-to-Child Transmission of HIV: Striking a Balance between Efficacy, Feasibility, and Resistance

    OpenAIRE

    McIntyre, James A; Hopley, Mark; Moodley, Daya; Eklund, Marie; Gray, Glenda E.; Hall, David B.; Robinson, Patrick; Mayers, Douglas; Martinson, Neil A

    2009-01-01

    Editors' Summary Background Currently, about 33 million people are infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV can be treated with combination antiretroviral therapy (ART), commonly three individual antiretroviral drugs that together efficiently suppress the replication of the virus. HIV infection of a child by an HIV-positive mother during pregnancy, labor, delivery, or breastfeeding is called mother-to-child transmission (MTCT). In 2007, an estimated 420,000...

  15. Prices of second-line antiretroviral treatment for middle-income countries inside versus outside sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Bryony Simmons

    2014-11-01

    Full Text Available Introduction: Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. Methods: HIV drug prices used in national programmes (2010–2014 were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Results: Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (p<0.001, adjusted for year of purchase (see Table 1. For example, the median (interquartile range price of darunavir from Janssen was $732 (IQR $732-806 per person-year in sub-Saharan Africa versus $4689 (IQR $4075-5717 in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Conclusions: Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74–541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access.

  16. EFFECT OF IRIS DEVELOPMENT ON SURVIVAL IN HIV-TB PATIENTS ON ANTIRETROVIRAL THERAPY AMONG NORTH INDIAN POPULATION

    OpenAIRE

    Priyanka Gupta; Anil Kumar Tripathi; Amita Jain; Rajendra Prasad; Kaleshwar Prasad Singh; Arvind Kumar Vaish; Rajendra Prasad Misra

    2012-01-01

    Background: The survival of people with HIV-associated TB has not been extensively studied. The objective of this present study was to explore the association of Immune reconstitution inflammatory syndrome (IRIS) development and mortality in HIV patients initiated on antiretroviral therapy (ART). Methods: This was a prospective cohort study of 400 HIV positive patients who initiated antiretroviral therapy and followed up for one year. Baseline clinical and immunological parameters were assess...

  17. Alcohol use and incarceration adversely affect HIV-1 RNA suppression among injection drug users starting antiretroviral therapy

    OpenAIRE

    Palepu, Anita; Tyndall, Mark W.; Li, Kathy; Yip, Benita; O’Shaughnessy, Michael V.; Schechter, Martin T.; Montaner, Julio S.G.; Hogg, Robert S.

    2003-01-01

    We conducted this study among HIV-infected injection drug users to determine the effect of self-reported alcohol use and prior incarceration at the time of initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We examined the demographics, recent incarceration history, and drug and alcohol use history from the Vancouver Injection Drug User Study (VIDUS) questionnaire closest to the date of initiating antiretroviral therapy. We linked these data to the HIV/AIDS Drug Treatment ...

  18. Self-Initiation of Antiretroviral Therapy in the Developing World: the Involvement of Private Pharmacies in an HIV Program.

    OpenAIRE

    2012-01-01

    Background Self-initiation to antiretroviral treatment (ART) exposes the patient to the risk of drug toxicity, poor adherence to treatment, and escalates the development of drug resistance. Objectives To determine the sources of antiretroviral (ARV) drugs by unregistered human immunodeficiency virus (HIV)-infected patients and the extent of ARV self-medication. Methods Simulated clients were used to investigate availability and ARV dispensing practice in the private pharmacies in Dar Es Salaa...

  19. Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study

    OpenAIRE

    Scott, Callie A.; Iyer, Hari S.; McCoy, Kelly; Moyo, Crispin; Long, Lawrence; Bruce A. Larson; Rosen, Sydney

    2014-01-01

    Background Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia. Methods Data on resource utilization (antiretroviral [A...

  20. Resistance to antiretroviral drugs in treated and drug-naive patients in the Democratic Republic of Congo

    OpenAIRE

    Muwonga, J; Edidi, S.; Butel, Christelle; Vidal, Nicole; Monleau, Marjorie; Okenge, A; Mandjo, J. L.; Mukumbi, H.; Muyembe, J. J.; Mbayo, F.; Nzongola, D. K.; Delaporte, Eric; Boillot, F.; Peeters, Martine

    2011-01-01

    Background: We studied virological outcome and drug resistance in patients on antiretroviral therapy (ART) in health care centers in the Democratic Republic of Congo and looked for the presence of drug resistance in antiretroviral-naive patients attending the same clinics. Methods: In 2008, we conducted a cross-sectional survey among patients on ART for >= 12 months in 4 major cities [Kinshasa (n = 289), Matadi (n = 198), Lubumbashi (n = 77), and Mbuji-Mayi (n = 103)]. Genotypic drug resistan...

  1. Timing Is Everything: Antiretroviral Non-adherence is Associated with Impairment in Time-based Prospective Memory

    OpenAIRE

    Woods, Steven Paul; Dawson, Matthew S.; Weber, Erica; Gibson, Sarah; Grant, Igor; Atkinson, J. Hampton

    2009-01-01

    Non-adherence to combination antiretroviral therapies (cART) is highly prevalent and significantly increases the risk of adverse HIV disease outcomes. The current study evaluated the hypothesis that prospective memory – a dissociable aspect of episodic memory describing the ability to execute a future intention – plays an important role in successful cART adherence. Seventy-nine individuals with HIV infection who were prescribed at least one antiretroviral medication underwent a comprehensive...

  2. Hypertriglyceridemia, Metabolic Syndrome, and Cardiovascular Disease in HIV-Infected Patients: Effects of Antiretroviral Therapy and Adipose Tissue Distribution

    OpenAIRE

    van Wijk, Jeroen P. H.; Manuel Castro Cabezas

    2011-01-01

    The use of combination antiretroviral therapy (CART) in HIV-infected patients has resulted in a dramatic decline in AIDS-related mortality. However, mortality due to non-AIDS conditions, particularly cardiovascular disease (CVD) seems to increase in this population. CART has been associated with several metabolic risk factors, including insulin resistance, low HDL-cholesterol, hypertriglyceridemia and postprandial hyperlipidemia. In addition, HIV itself, as well as specific antiretroviral age...

  3. Clinician perceptions and patient experiences of antiretroviral treatment integration in primary health care clinics, Tshwane, South Africa

    OpenAIRE

    Maphuthego D. Mathibe; Stephen J.H. Hendricks; Anne-Marie Bergh

    2015-01-01

    Background: Primary Health Care (PHC) clinicians and patients are major role players in the South African antiretroviral treatment programme. Understanding their perceptions and experiences of integrated care and the management of people living with HIV and AIDS in PHC facilities is necessary for successful implementation and sustainability of integration.Objective: This study explored clinician perceptions and patient experiences of integration of antiretroviral treatment in PHC clinics.Meth...

  4. Building capacity for antiretroviral delivery in South Africa: A qualitative evaluation of the PALSA PLUS nurse training programme

    OpenAIRE

    English R; Mayers P; Fairall L; Lewin S.; Stein J; Bheekie A; Bateman E; Zwarenstein M

    2008-01-01

    Abstract Background South Africa recently launched a national antiretroviral treatment programme. This has created an urgent need for nurse-training in antiretroviral treatment (ART) delivery. The PALSA PLUS programme provides guidelines and training for primary health care (PHC) nurses in the management of adult lung diseases and HIV/AIDS, including ART. A process evaluation was undertaken to document the training, explore perceptions regarding the value of the training, and compare the PALS...

  5. Perception of Antiretroviral Generic Medicines: One-Day Survey of HIV-Infected Patients and Their Physicians in France

    OpenAIRE

    Jacomet, Christine; Allavena, Clotilde; Peyrol, Fleur; Pereira, Bruno; Joubert, Laurence Morand; Bagheri, Haleh; Cotte, Laurent; Garaffo, Rodolphe; Gerbaud, Laurent; Dellamonica, Pierre

    2015-01-01

    Background 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 Methods and Findings 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 comple...

  6. Longitudinal comparison between plasma and seminal HIV-1 viral loads during antiretroviral treatment Comparação longitudinal entre cargas virais seminais e plasmáticas do HIV-1 durante terapia anti-retroviral

    Directory of Open Access Journals (Sweden)

    Lauro Ferreira da Silva Pinto Neto

    2003-12-01

    Full Text Available This study was designed to investigate the impact of anti-retroviral therapy on both plasma and seminal HIV-1 viral loads and the correlation between viral loads in these compartments after treatment. Viral load, CD4+ and CD8+ T-cell counts were evaluated in paired plasma and semen samples from 36 antiretroviral therapy-naïve patients at baseline and on days 45, 90, and 180 of treatment. Slopes for blood and seminal viral loads in all treated patients were similar (p = 0.21. Median HIV-1 RNA titers in plasma and semen at baseline were 4.95 log10 and 4.48 log10 copies/ml, respectively. After 180 days of therapy, the median viral load declined to 3.15 log10 copies/ml (plasma and 3.2 log10 copies/ml (semen. At this timepoint 22 patients presented HIV-1 viral load below 400 copies/ml in either plasma or semen, but only 9 had viral loads below 400 copies/ml in both compartments.Este estudo foi desenhado para investigar o impacto do tratamento com anti-retrovirais na evolução das cargas virais plasmáticas e seminais do HIV-1. A carga viral do HIV-1 e a contagem de linfócitos T CD4+ e CD8+ foi determinada em amostras pareadas de sangue e sêmen de 36 pacientes virgem de tratamento nos dias 0, 45, 90 e 180 após o início da terapia. As curvas de declínio das cargas virais plasmática e seminal foram semelhantes (p= 0.21. As medianas da carga viral plasmática e seminal no pré-tratamento (dia 0 foram 4.95 e 4.48 log10 cópias/ml, respectivamente. Seis meses após o início da terapia, a mediana da carga viral plasmática era 3.15 log10 cópias/ml e a seminal 3.2 log10 cópias/ml. Neste mesmo periodo, 22 pacientes apresentavam carga viral abaixo de 400 cópias/ml no plasma e/ou sêmen, enquanto apenas 9 pacientes apresentavam carga viral abaixo do limite de detecção nos dois compartimentos.

  7. Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

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    Niklaus Daniel Labhardt

    2013-11-01

    Full Text Available Introduction: Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs to scale up the provision of antiretroviral therapy (ART. We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods: The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results: Of 3747 patients, 2042 (54.5% started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81 and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001. These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR: 0.89, 95% confidence interval (CI: 0.73–1.09 and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20–1.96. The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51–0.93. Conclusions: In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities

  8. Clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy.

    Science.gov (United States)

    So-Ngern, Apichot; Montakantikul, Preecha; Manosuthi, Weerawat

    2014-09-01

    We conducted a cross sectional study of the outpatient medical records of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in 2011 to determine the incidence of clinically significant drug interactions (CSDI). The severities of the CSDI were graded following the Micromedex" 2.0 database and the Department of Health and Human Services (DHHS) 2012 HIV treatment guidelines. Three hundred thirty-five patients (34%) had 554 episodes of CSDI. Of which 337 episodes (61%), 163 episodes (29%) and 54 episodes (10%) had grades 2, 3 and 4 severity CSDI, respectively. The CSDI were caused by protease inhibitor (PI)-based drug regimens in 79%, by efavirenz-based regimens in 34% and by nevirapine-based regimens in 10% (pgemfibrozil (n=24) and didanosine with allopurinol (n=2). The three most common grade 3 CSDI were: a PI with a statin drug except simvastatin (n=56), fenofibrate with a statin drug (n=28) and amlodipine with simvastatin (n=14). On multivariate analysis, risk factors associated with CSDI were: receiving a PI-based regimen (OR 14.44; 95% CI: 9.10-22.88), having dyslipidemia (OR 3.94; 95% CI: 1.89-8.21), having >5 items prescribed at a time (OR 1.80; 95% CI: 1.23-2.63), seeing a doctor >4 times a year (OR 1.72; 95% CI: 1.20-2.46), having hypertension (OR 0.60; 95% CI: 0.37-0.98), having a duration of receiving ART of >5 years (OR 0.46; 95% CI: 0.28-0.77) and having a CD4 count of >200 cells/mm3 (OR 0.46; 95%CI: 0.26-0.84). CSDI were common among HIV-infected patients receiving ARV in our outpatient clinic. Patients having a low CD, count, having dyslipidemia, receiving PI-based ART, having a frequent number of visits per year and having a large number of items prescribed at each visit had a greater chance of a CSDI. PMID:25417503

  9. Adherence and retention on antiretroviral therapy in a public-private partnership program in Nigeria

    Directory of Open Access Journals (Sweden)

    K Torpey

    2012-11-01

    Full Text Available Initiation of HIV-positive patients on antiretroviral therapy (ART in Nigeria was restricted to secondary and tertiary level hospitals due to weak health systems in primary health centres (PHCs. Shell Petroleum Development Company (SDPC Nigeria and FHI 360 using a systems strengthening approach, piloted ART enrolment in a PHC in south-eastern Nigeria. This study sought to evaluate patients’ adherence and mortality on ART, and associated risk factors. We reviewed clinic records of adult patients initiating ART between January 2007 and December 2009. Adherence was calculated as the number of days of medication dispensed as a percentage of total number of days evaluated. Outcome measures were probability of being alive and retained in care at 12 and 24 months on ART. Competing risks regression models were used to assess potential predictors associated with mortality. Total of 196 patients (64.8% males were initiated on ART. Patients’ median age was 35 years (IQR 30–44; median CD4 at initiation was 132 cells/mm3 (IQR 82–212, Patients in WHO stage III and IV constituted 73 (37.6% and 83 (42.8% respectively. Majority (108 [55.1%] of patients had adherence rates >95%. Adherence levels ranged: 70–85%, 50–65% and <50% in 29 (14.8%, 30 (15.3% and 29 (14.8% of patients respectively. Nucleoside backbone use were AZT/3TC (69.4% d4T/3TC (28.6% and TDF/FTC (2%. At 12 months of follow up, 80.6% (158 were alive and on ART, mortality accounted for 12.8% (25, 11 (5.6% were LTFU and 2 (1.1% transferred out. At 24 months on ART survival decreased to 64.3% (126, 20.4% (40 died, 9.2% (18 were LTFU and 12 (6.1% transferred out. Competing risks regression models revealed that patients’ factors significantly associated with mortality include: bedridden patients (HR=3.6 [95% CI: 1.11–11.45], p=0.03, referent: working, <50% adherence levels (HR=27.7 [95% CI: 8.55–89.47], p<0.0001, referent: >95% adherence level. In conclusion, majority of attrition was

  10. Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa.

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    Katharina Kranzer

    Full Text Available BACKGROUND: Antiretroviral therapy (ART has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART. METHODOLOGY: Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885 was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103 testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis. FINDINGS: Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1% and individuals testing on their own initiative (53.5% the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period. CONCLUSION: Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.

  11. Anti-retroviral strategies for AIDS and related diseases

    OpenAIRE

    Wainberg, Mark A.; Dascal, Andre; Mendelson, Jack

    1991-01-01

    The replication cycle of human immunodeficiency virus type 1 (HIV-1) and other retroviruses consists of four stages: attachment of the virus to specific receptors on the cell surface; uncoating of the viral nucleic acid and conversion to DNA; production of viral RNA and proteins; and assembly and liberation of progeny virus from the cell. Each of these steps represents a potential target for antiviral chemotherapy. Combinations of drugs which act against different steps in the viral replicati...

  12. Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Carlos J Montoya

    2007-06-01

    Full Text Available Given that highly active antiretroviral therapy (HAART has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40 against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

  13. Choosing Initial Antiretroviral Therapy: Current Recommendations for Initial Therapy and Newer or Investigational Agents.

    Science.gov (United States)

    Gulick, Roy M

    2015-01-01

    There is general consistency among US and European guidelines regarding the initiation of antiretroviral therapy for HIV-infected individuals. Recent and ongoing trials comparing regimens may lead to reevaluation of initial treatment choices. The choice of antiretroviral regimen will also likely be affected by development, evaluation, and availability of newer drugs. This article reviews currently recommended regimens and characteristics of selected current investigational drugs, including the nucleotide analogue reverse transcriptase inhibitor tenofovir alafenamide, the nonnucleoside reverse transcriptase inhibitor doravirine, the integrase strand transfer inhibitor cabotegravir, the HIV entry inhibitor BMS-663068, and the HIV maturation inhibitor BMS-955176. This article summarizes a presentation by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in March 2015 and September 2015. PMID:26713502

  14. Antiretroviral regimen and suboptimal medication adherence are associated with low-level human immunodeficiency virus viremia.

    Science.gov (United States)

    Konstantopoulos, Christina; Ribaudo, Heather; Ragland, Kathleen; Bangsberg, David R; Li, Jonathan Z

    2015-01-01

    Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification. PMID:25884007

  15. Triple Active Antiretroviral Regimen Including Enfuvirtide Via the Biojector is Effective and Safe

    Directory of Open Access Journals (Sweden)

    Mona Loutfy

    2007-01-01

    Full Text Available For full HIV virological suppression, three fully active antiretroviral agents are required. New drug classes should be included to ensure that agents are fully active. The addition of enfuvirtide and efavirenz to the present patient’s new antiretroviral regimen ensured that two fully active agents were in use in the setting of a moderate degree of nucleoside resistance and a high level of protease resistance, and where non-nucleoside reverse transcriptase inhibitors were still fully active. Both viral load and CD4 count responded favourably to this regimen. The patient received support from physicians and clinic staff in the introduction and use of enfuvirtide. To reduce injection site reactions, a needle-free injection system (Biojector proved effective.

  16. Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias;

    2009-01-01

    combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting......), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard...... ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non...

  17. Improving China's antiretroviral treatment program: assessing current and future performance using the principals of ethics

    Institute of Scientific and Technical Information of China (English)

    YIN Wen-yuan; ZHANG Fu-jie; Naomi Juniper; WU Zun-you

    2009-01-01

    @@ The global commitment to providing antiretroviral therapy (ART) to people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in low-income countries has raised hope that the increasing momentum in the fight against the worldwide HIV/AIDS pandemic will be sufficient to control it. However, improved availability of subsidized antiretroviral (ARV) treatments in low-income countries raises complex ethical issues.1,2 In many resource-constrained countries the number of individuals infected with HIV in need of treatment far exceeds the supply of ARV medication. Resource allocation decisions can be made on the basis of many epidemiological,ethical, or preferential treatment priority criteria,Healthcare systems and funding in low-income countries are limited, requiring a step-by-step aipproach to scalingup programs to reach their stated aims.

  18. Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America

    Directory of Open Access Journals (Sweden)

    Carina Cesar

    2016-03-01

    Full Text Available Introduction: Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods: HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet sites were compared to Latino patients (based on country of origin or ethnic identity starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results: The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years, more likely to be female (27% vs. 20% and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all. In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR 1.61; 95% confidence interval (CI: 1.32 to 1.96, particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50, change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62 and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57. Conclusions: HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.

  19. Safety profile of HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 analysis

    Directory of Open Access Journals (Sweden)

    Jacob Lalezari

    2014-11-01

    Full Text Available Introduction: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into the host CD4+ T-cell. AI438011 is an ongoing, Phase IIb, randomized, active-controlled trial investigating the safety, efficacy and dose–response of BMS-663068 vs. atazanavir/ritonavir (ATV/r in treatment-experienced (TE, HIV-1-positive subjects. At Week 24, response rates across the BMS-663068 arms were consistent with ATV/r. Materials and Methods: Antiretroviral TE subjects (exposure to ≥1 antiretroviral for ≥1 week with susceptibility to all study drugs (including BMS-626529 IC50 100 nM were randomized equally to four BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD and a control arm (ATV/r 300/100 mg QD, with tenofovir disoproxil fumarate (TDF + raltegravir (RAL. The complete safety profile through Week 24 is reported. Results: In total, 251 subjects were treated (BMS-663068, 200; ATV/r, 51. No BMS-663068-related adverse events (AEs led to discontinuation. Grade 2–4 drug-related AEs occurred in 17/200 (8.5% subjects across the BMS-633068 arms; however, these events were mostly single instances and no dose-relationship was seen. Similarly, no noticeable trend for Grade 3–4 laboratory abnormalities was seen and Grade 3–4 hematologic changes and liver chemistry elevations were uncommon (neutropenia, 2.5%; AST/ALT elevations, 1% (n=196. In the ATV/r arm, Grade 2–4 drug-related AEs occurred in 14/51 (27.5% subjects and were mostly secondary to gastrointestinal and/or hepatobiliary disorders. Serious adverse events (SAEs occurred in 13/200 (6.5% and 5/51 (9.8% subjects receiving BMS-663068 and ATV/r, respectively; most were secondary to infections and none were related to study drugs. The most common AE reported for BMS-663068 was headache (28/200, 14%, occurring in 5/51 (10% subjects in the ATV/r arm; in the BMS-663068 arms, this was not dose-related. There were no

  20. Trauma History and Depression Predict Incomplete Adherence to Antiretroviral Therapies in a Low Income Country

    OpenAIRE

    Kathryn Whetten; Kristen Shirey; Brian Wells Pence; Jia Yao; Nathan Thielman; Rachel Whetten; Julie Adams; Bernard Agala; Jan Ostermann; Karen O'Donnell; Amy Hobbie; Venance Maro; Dafrosa Itemba; Elizabeth Reddy

    2013-01-01

    Background As antiretroviral therapy (ART) for HIV becomes increasingly available in low and middle income countries (LMICs), understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care. Methodology Th...

  1. Injury Secondary to Antiretroviral Agents: Retrospective Analysis of a Regional Poison Center Database

    OpenAIRE

    Wheatley, Matthew A; Shah, Bijal B; Morgan, Brent W.; Houry, Debra; Kazzi, Ziad N.

    2011-01-01

    Introduction: Poisoning is an increasingly important cause of injury in the United States. In 2009 poison centers received 2,479,355 exposure reports, underscoring the role of poison centers in intentional and unintentional injury prevention. Antiretroviral (ARV) agents are commonly prescribed drugs known to cause toxicity, yet the frequency of these incidents is unknown. The objectives of this study were to quantify the number of reported cases of toxicity secondary to ARV agents at a region...

  2. Injury Secondary to Antiretroviral Agents: A Retrospective Analysis of a Regional Poison Center Database

    OpenAIRE

    Wheatley, Matthew A; Shah, Bijal B; Morgan, Brent W.; Houry, Debra; Kazzi, Ziad N.

    2011-01-01

    Introduction: Poisoning is an increasingly important cause of injury in the United States. In 2009 poison centers received 2,479,355 exposure reports, underscoring the role of poison centers in intentional and unintentional injury prevention. Antiretroviral (ARV) agents are commonly prescribed drugs known to cause toxicity, yet the frequency of these incidents is unknown. The objectives of this study were to quantify the number of reported cases of toxicity secondary to ARV agents at a region...

  3. The Socio-Political Economy of Antiretroviral Treatment as HIV Prevention

    OpenAIRE

    Class, Deena M.

    2012-01-01

    This doctoral thesis seeks to explore the socio-political economy of antiretroviral treatment (ART) as an HIV prevention strategy in sub-Saharan Africa (SSA) and, specifically, in Mozambique. We begin with a look at the social construction of HIV in SSA as a ‘sexually transmitted disease’ despite its very low transmission efficiency through heterosexual sex. This inordinate focus on sexual transmission in SSA to the exclusion of other routes of transmission (i.e.: blood-borne transmission) no...

  4. Substance abuse, adherence with antiretroviral therapy, and clinical outcomes among HIV-infected individuals

    OpenAIRE

    Lucas, Gregory M.

    2010-01-01

    Substance abuse and addiction are highly prevalent in HIV-infected individuals. Substance abuse is an important comorbidity that affects the delivery and outcomes of HIV medical management. In this paper I will review data examining the associations between substance abuse and HIV treatment and potential strategies to improve outcomes in this population that warrant further investigation. Current - but not past - substance abuse adversely affects engagement in care, acceptance of antiretrovir...

  5. Finding Meaning: HIV Self-Management and Wellbeing among People Taking Antiretroviral Therapy in Uganda.

    OpenAIRE

    Russell, S; Martin, FA; Zalwango, F; Namukwaya, S; Nalugya, R; Muhumuza, R; Katongole, J; Seeley, J.

    2016-01-01

    : The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's self-management of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management...

  6. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy

    OpenAIRE

    Velásquez, Jorge N; Bibiana A Ledesma; Nigro, Monica G; Natalia Vittar; Nestor Rueda; Luis De Carolis; Olga Figueiras; Silvana Carnevale; Marcelo Corti

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 c...

  7. The journey to antiretroviral therapy in Karnataka, India: who was lost on the road?

    OpenAIRE

    Suresh Shastri; Srinath Sathyanarayna; Sharath Burugina Nagaraja; Ajay MV Kumar; Bharat Rewari; Anthony D Harries; Rony Zachariah

    2013-01-01

    Introduction: One important operational challenge facing antiretroviral treatment (ART) programmes in low- and middle-income countries is the loss to follow-up between diagnosis of human immunodeficiency virus (HIV) and initiation of ART. This is a major obstacle to achieving universal access to ART. This study from Karnataka, India, tried to measure such losses by determining the number of HIV-positive individuals diagnosed, the number of them reaching ART centres, the number initiated on AR...

  8. A Mediation Model to Explain HIV Antiretroviral Adherence Among Gay and Bisexual Men

    OpenAIRE

    Halkitis, Perry N.; Palamar, Joseph

    2008-01-01

    Based on quantitative data describing a sample of 300 HIV seropositive gay and bisexual men living in New York City who were on antiretroviral drug therapy, variables of interest were collapsed into 4 latent constructs–SES (including health care provision), psychological states, drug use impairment, and HIV treatment adherence–and structural equation modeling was used to test the relations among them. Our model indicated a complex interplay between socioeconomic factors, drug use impairment, ...

  9. Scaling up antiretroviral therapy in Uganda: using supply chain management to appraise health systems strengthening

    OpenAIRE

    Neuhann Florian; Waiswa Peter; Windisch Ricarda; Scheibe Florian; de Savigny Don

    2011-01-01

    Abstract Background Strengthened national health systems are necessary for effective and sustained expansion of antiretroviral therapy (ART). ART and its supply chain management in Uganda are largely based on parallel and externally supported efforts. The question arises whether systems are being strengthened to sustain access to ART. This study applies systems thinking to assess supply chain management, the role of external support and whether investments create the needed synergies to stren...

  10. Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy*

    OpenAIRE

    Brewinski, Margaret; Megazzini, Karen; Freimanis Hance, Laura; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa; Hazra, Rohan

    2010-01-01

    In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercho...

  11. Brain structural and functional recovery following initiation of combination antiretroviral therapy

    OpenAIRE

    Becker, James T.; Cuesta, Pablo; Fabrizio, Melissa; Sudre, Gustavo; Vergis, Emanuel N.; Douaihy, Antoine; Bajo Breton, Ricardo; Schubert, Allie; Lopez, Oscar L.; Parkkonen, Lauri; Maestú, Fernando; Bagic, Anto

    2012-01-01

    NeuroAIDS persists in the era of combination antiretroviral therapies. We describe here the recovery of brain structure and function following 6 months of therapy in a treatment-naive patient presenting with HIV-associated dementia. The patient’s neuropsychological test performance improved and his total brain volume increased by more than 5 %. Neuronal functional connectivity measured by magnetoencephalography changed from a pattern identical to that observed in other HIV-infected individual...

  12. ART adherence clubs: a long-term retention strategy for clinically stable patients receiving antiretroviral therapy

    OpenAIRE

    Wilkinson, Lynne Susan

    2013-01-01

    The ART-adherence club model described here provides patient-friendly access to antiretroviral therapy (ART) for clinically stable patients. It reduces the burden that stable patients place on healthcare facilities, increasing clinical human resources for new patients, and those clinically unstable and at risk of failing treatment. In the model, 30 patients are allocated to an ART club. The group meets either at a facility or community venue for less than an hour every 2 months. Group meeting...

  13. Adherence to antiretroviral therapy: a qualitative study with physicians from Rio de Janeiro, Brazil

    OpenAIRE

    Malta Monica; Petersen Maya L; Clair Scott; Freitas Fernando; Bastos Francisco I

    2005-01-01

    Brazil provides free antiretroviral (ARV) therapy to some 150,000 individuals living with HIV/ AIDS). ARV regimens require optimal adherence to achieve undetectable viral loads and to avoid viral resistance. Physicians play a key role to foster ARV adherence, but until now little is known about the communication between physicians/ people living with HIV/AIDS in this setting. In-depth interviews were conducted with 40 physicians treating people living with HIV/AIDS at six public reference cen...

  14. What makes orphans in Kigali, Rwanda, non-adherent to antiretroviral therapy? Perspectives of their caregivers

    OpenAIRE

    Kimiyo Kikuchi; Poudel, Krishna C; John Muganda; Tomoko Sato; Vincent Mutabazi; Ribakare Muhayimpundu; Adolphe Majyambere; Nyonsenga, Simon P; Eriko Sase; Masamine Jimba

    2014-01-01

    Introduction: Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relat...

  15. A Qualitative Study of Patient Motivation to Adhere to Combination Antiretroviral Therapy in South Africa

    OpenAIRE

    van Loggerenberg, F; Gray, D.; Gengiah, S; Kunene, P; Gengiah, TN; Naidoo, K.; Grant, AD

    2015-01-01

    Taken as prescribed, that is, with high adherence, combination antiretroviral therapy (ART) has changed HIV infection and disease from being a sure predictor of death to a manageable chronic illness. Adherence, however, is difficult to achieve and maintain. The CAPRISA 058 study was conducted between 2007 and 2009 to test the efficacy of individualized motivational counselling to enhance ART adherence in South Africa. As part of the overall trial, a qualitative sub-study was conducted, includ...

  16. Laboratory Quality Audit in 25 Anti-Retroviral Therapy Facilities in North West of Nigeria

    OpenAIRE

    Feyisayo Ebenezer Jegede; Henry Akwen Mbah; Timothy Nathaniel Yakubu; Oluwasanmi Adedokun; Olubunmi Ruth Negedu-Momoh; Kwasi Torpey

    2014-01-01

    Introduction: A laboratory’s ability to consistently produce high-quality and reliable results hinges on adopting laboratory standards that guide daily practices to ensure steady quality improvement. Although assessment is an extremely rewarding exercise in health care quality improvement processes, it is always considered very time consuming and expensive in developing world settings. A quarterly internal audit was conducted in 25 FHI360 supported Antiretroviral Treatment laboratories in the...

  17. Standardized representation, visualization and searchable repository of antiretroviral treatment-change episodes

    OpenAIRE

    Rhee Soo-Yon; Blanco Jose; Liu Tommy F; Pere Iñaki; Kaiser Rolf; Zazzi Maurizio; Incardona Francesca; Towner William; Gatell Josep; De Luca Andrea; Fessel W; Shafer Robert W

    2012-01-01

    Abstract Background To identify the determinants of successful antiretroviral (ARV) therapy, researchers study the virological responses to treatment-change episodes (TCEs) accompanied by baseline plasma HIV-1 RNA levels, CD4+ T lymphocyte counts, and genotypic resistance data. Such studies, however, often differ in their inclusion and virological response criteria making direct comparisons of study results problematic. Moreover, the absence of a standard method for representing the data comp...

  18. Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV-1 infection

    OpenAIRE

    Deeks Steven G; Hagberg Lars; Rosengren Lars; Gisslén Magnus; Price Richard W

    2005-01-01

    Abstract Background The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy. We identified subjects who had CSF HIV ...

  19. Neuropathology of HAND With Suppressive Antiretroviral Therapy: Encephalitis and Neurodegeneration Reconsidered

    OpenAIRE

    Gelman, Benjamin B.

    2015-01-01

    HIV-1 infiltrates the central nervous system (CNS) during the initial infection and thereafter plays a persistent role in producing CNS dysfunction as the disease progresses. HIV-associated neurocognitive disorders (HAND) are highly prevalent in HIV-infected patient populations, including currently infected patients with good access to suppressive antiretroviral therapy (cART). cART decreased the severity of CNS dysfunction dramatically and, in doing so, upended the neuropathological foundati...

  20. Effects of Hormonal Contraception on Anti-Retroviral Drug Metabolism, Pharmacokinetics and Pharmacodynamics

    OpenAIRE

    THURMAN, Andrea Ries; Anderson, Sharon; Doncel, Gustavo F.

    2014-01-01

    Among women, human immunodeficiency virus type 1 (HIV-1) infection is most prevalent in those of reproductive age. These women are also at risk of unintended or mistimed pregnancies. Hormonal contraceptives (HCs) are one of the most commonly used methods of family planning world-wide. Therefore concurrent use of HC among women on anti-retroviral medications (ARVs) is increasingly common. ARVs are being investigated and have been approved for pre-exposure prophylaxis (PrEP), and therefore drug...

  1. When to start antiretroviral therapy in resource-limited settings: a human rights analysis

    OpenAIRE

    Calmy Alexandra; Ford Nathan; Hurst Samia

    2010-01-01

    Abstract Background Recent evidence from developed and developing countries shows clear clinical and public health benefit to starting antiretroviral therapy (ART) earlier. While discussions about when to start ART have often focused on the clinical risks and benefits, the main issue is one of fair limit-setting. We applied a human rights framework to assess a policy of early treatment initiation according to the following criteria: public-health purpose; likely effectiveness; specificity; hu...

  2. Effectiveness and Safety of Concurrent Use of First-Line Antiretroviral and Antituberculous Drugs in Rwanda

    OpenAIRE

    Justin Ntokamunda Kadima; Marie Françoise Mukanyangezi; Claude Bernard Uwizeye

    2014-01-01

    Background. Overlapping toxicity between drugs used for HIV and TB could complicate the management of HIV/TB coinfected patients, particularly those carrying multiple opportunistic infections. This study aimed to evaluate the clinical outcomes and adverse drug events in HIV patients managed with first-line antiretroviral and first-line anti-TB drugs. Methods. This is a retrospective study utilizing medical dossiers from single-HIV infected and HIV/TB coinfected patients already initiated on A...

  3. Barriers to and Facilitators of Antiretroviral Therapy Adherence in Nepal: A Qualitative Study

    OpenAIRE

    Wasti, Sharada P.; Simkhada, Padam; Randall, Julian; Freeman, Jennifer V.; van Teijlingen, Edwin

    2012-01-01

    Patient's adherence is crucial to get the best out of antiretroviral therapy (ART). This study explores in-depth the barriers to and facilitators of ART adherence among Nepalese patients and service providers prescribing ART. Face-to-face semi-structured interviews were conducted with 34 participants. Interviews were audio-taped, transcribed, and translated into English before being analyzed thematically. ART-prescribed patients described a range of barriers for failing to adhere to ART. Fina...

  4. Patient and Regimen Characteristics Associated with Self-Reported Nonadherence to Antiretroviral Therapy

    OpenAIRE

    Sullivan, Patrick S.; Campsmith, Michael L; Nakamura, Glenn V.; Begley, Elin B.; Schulden, Jeffrey; Nakashima, Allyn K.

    2007-01-01

    Background Nonadherence to antiretroviral therapy (ARVT) is an important behavioral determinant of the success of ARVT. Nonadherence may lead to virological failure, and increases the risk of development of drug resistance. Understanding the prevalence of nonadherence and associated factors is important to inform secondary HIV prevention efforts. Methodology/Principal Findings We used data from a cross-sectional interview study of persons with HIV conducted in 18 U.S. states from 2000–2004. W...

  5. Modelling the Impact of Antiretroviral Therapy on the Epidemic of HIV

    OpenAIRE

    Williams, Brian G; Lima, Viviane; Gouws, Eleanor

    2011-01-01

    Thirty years after HIV first appeared it has killed close to 30 million people but transmission continues unchecked. In 2009, an estimated 1.8 million lives were lost and 2.6 million more people were infected with HIV [1]. To cut transmission, many social, behavioural and biomedical interventions have been developed, tested and tried but have had little impact on the epidemic in most countries. One substantial success has been the development of combination antiretroviral therapy (ART) that r...

  6. Treatment modification in HIV-Infected individuals starting antiretroviral therapy between 2011 and 2014

    OpenAIRE

    Michaela Rappold; Armin Rieger; Andrea Steuer; Maria Geit; Mario Sarcletti; Bernhard Haas; Ninon Taylor; Manfred Kanatschnig; Gisela Leierer; Bruno Ledergerber; Robert Zangerle

    2014-01-01

    Introduction: While antiretroviral therapy (ART) has increased the survival of HIV patients and turned HIV infection into a chronic condition, treatment modifications and poor adherence might limit this therapeutic success. Methods: Patients from the Austrian HIV Cohort Study, who started their first ART after Rilpivirine became available in February 2011, were analyzed for factors associated with treatment modification which could be either a change of drugs or a stop of the regimen. A drug ...

  7. Adherence and retention on antiretroviral therapy in a public-private partnership program in Nigeria

    OpenAIRE

    Torpey, K; Ogbanufe, O; Babatunde, F; O Mosuro; A Fajola; Khamofu, H.; Odafe, S.; A Barinaadaa

    2012-01-01

    Initiation of HIV-positive patients on antiretroviral therapy (ART) in Nigeria was restricted to secondary and tertiary level hospitals due to weak health systems in primary health centres (PHCs). Shell Petroleum Development Company (SDPC) Nigeria and FHI 360 using a systems strengthening approach, piloted ART enrolment in a PHC in south-eastern Nigeria. This study sought to evaluate patients’ adherence and mortality on ART, and associated risk factors. We reviewed clinic records of ad...

  8. Human Immunodeficiency Virus Type 1 Cloning Vectors for Antiretroviral Resistance Testing

    OpenAIRE

    Martinez-Picado, Javier; Sutton, Lorraine; De Pasquale, Maria Pia; Savara, Anu V.; D’Aquila, Richard T.

    1999-01-01

    Better detection of minority human immunodeficiency virus type 1 (HIV-1) populations containing gene mutations may improve the usefulness of antiretroviral resistance testing for clinical management. Molecular cloning of HIV-1 PCR products which might improve minority detection can be slow and difficult, and commercially available recombinant virus assays test drug susceptibility of virus pools. We describe novel plasmids and simple methods for rapid cloning of HIV-1 PCR products from patient...

  9. Interaction between Artemether-Lumefantrine and Nevirapine-Based Antiretroviral Therapy in HIV-1-Infected Patients▿

    OpenAIRE

    Kredo, T.; Mauff, K.; Van der Walt, J. S.; Wiesner, L.; G. Maartens; Cohen, K.; Smith, P.; Barnes, K. I.

    2011-01-01

    Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria and HIV, respectively, in Africa. Artemether, lumefantrine, and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces, creating potential for important drug interactions. In a parallel-design pharmacokinetic study, concentration-time profiles were obtained in two groups of HIV-infected patients: ART-naïve patients...

  10. Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy

    OpenAIRE

    Parikh, Sunil; Fehintola, Fatai; Huang, Liusheng; Olson, Alexander; Adedeji, Waheed A.; Darin, Kristin M.; Morse, Gene D.; Robert L Murphy; Taiwo, Babafemi O; Akinyinka, Olusegun O; Adewole, Isaac F.; Aweeka, Francesca T.; Scarsi, Kimberly K.

    2015-01-01

    Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unc...

  11. Evaluation of safety and tolerability of antiretroviral therapy in pregnant and non-pregnant women

    OpenAIRE

    Kamini Tyagi; Veena Gupta

    2015-01-01

    Background: The study was conducted to evaluate safety and tolerability of different components of combined antiretroviral therapy (CART) in pregnant and non-pregnant women and to find out substitute of the drug causing intolerance. Methods: An observational study on 75 pregnant and 125 non pregnant, HIV infected women receiving CART, over a period of 1 year (Jan 2013-Jan 20140 in SRN Hospital affiliated to MLN Medical college, Allahabad. All women were examined clinically and investigated...

  12. Hidden costs of HIV treatment in Spain: inefficiency of the antiretroviral drug packaging

    OpenAIRE

    Llibre-Codina, Josep M; Angels Andreu-Crespo; Gloria Cardona-Peitx; Ferran Sala-Piñol; Bonaventura Clotet-Sala; Xavier Bonafont-Pujol

    2014-01-01

    Introduction: Antiretroviral drugs in Spain are delivered by law only in hospital pharmacies. Commercial packages meet variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems Nearly 20–25% of the initial regimens will be changed at 48 weeks for different reasons. We evaluated the economic impact on public health system of the inability of using returned drugs due to inefficient packaging. Materials and Methods: We defined socially efficient ...

  13. Identifying self-perceived HIV-related stigma in a population accessing antiretroviral therapy

    OpenAIRE

    Tzemis, Despina; Forrest, Jamie I; Puskas, Cathy M; Zhang, Wendy; Orchard, Treena R.; Palmer, Alexis K; McInnes, Colin W; Fernades, Kimberly A.; Montaner, Julio S.G.; Hogg, Robert S.

    2012-01-01

    This study identifies factors associated with self-perceived HIV-related stigma (stigma) among a cohort of individuals accessing antiretroviral therapy (ART) in British Columbia, Canada. Data were drawn from the Longitudinal Investigations into Supportive and Ancillary Health Services study, which collects social, clinical, and quality of life (QoL) information through an interviewer-administered survey. Clinical variables (i.e. CD4 count) were obtained through linkages with the British Colum...

  14. Supporting children to adhere to anti-retroviral therapy in urban Malawi: multi method insights

    OpenAIRE

    Phiri Sam; Chiunguzeni Darles; Nyirenda Jean; Makwiza Ireen; Weigel Ralf; Theobald Sally

    2009-01-01

    Abstract Background Ensuring good adherence is critical to the success of anti-retroviral treatment (ART). However, in resource-poor contexts, where paediatric HIV burden is high there has been limited progress in developing or adapting tools to support adherence for HIV-infected children on ART and their caregivers. We conducted formative research to assess children's adherence and to explore the knowledge, perceptions and attitudes of caregivers towards children's treatment. Methods All chi...

  15. Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

    OpenAIRE

    Balkundi, Shantanu; Nowacek, Ari S.; Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn; Gendelman, Howard E.

    2010-01-01

    Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coat...

  16. Analysis of the evolution of direct costs of antiretroviral delivery in Argentina

    OpenAIRE

    E Bissio; C Balleri; C Falistocco

    2012-01-01

    Background: In Argentina, antiretroviral treatment (ART) is covered by the State for all the persons who do not have health insurances, who represent 70% of all HIV infected patients in the country. Since 1992, the Direction of Aids (Ministry of Health) buys and delivers ART, treatments for opportunistic infections and reagents to diagnose and follow-up HIV infection. Nevertheless, until now, an analysis of the evolution of the costs of the drugs acquired by the Direction of Aids has not been...

  17. Third-line antiretroviral therapy in Africa: effectiveness in a Southern African retrospective cohort study

    OpenAIRE

    Meintjes, Graeme; Dunn, Liezl; Coetsee, Marla; Hislop, Michael; Leisegang, Rory; Regensberg, Leon; Maartens, Gary

    2015-01-01

    Background An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme. Methods Retrospective observational cohort study wi...

  18. Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study

    OpenAIRE

    Christopoulos, Katerina A.; Olender, Susan; Lopez, Andrea M.; Lekas, Helen-Maria; Jaiswal, Jessica; Mellman, Will; Geng, Elvin; Koester, Kimberly A.

    2015-01-01

    Background Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well a...

  19. Sex Differences in HIV Outcomes in the Highly Active Antiretroviral Therapy Era: A Systematic Review

    OpenAIRE

    Castilho, Jessica L; Melekhin, Vlada V.; Sterling, Timothy R

    2014-01-01

    To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses ...

  20. Barriers to Free Antiretroviral Treatment Access for Female Sex Workers in Chennai, India

    OpenAIRE

    Chakrapani, Venkatesan; Newman, Peter A.; Shunmugam, Murali; Kurian, Abraham K.; Dubrow, Robert

    2009-01-01

    India's National AIDS Control Organization (NACO) provides free first-line antiretroviral treatment (ART) at government centers for people living with HIV. To assist in developing policies and programs to ensure equity in ART access, we explored barriers to ART access among female sex workers (FSWs) living with HIV in Chennai. Between August and November 2007, we conducted three focus group discussions and two key informant interviews. Data were explored using framework analysis to identify c...