WorldWideScience

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...

  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 wh...

  3. 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...

  4. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-01

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

  6. 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....

  7. Reconstitution of naive T cells during antiretroviral treatment of HIV-infected adults is dependent on age

    NARCIS (Netherlands)

    Cohen Stuart, James; Hamann, Dörte; Borleffs, Jan; Roos, Marijke; Miedema, Frank; Boucher, Charles; de Boer, Rob

    2002-01-01

    OBJECTIVE: To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART). METHODS: The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45R

  8. Risk of discontinuation of nevirapine due to toxicities in antiretroviral-naive and -experienced HIV-infected patients with high and low CD4+ T-cell counts

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Staszewski, Schlomo; Weber, Rainer;

    2007-01-01

    It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cARTexperienced patients.......It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cARTexperienced patients....

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    BACKGROUND: Patients receiving combination antiretroviral therapy (cART) might continue treatment with a virologically failing regimen. We sought to identify annual change in CD4(+) T-cell count according to levels of viraemia in patients on cART. METHODS: A total of 111,371 CD4(+) T-cell counts ...

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

    Directory of Open Access Journals (Sweden)

    Ana Celia Oliveira dos Santos

    2013-12-01

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

  11. Quantitative analysis of antiretroviral drugs in lysates of peripheral blood mononuclear cells using MALDI-triple quadrupole mass spectrometry.

    NARCIS (Netherlands)

    Kampen, JJ van; Burgers, P.C.; Gruters, R.A.; Osterhaus, A.D.; Groot, R. de; Luider, T.M.; Volmer, D.A.

    2008-01-01

    We report here on the use of a prototype matrix-assisted laser desorption/ionization (MALDI)-triple quadrupole mass spectrometer for quantitative analysis of six antiretroviral drugs in lysates of peripheral blood mononuclear cells (PBMC). Of the five investigated MALDI matrixes, 2,5-dihydroxybenzoi

  12. T-CELL RESPONSE OF ADVANCED AIDS PATIENTS AFTER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

    Institute of Scientific and Technical Information of China (English)

    Ai-xia Wang; Tai-sheng Li; Yun-zhen Cao; Yang Han; Zhi-feng Qiu; Jing Xie

    2005-01-01

    Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy (HAART).Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4+ T cell counts < 100/mm3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4+(naive CD4+ T cell defined by CD45RA+ and CD62L+, memory CD4+ T cell defined by CD45RA-), CD8+ T cell,plasma HIV viral load, and clinical manifestations on before, during, and after HAART (5 different regimes) on 1, 3, 6, 9,and 12 months.Results Before HAART mean CD4+ T cell counts were 32 ± 31 (range 2-91)/mm3, and plasma HIV viral load were 5.07±0.85(range 2.04-5.70) log copies/mL. In 1 month's time patients treated with HAART had mean CD4+ and CD8T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4+ T cells were memory CD4+ T cells, as for naive CD4+ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months' HAART.Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAART.

  13. [The antiretroviral agent Fullevir].

    Science.gov (United States)

    Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D

    2009-01-01

    The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

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

    Directory of Open Access Journals (Sweden)

    Dina Tsukrov

    2016-09-01

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

  15. 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.

  16. Mutagenic and recombinagenic effects of lamivudine and stavudine antiretrovirals in somatic cells of Drosophila melanogaster.

    Science.gov (United States)

    Franchi, Leonardo Pereira; Pentiado, Nádia Helena Garofo Rodrigues; Silva, Renata do Nascimento; Guimarães, Nilza Nascimento; Jesuino, Rosália Santos Amorim; de Andrade, Heloísa Helena Rodrigues; Lehmann, Maurício; Cunha, Kênya Silva

    2009-03-01

    Lamivudine (3TC) and stavudine (d4T) are nucleoside analogue reverse transcriptase inhibitors employed in antiretroviral therapies. The mutational and recombinational potential as well as the total genetic toxicity was determined for both compounds at concentrations allowing at least 30% survival using the standard version of wing SMART assay. The standardized clone induction frequency per mg/ml for mwh/flr(3) genotype were approximately 2 and approximately 33 mutant clones/10(5) cells/(mg/ml) for d4T and 3TC, respectively. Comparing these results with those obtained in the mwh/TM3 genotype, it was possible to quantify the recombinagenic action of each drug. Approximately 86% of the mutant clones induced by 3TC and approximately 76% of the d4T induced clones were related to their mitotic recombination action. Our results indicate that both 3TC and d4T have high recombinagenic potential, and suggest that exposure to the drugs could cause genomic instability and loss of heterozygosity. This may be due to the fact that these genetic alterations play a primary role in carcinogenesis, and are also involved in secondary and subsequent steps of carcinogenesis by which recessive oncogenic mutations are revealed.

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

    Science.gov (United States)

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

    2015-01-01

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

  18. 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

  19. Antiretroviral therapy in HIV-1-infected individuals with CD4 count below 100 cells/mm3 results in differential recovery of monocyte activation.

    Science.gov (United States)

    Patro, Sean C; Azzoni, Livio; Joseph, Jocelin; Fair, Matthew G; Sierra-Madero, Juan G; Rassool, Mohammed S; Sanne, Ian; Montaner, Luis J

    2016-07-01

    Reversal of monocyte and macrophage activation and the relationship to viral suppression and T cell activation are unknown in patients with advanced HIV-1 infection, initiating antiretroviral therapy. This study aimed to determine whether reduction in biomarkers of monocyte and macrophage activation would be reduced in conjunction with viral suppression and resolution of T cell activation. Furthermore, we hypothesized that the addition of CCR5 antagonism (by maraviroc) would mediate greater reduction of monocyte/macrophage activation markers than suppressive antiretroviral therapy alone. In the CCR5 antagonism to decrease the incidence of immune reconstitution inflammatory syndrome study, antiretroviral therapy-naïve patients received maraviroc or placebo in addition to standard antiretroviral therapy. PBMCs and plasma from 65 patients were assessed during 24 wk of antiretroviral therapy for biomarkers of monocyte and macrophage activation. Markers of monocyte and macrophage activation were reduced significantly by 24 wk, including CD14(++)CD16(+) intermediate monocytes (P CCR5-positive monocytes in PBMC. HIV-1 suppression after 24 wk of antiretroviral therapy, with or without maraviroc, demonstrates robust recovery in monocyte subset activation markers, whereas soluble markers of activation demonstrate minimal decrease, qualitatively differentiating markers of monocyte/macrophage activation in advanced disease.

  20. Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy▿

    Science.gov (United States)

    Knox, Kenneth S.; Vinton, Carol; Hage, Chadi A.; Kohli, Lisa M.; Twigg, Homer L.; Klatt, Nichole R.; Zwickl, Beth; Waltz, Jeffrey; Goldman, Mitchell; Douek, Daniel C.; Brenchley, Jason M.

    2010-01-01

    The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells. PMID:20610726

  1. Antiretroviral therapy suppressed participants with low CD4+ T-cell counts segregate according to opposite immunological phenotypes

    Science.gov (United States)

    Pérez-Santiago, Josué; Ouchi, Dan; Urrea, Victor; Carrillo, Jorge; Cabrera, Cecilia; Villà-Freixa, Jordi; Puig, Jordi; Paredes, Roger; Negredo, Eugènia; Clotet, Bonaventura; Massanella, Marta; Blanco, Julià

    2016-01-01

    Background: The failure to increase CD4+ T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4+ T-cell homeostasis and impacts clinical evolution. Methods: We evaluated different definitions of immunodiscordance based on CD4+ T-cell counts (cutoff) or CD4+ T-cell increases from nadir value (ΔCD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals. Results: Cutoff definition of CD4+ cell count 400 cells/μl performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4+ T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4+ T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4+ T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4+ values were maintained in these participants over time. Conclusion: A cutoff value of CD4+ T-cell count 400 cells/μl classified better immunodiscordant and immunoconcordant individuals than any ΔCD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup

  2. Modulation of polyfunctional HIV-specific CD8 T cells in patients responding differently to antiretroviral therapy.

    Science.gov (United States)

    Casetti, R; De Simone, G; Sacchi, A; Bordoni, V; Viola, D; Rinaldi, A; Agrati, C; Gioia, C; Martini, F

    2014-01-01

    Antiretroviral therapy allows a restoration of immune cell homeostasis associated with a normal immune competence. Our goal was to analyze the modulation of polyfunctional HIV-specific CD8+ T-cell responses during antiretroviral therapy. HIV-infected individuals were divided into four groups according to CD4+ cell count and viral load at the moment of recruitment. Whole blood was stimulated with a pool of CD8-specific HIV-antigens to assess cytokine/chemokine production and cytotoxicity activity by using flow cytometry. The groups show different modulation in HIV-specific CD8+ T-cell responses. In particular, immunological failure showed different distributions of polyfunctional HIVspecific CD8+ responses, mainly due to an increase of cells producing CD107alpha/IFNgamma/IL-2/MIP-1beta. Our results indicate that this particular 4+ functional subset is a possible correlate of immunological failure. Considering the complexity of interactions among HAART, immune system and HIV, work is in progress to find correlates of therapy efficacy.

  3. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Decreased NK Cell FcRgamma in HIV-1 infected individuals receiving combination antiretroviral therapy: a cross sectional study.

    Directory of Open Access Journals (Sweden)

    Edwin Leeansyah

    Full Text Available BACKGROUND: FcRgamma is an immunoreceptor tyrosine-based activation motif (ITAM-signalling protein essential for immunoreceptor signaling and monocyte, macrophage and NK cell function. Previous study from our laboratory showed that FcRgamma is down-regulated in HIV-infected macrophages in vitro. FcRgamma expression in immune cells present in HIV-infected individuals is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We compared FcRgamma expression in peripheral blood mononuclear cells isolated from HIV-1-infected individuals receiving combination antiretroviral therapy and healthy, HIV-1-uninfected individuals. FcRgamma mRNA and protein levels were measured using quantitative real-time PCR and immunoblotting, respectively. CD56(+ CD94(+ lymphocytes isolated from blood of HIV-1 infected individuals had reduced FcRgamma protein expression compared to HIV-uninfected individuals (decrease = 76.8%, n = 18 and n = 12 respectively, p = 0.0036. In a second group of patients, highly purified NK cells had reduced FcRgamma protein expression compared to uninfected controls (decrease = 50.2%, n = 9 and n = 8 respectively, p = 0.021. Decreased FcRgamma expression in CD56+CD94+ lymphocytes was associated with reduced mRNA (51.7%, p = 0.021 but this was not observed for the smaller group of patients analysed for NK cell expression (p = 0.36. CONCLUSION/SIGNIFICANCE: These data suggest biochemical defects in ITAM-dependent signalling within NK cells in HIV-infected individuals which is present in the context of treatment with combination antiretroviral therapy.

  6. Influence of antiretroviral therapy on programmed death-1 (CD279) expression on T cells in lymph nodes of human immunodeficiency virus-infected individuals.

    Science.gov (United States)

    Ehrhard, Simone; Wernli, Marion; Dürmüller, Ursula; Battegay, Manuel; Gudat, Fred; Erb, Peter

    2009-10-01

    Human immunodeficiency virus infection leads to T-cell exhaustion and involution of lymphoid tissue. Recently, the programmed death-1 pathway was found to be crucial for virus-specific T-cell exhaustion during human immunodeficiency virus infection. Programmed death-1 expression was elevated on human immunodeficiency virus-specific peripheral blood CD8+ and CD4+ T cells and correlated with disease severity. During human immunodeficiency infection, lymphoid tissue acts as a major viral reservoir and is an important site for viral replication, but it is also essential for regulatory processes important for immune recovery. We compared programmed death-1 expression in 2 consecutive inguinal lymph nodes of 14 patients, excised before antiretroviral therapy (antiretroviral therapy as of 1997-1999) and 16 to 20 months under antiretroviral therapy. In analogy to lymph nodes of human immunodeficiency virus-negative individuals, in all treated patients, the germinal center area decreased, whereas the number of germinal centers did not significantly change. Programmed death-1 expression was mostly found in germinal centers. The absolute extent of programmed death 1 expression per section was not significantly altered after antiretroviral therapy resulting in a significant-relative increase of programmed death 1 per shrunken germinal center. In colocalization studies, CD45R0+ cells that include helper/inducer T cells strongly expressed programmed death-1 before and during therapy, whereas CD8+ T cells, fewer in numbers, showed a weak expression for programmed death-1. Thus, although antiretroviral therapy seems to reduce the number of programmed death-1-positive CD8+ T lymphocytes within germinal centers, it does not down-regulate programmed death-1 expression on the helper/inducer T-cell subset that may remain exhausted and therefore unable to trigger immune recovery.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  9. 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...

  10. Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy

    Science.gov (United States)

    Fleury, S.; Rizzardi, G. P.; Chapuis, A.; Tambussi, G.; Knabenhans, C.; Simeoni, E.; Meuwly, J.-Y.; Corpataux, J.-M.; Lazzarin, A.; Miedema, F.; Pantaleo, G.

    2000-01-01

    The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4+ T lymphocytes, i.e., CD4+Ki67+ T lymphocytes, was not significantly different in HIV-infected (n = 73) and HIV-negative (n = 15) subjects, whereas proliferating CD8+Ki67+ T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4+Ki67+ T lymphocytes increased over time and was associated with an increase of both naive and memory CD4+ T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4+ T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART. PMID:10805798

  11. Dual Pressure from Antiretroviral Therapy and Cell-Mediated Immune Response on the Human Immunodeficiency Virus Type 1 Protease Gene

    Science.gov (United States)

    Karlsson, Annika C.; Deeks, Steven G.; Barbour, Jason D.; Heiken, Brandon D.; Younger, Sophie R.; Hoh, Rebecca; Lane, Meghan; Sällberg, Matti; Ortiz, Gabriel M.; Demarest, James F.; Liegler, Teri; Grant, Robert M.; Martin, Jeffrey N.; Nixon, Douglas F.

    2003-01-01

    Human immunodeficiency virus (HIV)-specific CD8+ T-lymphocyte pressure can lead to the development of viral escape mutants, with consequent loss of immune control. Antiretroviral drugs also exert selection pressures on HIV, leading to the emergence of drug resistance mutations and increased levels of viral replication. We have determined a minimal epitope of HIV protease, amino acids 76 to 84, towards which a CD8+ T-lymphocyte response is directed. This epitope, which is HLA-A2 restricted, includes two amino acids that commonly mutate (V82A and I84V) in the face of protease inhibitor therapy. Among 29 HIV-infected patients who were treated with protease inhibitors and who had developed resistance to these drugs, we show that the wild-type PR82V76-84 epitope is commonly recognized by cytotoxic T lymphocytes (CTL) in HLA-A2-positive patients and that the CTL directed to this epitope are of high avidity. In contrast, the mutant PR82A76-84 epitope is generally not recognized by wild-type-specific CTL, or when recognized it is of low to moderate avidity, suggesting that the protease inhibitor-selected V82A mutation acts both as a CTL and protease inhibitor escape mutant. Paradoxically, the absence of a mutation at position 82 was associated with the presence of a high-avidity CD8+ T-cell response to the wild-type virus sequence. Our results indicate that both HIV type 1-specific CD8+ T cells and antiretroviral drugs provide complex pressures on the same amino acid sequence of the HIV protease gene and, thus, can influence viral sequence evolution. PMID:12767994

  12. 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.

  13. Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells

    Directory of Open Access Journals (Sweden)

    Kellie N. Smith

    2016-05-01

    Full Text Available Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART. Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL. A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control. Here we report that naive CD8+ T cells from chronic HIV-1-infected participants on long-term cART can be primed by dendritic cells (DC. These DC must be mature, produce high levels of interleukin 12p70 (IL-12p70, be responsive to CD40 ligand (CD40L, and be loaded with inactivated, autologous HIV-1. These DC-primed CD8+ T cell responders produced high levels of gamma interferon (IFN-γ in response to a broad range of both conserved and variable regions of Gag and effectively killed CD4+ T cell targets that were either infected with the autologous latent reservoir-associated virus or loaded with autologous Gag peptides. In contrast, HIV-1-specific memory CD8+ T cells stimulated with autologous HIV-1-loaded DC produced IFN-γ in response to a narrow range of conserved and variable Gag peptides compared to the primed T cells and most notably, displayed significantly lower cytolytic function. Our findings highlight the need to selectively induce new HIV-1-specific CTL from naive precursors while avoiding activation of existing, dysfunctional memory T cells in potential curative immunotherapeutic strategies for HIV-1 infection.

  14. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    Science.gov (United States)

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.

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

    Science.gov (United States)

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

    2015-12-01

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

  16. The CYP2B6 G516T polymorphism influences CD4+ T-cell counts in HIV-positive patients receiving antiretroviral therapy in an ethnically diverse region of the Amazon

    Directory of Open Access Journals (Sweden)

    Maria Alice Freitas Queiroz

    2017-02-01

    Conclusions: The CYP2B6 G516T polymorphism seems to affect the response to efavirenz treatment by reducing CD4+ T-cell counts in patients with a high degree of miscegenation who use this antiretroviral agent.

  17. Early and Delayed Antiretroviral Therapy (ART) Result in Comparable Reductions in CD8+ T Cell Exhaustion Marker Expression.

    Science.gov (United States)

    Rutishauser, Rachel; Hartogensis, Wendy; Deguit, Christian D; Krone, Melissa; Hoh, Rebecca; Hecht, Rick; Pilcher, Christopher D; Bacchetti, Peter; Deeks, Steven G; Hunt, Peter W; McCune, Joseph M

    2017-03-23

    In untreated HIV infection, CD8+ T cell exhaustion (i.e., decreased proliferative and effector capacity) is associated with high levels of expression of co-inhibitory receptors, including PD-1, TIGIT, CD160, and 2B4. This is evident for both HIV-specific and non-HIV-specific CD8+ T cells. Antiretroviral therapy (ART) initiated during chronic infection decreases but may not completely normalize the expression of such "exhaustion markers." Compared to initiation of ART later in the course of disease, initiation soon after infection reduces some parameters of chronic inflammation and adaptive immune dysfunction. However, it is not known if Early ART (e.g., initiated within the first six months after HIV infection) versus Delayed ART (e.g., initiated during chronic infection) preferentially reduces expression of exhaustion markers. We evaluated exhaustion marker expression on subsets of circulating effector and memory CD8+ T cells at longitudinal pre- and post-ART (two and five years on ART) time points from n=19 (Early ART) and n=23 (Delayed ART) individuals. Prior to ART, TIGIT and CD160 were expressed on a statistically significantly higher proportion of effector and transitional memory cells from individuals in the Delayed ART group: the timing of ART initiation, however, did not consistently affect the expression of the exhaustion markers once viral suppression was achieved. Understanding which factors do and do not regulate aspects of CD8+ T cell exhaustion, including the expression of exhaustion markers, is critical to inform the rational design of CD8+ T cell-based therapies to treat HIV, for which CD8+ T cell exhaustion remains an important barrier to efficacy.

  18. Relationship between regulatory T cells and immune activation in human immunodeficiency virus-infected patients interrupting antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Laurence Weiss

    Full Text Available UNLABELLED: Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV disease progression. Whether CD4+CD25+ regulatory T cells (Tregs are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART. Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI (ANRS 116. Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12 of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r=-0.519. Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p=0.029; absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p=0.031. At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI. TRIAL REGISTRATION: ClinicalTrials.gov NCT00118677.

  19. 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 HIV-1 replication on cART may harbor HL....

  20. Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease.

    Directory of Open Access Journals (Sweden)

    Brinda Emu

    Full Text Available The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4∶CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/µl ("non-controllers", n = 42, those with undetectable viral loads on ART ("ART-suppressed", n = 53, and HIV-uninfected subjects (n = 22. In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4∶CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all comparisons. The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD28-CD27-CD45RA+/-CCR7- T cell subpopulations persisted despite ART and minimal changes were noted in naïve T cell frequencies over time. Increased number of CD8+CD28- T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4∶CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN-γ. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating different proliferative responses in the setting of T cell depletion. In summary, this study demonstrated that CD4∶CD8 ratios remained significantly decreased and naïve T cell numbers were slow to increase despite long-term viral suppression on ART. In addition, there is a evidence of differential regulation of the CD4+ and CD8+ T cell subpopulations, suggesting independent homeostatic regulation of

  1. 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.

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

    DEFF Research Database (Denmark)

    Jensen, Sanne Skov; Fomsgaard, Anders; Borggren, Marie

    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...... during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART....

  3. Total lymphocyte count is a reliable surrogate marker for CD4 cell counts after the first year of antiretroviral therapy: data from an Indonesian cohort study.

    Science.gov (United States)

    de Jong, Marrigje A; Wisaksana, Rudi; Meijerink, Hinta; Indrati, Agnes; van de Ven, Andre J A M; Alisjahbana, Bachti; van Crevel, Reinout

    2012-05-01

    Many studies have evaluated the total lymphocyte count (TLC) as a cheap surrogate marker for CD4 cells in HIV-infected patients not receiving antiretroviral therapy (ART). We assessed whether TLC can replace CD4 cell counts in evaluating the immunological response to ART. In a cohort of patients in Indonesia TLC, if measured after at least 1-year ART, correctly identified patients with <200 CD4 cells, and reliably excluded immunological failure, obviating the need for CD4 cell measurement in 43% of patients.

  4. Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy

    Science.gov (United States)

    Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George

    2017-01-01

    ABSTRACT Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Recombinant human growth hormone (rhGH) administered to combination antiretroviral therapy (cART)-treated human immunodeficiency virus-1 (HIV-1)-infected individuals has been found to reverse thymic involution, increase total and naïve CD4 T-cell counts, and to reduce the expression of activation...... were used to enumerate HIV-1-specific IFN-γ-producing T cells at baseline and week 40. Individuals who received rhGH demonstrated increased responses to HIV-1 Gag overlapping 20mer and Gag 9mer peptide pools at week 40 compared to baseline, whereas subjects who received placebo showed no functional...

  6. Maternal CD4+ Cell Count Decline after Interruption of Antiretroviral Prophylaxis for the Prevention of Mother-to-Child Transmission of HIV

    Science.gov (United States)

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

    2012-01-01

    Background We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program. Methods Analysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm3 at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm3 or <200 cells/mm3 at 24 months. Weibull regression was used for multivariable analysis. Findings A total of 1,393 women with enrollment CD4+ ≥250 cells/mm3 initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23–30), median CD4+ was 469 cells/mm3 (IQR: 363–613). At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm3 was 12% (95% CI: 10–14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm3 was 28%; (95% CI: 25–32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm3: 46% (CD4+400–499 cells/mm3) vs. 19% (CD4+ ≥500 cells/mm3). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm3 within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5–3.2, p<0.0001). Conclusion Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery. PMID:22952754

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

    Directory of Open Access Journals (Sweden)

    Didier Ekouevi

    Full Text Available BACKGROUND: We evaluated maternal CD4+ cell count (CD4+ decline after PMTCT prophylaxis in a multi-country HIV care program. METHODS: Analysis was restricted to antiretroviral therapy (ART-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm(3 at enrollment. Single-dose nevirapine (sd-NVP or short-course antiretroviral prophylaxis (sc-ARVp with zidovudine (AZT or AZT + lamivudine (3TC was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp (AZT+3TC+ NVP or nelfinavir. All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm(3 or <200 cells/mm(3 at 24 months. Weibull regression was used for multivariable analysis. FINDINGS: A total of 1,393 women with enrollment CD4+ ≥250 cells/mm(3 initiated tARVp (172; 12% or sc-ARVp (532; 38% during pregnancy or received intrapartum sd-NVP (689; 50%. At enrollment, maternal median age was 27 years (interquartile range (IQR 23-30, median CD4+ was 469 cells/mm(3 (IQR: 363-613. At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm(3 was 12% (95% CI: 10-14. Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm(3 was 28%; (95% CI: 25-32. Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm(3: 46% (CD4+400-499 cells/mm(3 vs. 19% (CD4+ ≥500 cells/mm(3. After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm(3 within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5-3.2, p<0.0001. CONCLUSION: Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.

  8. 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 ...

  9. Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Griffin, Daniel O.; Metzger, Michael; Poeth, Kaitlin; Deng, Kathy; Dharsee, Arif; Rico, Juan Carlos; McGowan, Joseph

    2015-01-01

    Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival of <2 months from time of diagnosis. PMID:26566539

  10. Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response

    Directory of Open Access Journals (Sweden)

    Rayk Behrendt

    2013-08-01

    Full Text Available Aicardi-Goutières syndrome (AGS, a hereditary autoimmune disease, clinically and biochemically overlaps with systemic lupus erythematosus (SLE and, like SLE, is characterized by spontaneous type I interferon (IFN production. The finding that defects of intracellular nucleases cause AGS led to the concept that intracellular accumulation of nucleic acids triggers inappropriate production of type I IFN and autoimmunity. AGS can also be caused by defects of SAMHD1, a 3′ exonuclease and deoxynucleotide (dNTP triphosphohydrolase. Human SAMHD1 is an HIV-1 restriction factor that hydrolyzes dNTPs and decreases their concentration below the levels required for retroviral reverse transcription. We show in gene-targeted mice that also mouse SAMHD1 reduces cellular dNTP concentrations and restricts retroviral replication in lymphocytes, macrophages, and dendritic cells. Importantly, the absence of SAMHD1 triggered IFN-β-dependent transcriptional upregulation of type I IFN-inducible genes in various cell types indicative of spontaneous IFN production. SAMHD1-deficient mice may be instrumental for elucidating the mechanisms that trigger pathogenic type I IFN responses in AGS and SLE.

  11. When to start antiretroviral therapy

    DEFF Research Database (Denmark)

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

    2013-01-01

    , 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......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...

  12. 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

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

    Science.gov (United States)

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

    2015-01-01

    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 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 before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.

  14. Intensification of antiretroviral therapy with a CCR5 antagonist in patients with chronic HIV-1 infection: effect on T cells latently infected.

    Directory of Open Access Journals (Sweden)

    Carolina Gutiérrez

    Full Text Available OBJECTIVE: The primary objective was to assess the effect of MVC intensification on latently infected CD4(+ T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. METHODS: We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells, and markers associated with bacterial translocation. RESULTS: Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068. A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4(+ or CD8(+ counts, although a significant decrease was found in the proportion of HLA-DR(+/CD38(+ CD4(+ and CD8(+ T-cells. LPS and sCD14 levels increased. CONCLUSIONS: Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. TRIAL REGISTRATION: ClinicalTrials.gov NCT00795444.

  15. 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....

  16. Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy

    DEFF Research Database (Denmark)

    Gaardbo, J.C.; Nielsen, S.D.; Vedel, S.J.;

    2008-01-01

    mechanisms. During recent years it has become evident that a subpopulation of T cells [T regulatory (T(regs))] play a major role in sustaining tolerance to self-antigens. To investigate the influence of initiation of highly active anti-retroviral therapy (HAART) on the T(reg) level in HIV-infected patients...

  17. 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...

  18. Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype.

    Science.gov (United States)

    Riou, Catherine; Tanko, Ramla F; Soares, Andreia P; Masson, Lindi; Werner, Lise; Garrett, Nigel J; Samsunder, Natasha; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Burgers, Wendy A

    2015-09-01

    Antiretroviral therapy (ART) induces rapid suppression of viral replication and a progressive replenishment of CD4(+) T cells in HIV-infected individuals. However, the effect of ART on restoring pre-existing memory CD4(+) T cells specific for common copathogens is still unclear. To better understand the dynamics of Ag-specific CD4(+) T cells during ART, we assessed the frequency, functional capacity, and memory profile of CD4(+) T cells specific for Mycobacterium tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART initiation. After ART initiation, the frequency of M. tuberculosis-specific CD4(+) T cells showed little change, whereas CMV-specific CD4(+) T cells were significantly lower (p = 0.003). There was no difference in the polyfunctional or memory profile of Ag-specific CD4(+) T cells before and after ART. The replenishment of Ag-specific CD4(+) T cells correlated with the memory differentiation profile of these cells prior to ART. Pathogen-specific CD4(+) T cells exhibiting a late differentiated profile (CD45RO(+)CD27(-)) had a lower capacity to replenish (p = 0.019; r = -0.5) compared with cells with an early differentiated profile (CD45RO(+)CD27(+); p = 0.04; r = 0.45). In conclusion, restoration of copathogen-specific memory CD4(+) T cells during treated HIV infection is related to their memory phenotype, in which early differentiated cells (such as most M. tuberculosis-specific cells) have a higher replenishment capacity compared with late differentiated cells (such as most CMV-specific cells). These data identify an important, hitherto unrecognized, factor that may limit restoration of copathogen immunity in HIV-infected individuals on ART.

  19. Effect of prolonged discontinuation of successful antiretroviral therapy on CD4+ T cell decline in human immunodeficiency virus-infected patients: implications for intermittent therapeutic strategies.

    Science.gov (United States)

    Tebas, Pablo; Henry, Keith; Mondy, Kristin; Deeks, Steven; Valdez, Herman; Cohen, Cal; Powderly, William G

    2002-09-15

    This study evaluates the change in CD4(+) T cell counts among patients who achieved complete viral suppression and subsequently discontinued highly active antiretroviral therapy (HAART). We included 72 human immunodeficiency virus (HIV)-1-infected patients with plasma HIV RNA loads of <500 copies/mL for at least 3 months who then discontinued therapy for at least 12 weeks. The median CD4(+) T decay while off HAART was 16 cells/mm(3)/month (interquartile range, -6 to -34 cells/month). The mean follow-up after therapy ended was 45 weeks. The slope of the CD4(+) T cell decay was inversely correlated with the increase of CD4(+) T cells while receiving HAART, baseline virus load, CD4(+) T cell count at the time therapy was discontinued, age, and duration HIV RNA levels were undetectable. In a multiple regression analysis model, the increase of CD4(+) T cells while receiving therapy and age were independently associated with the rate of CD4(+) T cell loss.

  20. 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

  1. T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.

    Science.gov (United States)

    Buechler, M B; Newman, L P; Chohan, B H; Njoroge, A; Wamalwa, D; Farquhar, C

    2015-09-01

    HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

  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

    2015-01-01

    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...... 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...

  3. Effect of Raltegravir-containing Intensification on HIV Burden and T Cell Activation in Multiple Gut Sites of HIV+ Adults on Suppressive Antiretroviral Therapy

    Science.gov (United States)

    Yukl, Steven A.; Shergill, Amandeep; McQuaid, Kenneth; Gianella, Sara; Lampiris, Harry; Hare, C. Bradley; Pandori, Mark; Sinclair, Elizabeth; Günthard, Huldrych F.; Fischer, Marek; Wong, Joseph K.; Havlir, Diane V.

    2010-01-01

    Objective To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut. Design Open-label study in HIV+ adults on ART with plasma HIV RNA<40 copies/ml. Methods Seven HIV+ adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from PBMC and 4 gut sites, T cell subsets, and activation markers. Results Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, 5 of 7 participants had a decrease in unspliced HIV RNA per 106 CD4+ T cells in the ileum. There was a trend towards decreased T cell activation in all sites, which was greatest for CD8+ T cells in the ileum and PBMC, and a trend towards increased CD4+ T cells in the ileum. Conclusion Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible. PMID:20827162

  4. 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 individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... 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...

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

    Science.gov (United States)

    Jensen, Sanne Skov; 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 (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 ADCC declined during ART. These findings suggest improved cytotoxic function of the NK cells if initiating ART early during infection, while the levels of ADCC mediating antibodies declined during ART.

  6. Antiretroviral (HIV-1) activity of azulene derivatives.

    Science.gov (United States)

    Peet, Julia; Selyutina, Anastasia; Bredihhin, Aleksei

    2016-04-15

    The antiretroviral activity of azulene derivatives was detected for the first time. A series of eighteen diversely substituted azulenes was synthesized and tested in vitro using HIV-1 based virus-like particles (VLPs) and infectious HIV-1 virus in U2OS and TZM-bl cell lines. Among the compounds tested, the 2-hydroxyazulenes demonstrated the most significant activity by inhibiting HIV-1 replication with IC50 of 2-10 and 8-20 μM for the VLPs and the infectious virus, respectively. These results indicate that azulene derivatives may be potentially useful candidates for the development of antiretroviral agents.

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

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Boué, François;

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Bouteloup, V; Sabin, C; Mocroft, A;

    2017-01-01

    OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research...... Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study....... Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9...

  9. Improved antiretroviral treatment outcome in a rural African setting is associated with cART initiation at higher CD4 cell counts and better general health condition

    Directory of Open Access Journals (Sweden)

    Geubbels Eveline

    2011-04-01

    Full Text Available Abstract Background Data on combination antiretroviral therapy (cART in remote rural African regions is increasing. Methods We assessed prospectively initial cART in HIV-infected adults treated from 2005 to 2008 at St. Francis Designated District Hospital, Ifakara, Tanzania. Adherence was assisted by personal adherence supporters. We estimated risk factors of death or loss to follow-up by Cox regression during the first 12 months of cART. Results Overall, 1,463 individuals initiated cART, which was nevirapine-based in 84.6%. The median age was 40 years (IQR 34-47, 35.4% were males, 7.6% had proven tuberculosis. Median CD4 cell count was 131 cells/μl and 24.8% had WHO stage 4. Median CD4 cell count increased by 61 and 130 cells/μl after 6 and 12 months, respectively. 215 (14.7% patients modified their treatment, mostly due to toxicity (56%, in particular polyneuropathy and anemia. Overall, 129 patients died (8.8% and 189 (12.9% were lost to follow-up. In a multivariate analysis, low CD4 cells at starting cART were associated with poorer survival and loss to follow-up (HR 1.77, 95% CI 1.15-2.75, p = 0.009; for CD4 100 cells/μl. Higher weight was strongly associated with better survival (HR 0.63, 95% CI 0.51-0.76, p Conclusions cART initiation at higher CD4 cell counts and better general health condition reduces HIV related mortality in a rural African setting. Efforts must be made to promote earlier HIV diagnosis to start cART timely. More research is needed to evaluate effective strategies to follow cART at a peripheral level with limited technical possibilities.

  10. CD4 Variability in Malawi: Implications for Use of a CD4 Threshold of 500 Cells/mm3 Versus Universal Eligibility for Antiretroviral Therapy

    Science.gov (United States)

    Schooley, Alan L.; Kamudumuli, Pocha Samuel; Vangala, Sitaram; Tseng, Chi-hong; Soko, Chifundo; Parent, Julie; Phiri, Khumbo; Jahn, Andreas; Namarika, Dan; Hoffman, Risa M.

    2016-01-01

    Background. Given the uncertainty about the ability of a single CD4 count to accurately classify a patient as antiretroviral therapy (ART) eligible, we sought to understand the extent to which CD4 variability results in misclassification at a CD4 threshold of 500 cells/mm3. Methods. We performed a prospective study of CD4 variability in Malawian human immunodeficiency virus-infected, ART-naive, World Health Organization (WHO) stage 1 or 2, nonpregnant adults. CD4 counts were performed daily for 8 days. We fit a Bayesian linear mixed-effects model of log-transformed CD4 cell counts to the data. We used Monte Carlo approximations to estimate misclassification rates for different observed values of CD4. The misclassification rate was calculated based on the conditional probability of true CD4 given the geometric mean of observed CD4 measurements. Results. Fifty patients were enrolled from 2 sites. The median age was 33.5 years (interquartile range, 27.5–40.0) and 34 (68%) were female. Misclassification rates were <1% when the observed CD4 counts were ≤250 or ≥750 cells/mm3. Rates of misclassification were high at observed CD4 counts between 350 and 650 cells/mm3, particularly when a single measurement was used (up to 46.7%). Conclusions. Our data show that ART eligibility based on a single CD4 count results in highest risk of misclassification when observed CD4 counts are in the range of 350–650 cells/mm3. Given the benefits of early ART, countries should weigh the costs and complexity of CD4 testing using a 500 cell/mm3 threshold against the cost savings and public health benefits of universal eligibility. PMID:27704028

  11. 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.

  12. 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.......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....

  13. Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.

    Directory of Open Access Journals (Sweden)

    Cristina Cellerai

    Full Text Available BACKGROUND: Intervention with antiretroviral treatment (ART and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+ and CD8(+ T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+ and CD8(+ T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8(+ T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden. CONCLUSIONS: Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Steven Baveewo

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

  16. Antiretrovirals for developing world.

    Science.gov (United States)

    Adler, M W

    1998-01-24

    The most recent UNAIDS figures indicate that approximately 30 million people are infected with HIV worldwide, 5.8 million of whom were newly infected during 1997. At the 10th International Conference on AIDS and Sexually Transmitted Diseases in Africa, the President and Secretary of Health of France called upon developed countries to establish a Therapeutic Assistance Fund to make antiretrovirals available to people with HIV/AIDS in sub-Saharan Africa. While the annual per capita health budget in most African countries is less than US$10, triple antiretroviral therapy against AIDS in the developed world costs $12,000-14,000 per patient per year. Calculations based upon a lower per patient cost of $7000, and treating all 1.4 million African AIDS cases, would cost US$10 billion per year for drugs alone, more than 30 times the amount currently spent annually by international donors for AIDS programs in the entire developing world. Basic infrastructural requirements would have to be met were antiretrovirals made widely available, ranging from HIV screening and counseling to the provision of clean water with which to consume the required 20-30 tablets per day. High program costs will challenge long-term sustainability. Universal access to care and treatment for HIV infection and AIDS is not a reality in the developed world, let alone feasible in developing countries. Given the competing health care priorities in developing countries, the high costs of antiretroviral agents, poor infrastructure, and inability to sustain such a program, the French initiative is ill-advised and foolish public health practice.

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

    Directory of Open Access Journals (Sweden)

    Datsen George Wei

    2014-04-01

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

  18. 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 loador=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......-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients...

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

    Directory of Open Access Journals (Sweden)

    Jeffy George

    2015-01-01

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

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Subhra Mandal

    2015-08-01

    Full Text Available 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 (<500 ng/ml and that release was sustained for a minimum of 4 days of treatment. Therefore, high drug assimilation and sustained release properties of PLGA-NPs make them an attractive vehicle for cARV nano-drug delivery with the potential to reduce drug dosage as well as the number of drug administrations per month.

  2. 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 (<500 ng/ml) and that release was sustained for a minimum of 4 days of treatment. Therefore, high drug assimilation and sustained release properties of PLGA-NPs make them an attractive vehicle for cARV nano-drug delivery with the potential to reduce drug dosage as well as the number of drug administrations per month.

  3. Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

    Science.gov (United States)

    Anderson, Motswedi; Gaseitsiwe, Simani; Moyo, Sikhulile; Thami, Kerapetse P.; Mohammed, Terence; Setlhare, Ditiro; Sebunya, Theresa K.; Powell, Eleanor A.; Makhema, Joseph; Blackard, Jason T.; Marlink, Richard; Essex, Max; Musonda, Rosemary M.

    2016-01-01

    Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana. Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques. Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively. Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens.

  4. Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy?

    DEFF Research Database (Denmark)

    Kirk, O; Lundgren, Jens Dilling; Pedersen, C;

    1999-01-01

    BACKGROUND: In the 'USPHS/IDSA Guidelines for Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus', the indications for chemoprophylaxis are based on nadir CD4 cell count. Many patients have, however, experienced an increase in CD4 cell count after....../100 PY follow-up (95% confidence interval, 0.0-3.2). No cases of cerebral toxoplasmosis, cytomegalovirus chorioretinitis, or disseminated Mycobacterium avium infection were observed. Follow-up time for these was, however, limited. CONCLUSION: PCP-chemoprophylaxis can be safely discontinued after HAART...

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

    DEFF Research Database (Denmark)

    Dam Nielsen, S; Kjaer Ersboll, A; Mathiesen, Lars Reinhardt;

    1998-01-01

    -infected patients were determined prior to HAART and after 2, 4, 8, and 12 weeks of therapy. The mean number of colony-forming units (cells) per milliliter (cfu/mL) was 15.0 prior to HAART vs. 109.8 in healthy controls (Pcfu/mL increased to 100.3 (Pcfu...

  6. Addition of maraviroc to antiretroviral therapy decreased interferon-γ mRNA in the CD4+ T cells of patients with suboptimal CD4+ T-cell recovery.

    Science.gov (United States)

    Minami, Rumi; Takahama, Soichiro; Kaku, Yu; Yamamoto, Masahiro

    2017-01-01

    The CCR5 antagonist, maraviroc (MVC), is associated with an enhanced CD4+ T-cell response independent of virological suppression; however, its mechanism of action has not been elucidated. In this study, we confirmed the effect of MVC on CD4+ T-cell count recovery in immunological non-responders, and compared the conventional combination antiretroviral therapy (cART) with MVC-intensified cART. We also investigated the effect of MVC on interferon-γ (IFN-γ) production in CD4+ T cells in vitro and in vivo, and evaluated the relationship between the mRNA level of IFN-γ and the degree of CD4+ T-cell count recovery. In vitro analysis indicated that MVC significantly decreased mRNA levels of IFN-γ in HIV-Tat stimulated CD4+ T cells from healthy donor peripheral blood mononuclear cells. Of the 18 HIV-infected patients treated with MVC-intensified cART, 12 had a significantly increased CD4+ T-cell count after 24 weeks of additional treatment with MVC. In patients exhibiting a response in CD4+ T-cell counts, mRNA levels of IFN-γ in CD4+ T cells were lower than those in patients showing a non-response at baseline and at week 24, while mRNA levels of IFN-γ decreased in both groups at 24 weeks. In conclusion, MVC decreased the mRNA level of IFN-γ in CD4+ T cells in vitro and in vivo, especially in patients whose CD4+ T-cell count increased significantly. We also found that the lower baseline IFN-γ mRNA level and the larger decreased rate of IFN-γ mRNA in CD4+ T cells were associated with a good response to MVC regarding CD4+ T-cell recovery.

  7. 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....

  8. 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.

  9. 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....... Furthermore, the fraction of naive CD4 cells increased. These findings have implications for the design of immunotherapy or gene therapy protocols....

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

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C;

    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...

  11. HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

    Directory of Open Access Journals (Sweden)

    Sergio Serrano-Villar

    2014-05-01

    Full Text Available A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3 is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+ and senescence (CD28- and CD57+CD28-, and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years. After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.

  12. Reconstitution of intestinal CD4 and Th17 T cells in antiretroviral therapy suppressed HIV-infected subjects: implication for residual immune activation from the results of a clinical trial.

    Directory of Open Access Journals (Sweden)

    Gabriella d'Ettorre

    Full Text Available INTRODUCTION: During HIV infection the severe depletion of intestinal CD4+ T-cells is associated with microbial translocation, systemic immune activation, and disease progression. This study examined intestinal and peripheral CD4+ T-cell subsets reconstitution under combined antiretroviral therapy (cART, and systemic immune activation markers. METHODS: This longitudinal single-arm pilot study evaluates CD4+ T cells, including Th1 and Th17, in gut and blood and soluble markers for inflammation in HIV-infected individuals before (M0 and after eight (M8 months of cART. From January 2010 to December 2011, 10 HIV-1 naïve patients were screened and 9 enrolled. Blood and gut CD4+ T-cells subsets and cellular immune activation were determined by flow-cytometry and plasma soluble CD14 by ELISA. CD4+ Th17 cells were detected in gut biopsies by immunohistochemistry. Microbial translocation was measured by limulus-amebocyte-lysate assay to detect bacterial lipopolysaccharide (LPS and PCR Real Time to detect plasma bacterial 16S rDNA. RESULTS: Eight months of cART increased intestinal CD4+ and Th17 cells and reduced levels of T-cell activation and proliferation. The magnitude of intestinal CD4+ T-cell reconstitution correlated with the reduction of plasma LPS. Importantly, the magnitude of Th17 cells reconstitution correlated directly with blood CD4+ T-cell recovery. CONCLUSION: Short-term antiretroviral therapy resulted in a significant increase in the levels of total and Th17 CD4+ T-cells in the gut mucosa and in decline of T-cell activation. The observation that pre-treatment levels of CD4+ and of CD8+ T-cell activation are predictors of the magnitude of Th17 cell reconstitution following cART provides further rationale for an early initiation of cART in HIV-infected individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT02097381.

  13. 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.

  14. 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;

    2013-01-01

    . 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......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...

  15. 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.

  16. 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.

  17. Cardiovascular risks of antiretroviral therapies.

    Science.gov (United States)

    Mondy, Kristin; Tebas, Pablo

    2007-01-01

    The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.

  18. 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.

  19. 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.

  20. 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

  1. Effect of combination antiretroviral therapy on cytomegalovirus retinitis

    Directory of Open Access Journals (Sweden)

    Banker Alay

    2002-01-01

    Full Text Available Purpose: To study the various changes in the course of cytomegalovirus (CMV retinitis following combination antiretroviral treatment. Methods: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were> 100/mm3 for 3 months. Results: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3 at baseline to 175.5/mm3 (range, 97-410/mm3 at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7% patients had immune recovery vitritis. Conclusion: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment

  2. Nuclear Factor of Activated T Cells and Cytokines Gene Expression of the T Cells in AIDS Patients with Immune Reconstitution Inflammatory Syndrome during Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Chen, Heling; Xie, Yirui; Su, Junwei; Huang, Ying; Xu, Lijun; Yin, Michael; Zhou, Qihui

    2017-01-01

    Background. The etiology of immune reconstitution inflammatory syndrome (IRIS) in AIDS patients after the initiation of HAART remains unknown. Several researches indicated that the development of IRIS is associated with the production and variation of cytokines, whose gene expression are closely related to the Ca2+/CN-nuclear factor of activated T cells (NFAT) pathway. Methods. We studied the expression of NFAT isoforms and their major target cytokines genes in peripheral blood CD3+ T cells of subjects through fluorescence quantitative PCR and explored the expression changes of these genes before and after HAART. Results. After the initiation of HARRT, NFAT1, IL-6, and IL-8 gene expression showed a reversal trend in the CD3+ T cells of the IRIS group and changed from low expression before HARRT to high expression after HARRT. In particular, the relative gene expression of NFAT1 was markedly higher compared with the other three isoforms. The IRIS group also showed higher NFAT4, NFAT2, NFAT1, IL-1β, IL-10, IL-2, IL-18, and TNF-α gene expression than the non-IRIS group. Conclusion. This study suggested that high expression levels of IL-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, IL-12, and IL-18 can predict the risk of IRIS. The increased expression of NFAT1 and NFAT4 may promote the expression of cytokines, such as IL-6, IL-8, and TNF-α, which may promote the occurrence of IRIS.

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

    Directory of Open Access Journals (Sweden)

    John Zaunders

    2016-10-01

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

  4. 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....... Furthermore, the fraction of naive CD4 cells increased. These findings have implications for the design of immunotherapy or gene therapy protocols....... 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...

  5. Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive hiv-infected individuals with CD4 cell counts between 50 and 250/mm3

    Directory of Open Access Journals (Sweden)

    LEWI David S.

    2000-01-01

    Full Text Available Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h, zidovidine alone (200 mg q8h or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0.0001. Over a median follow-up of 52 weeks (up to 99 weeks, percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  7. AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in Côte d’Ivoire

    Science.gov (United States)

    Minga, Albert; Gabillard, Delphine; Ouassa, Timothée; Messou, Eugene; Morris, Brandon; Traore, Moussa; Coulibaly, Ali; Freedberg, Kenneth A.; Lewden, Charlotte; Ménan, Hervé; Abo, Yao; Dakoury-Dogbo, Nicole; Toure, Siaka; Seyler, Catherine

    2012-01-01

    Background. In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count–specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)–infected adults with high CD4 cell counts. In sub–Saharan Africa, these CD4 cell count–specific estimates are scarce. Methods. From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d’Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/μL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count–specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. Results. Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500–649, 350–499, 200–349, 100–199, 50–99, and 0–49 cells/μL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/μL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200–349 and ≥650 cells/μL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). Conclusions. Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/μL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub–Saharan Africa. PMID:22173233

  8. 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.

  9. 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.

  10. 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

  11. Antiretroviral adherence and virological outcomes in HIV-positive patients in Ugu district, KwaZulu-Natal province.

    Science.gov (United States)

    Kapiamba, Germain; Masango, Thembekile; Mphuthi, Ditaba

    2016-09-01

    Adherence to antiretroviral therapy is crucial to ensure viral suppression. In the scientific community it is widely accepted that an adherence level of at least 90% is necessary to achieve viral suppression. This study uses pharmacy refill records to describe antiretroviral adherence in HIV-positive patients in Ugu District, KwaZulu-Natal, South Africa and to describe pharmacy refill records as reliable monitoring method of antiretroviral therapy. In total, 61 patients' records were reviewed. Overall, 50 (82%) of the patients achieved an optimum adherence level of at least 90%, whereas 19 (38%) of these patients did not show any related viral suppression. A statistically significant relationship between adherence and viral suppression was not demonstrated. Therefore, pharmacy refill records cannot be recommended as an alternative method of monitoring response to antiretroviral therapy, but laboratory tests including CD4 cell count and or viral load must be combined with the pharmacy refill method for monitoring of antiretroviral therapy in HIV-positive patients.

  12. Characterization of the virus-cell interactions by HIV-1 subtype C variants from an antiretroviral therapy-naïve subject with baseline resistance to the CCR5 inhibitor maraviroc

    DEFF Research Database (Denmark)

    Jakobsen, Martin Roelsgaard

    The CCR5 inhibitor maraviroc (MVC) exerts its antiviral activity by binding to- and altering the conformation of the CCR5 extracellular loops such that HIV-1 gp120 no longer recognizes CCR5. Viruses that have become resistant to MVC through long-term in vitro culture, or from treatment failure...... resistance to MVC that persisted (as a subset of the viral quasispecies) for approximately 12 months in an antiretroviral therapy-naïve subject infected with HIV-1 subtype C (C-HIV). From a large, longitudinal study of C-HIV Envs (n=323) cloned from 21 subjects experiencing progressive C-HIV infection (see......-pseudotyped luciferase reporter viruses identified one subject (thus far) who harboured R5 Env variants in sequential plasma samples that were only partially inhibited by 10μM MVC (n=4 clones). The maximal percent inhibition (MPI) of these Envs by MVC ranged from 80 to 90% in NP2-CD4/CCR5 cells and PBMC. In contrast...

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

    DEFF Research Database (Denmark)

    Mocroft, A; Phillips, A; Ledergerber, B;

    2006-01-01

    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 consecut......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) ... consecutive measurements with VL patients, were used to compare CD4 cell count changes after adjustment for antiretrovirals, time...... from starting cART, age, CD4 at first VL patients. The mean annual change in CD4 cell count was +45.5/microl [95% confidence interval (CI...

  14. Characteristics of HIV-1-specific CD8 T-cell responses and their role in loss of viremia in children chronically infected with HIV-1 undergoing highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zheng; ZHAO Qing-xia; FU Jun-liang; YAO Jin-xia; HE Yun; JIN Lei; WANG Fu-sheng

    2006-01-01

    Background Few studies have examined the properties of human immunodeficiency virus type 1 (HIV-1) epitope-specific cytotoxic T lymphocyte (CTL) responses in children. To address this issue, we characterized epitope-specific CTL responses and analyzed the determinants that may affect CTL responses before and after highly active antiretroviral therapy (HAART) in children with HIV-1 infection.Methods A total of 22 HIV-1-infected children and 23 uninfected healthy children as control were enrolled in the study. Circulating CD4 T cells and HIV-1 RNA load in plasma were routinely measured. Peripheral HIV-1-specific CTL frequency and HIV-1 epitope-specific, interferon-γ (IFN-γ)-producing T lymphocytes were measured using tetramer staining and enzyme-linked immunospot (ELISPOT) assay, respectively.Circulating dendritic cell (DC) subsets were monitored with FACS analysis.Results More than 80% of the children with HIV-1 infection exhibited a positive HIV-1-epitope-specific CTL response at baseline, but HIV-specific CTLs and IFN-γ-producing lymphocytes decreased in patients who responded to HAART in comparison with non-responders and HAART-naive children. The duration of virus suppression resulted from HAART was inversely correlated with CTL frequency. While in HAART-naive children, HIV-1-specific CTL frequency was positively correlated with myeloid DC (mDC) frequency,although the cause and effect relationship between the DCs and CTLs remains unknown.Conclusions HIV-1-epitope-specific CTL responses are dependent on antigenic stimulation. The impaired DC subsets in blood might result in a defect in DC-mediated T cell responses. These findings may provide insight into understanding the factors and related mechanisms that influence the outcome of HIV-1 carriers to HAART or future antiviral therapies.

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

    DEFF Research Database (Denmark)

    Tauriainen, Johanna; Scharf, Lydia; Frederiksen, Juliet;

    2017-01-01

    increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality...... and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T...... cells, despite early ART. These findings highlight the importance of the TIGIT/CD226/PVR axis as an immune checkpoint barrier that could hinder future "cure" strategies requiring potent HIV-specific CD8+ T cells....

  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; Torti, Carlo;

    2013-01-01

    Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure.......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. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy

    DEFF Research Database (Denmark)

    Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A;

    2009-01-01

    BACKGROUND: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). METHODS: Patients starting NVPc after 1...... to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year...... of starting NVPc and mode of transmission. RESULTS: Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high...

  18. 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.

  19. Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics.

    Science.gov (United States)

    Nowacek, Ari S; McMillan, JoEllyn; Miller, Reagan; Anderson, Alec; Rabinow, Barrett; Gendelman, Howard E

    2010-12-01

    We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release, and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated individual drug release from 15 to >20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people.

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

    OpenAIRE

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

    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 (...

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

    NARCIS (Netherlands)

    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

  2. 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;

    2015-01-01

    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...

  3. Drug interactions between hormonal contraceptives and antiretrovirals

    Science.gov (United States)

    Nanda, Kavita; Stuart, Gretchen S.; Robinson, Jennifer; Gray, Andrew L.; Tepper, Naomi K.; Gaffield, Mary E.

    2017-01-01

    Objective: To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. Design: Systematic review of the published literature. Methods: We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. Results: Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. Conclusion: Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices. PMID:28060009

  4. 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

    NARCIS (Netherlands)

    Ledergerber, B; Lundgren, JD; Walker, AS; Sabin, C; Justice, A; Reiss, P; Mussini, C; Wit, F; Monforte, AD; Weber, R; Fusco, G; Staszewski, S; Law, M; Hogg, R; Lampe, F; Gill, MJ; Castelli, F; Phillips, AN; Castelli, F; Fusco, GP; Gill, MJ; Hogg, R; Lampe, F; Law, M; Ledergerber, B; Lundgren, JD; Monforte, AD; Mussini, C; Phillips, AN; Reiss, P; Staszewski, S; Walker, AS; Rooney, P; Taylor, S; Couldwell, D; Austin, D; Block, M; Clemons, J; Finlayson, R; Law, M; Petoumenos, K; Quan, D; Smith, D; O'Connor, C; Gorton, C; Allen, D; Mulhall, B; Mutimer, K; Smith, D; Keeffe, N; Cooper, D; Carr, A; Miller, J; Pell, C; Ellis, D; Baker, D; Kidd, J; McFarlane, R; Liang, MT; Brown, K; Huffam, S; Savage, J; Morgan, S; Knibbs, P; Sowden, D; Walker, A; Orth, D; Lister, G; Chuah, J; Fankhauser, W; Dickson, B; Bradford, D; Wilson, C; Ree, H; Magon, H; Moore, R; Russell, D; McGovern, G; McNair, R; Bal, J; Fairley, K; Roth, N; Eu, B; Strecker, S; Russell, D; Wood, H; Mijch, A; Hoy, J; Pierce, A; McCormack, C; Watson, K; Medland, N; Daye, J; Mallal, S; French, M; Skett, J; Maxwel, D; Cain, A; Montroni, M; Scalise, G; Costantini, A; Giacometti, A; Tirelli, U; Nasti, G; Pastore, G; Ladisa, N; Perulli, ML; Suter, F; Arici, C; Chiodo, F; Gritti, FM; Colangeli, [No Value; Fiorini, C; Guerra, L; Carosi, G; Cadeo, GP; Castelli, F; Minardi, C; Vangi, D; Rizzardini, G; Migliorino, G; Manconi, PE; Piano, P; Ferraro, T; Scerbo, A; Pizzigallo, E; Ricci, F; Santoro, D; Pusterla, L; Carnevale, G; Galloni, D; Vigano, P; Mena, M; Ghinelli, F; Sighinolfi, L; Leoncini, F; Mazzotta, F; Pozzi, M; Lo Caputo, S; Angarano, G; Grisorio, B; Ferrara, S; Grima, P; Tundo, P; Pagano, G; Piersantelli, N; Alessandrini, A; Piscopo, R; Toti, M; Chigiotti, S; Soscia, F; Taccooni, L; Orani, A; Perini, P; Scasso, A; Vincenti, A; Scalzini, A; Fibbia, G; Moroni, M; Lazzarin, A; Cargnel, A; Vigevani, GM; Caggese, L; Monforte, AD; Tordato, F; Novati, R; Galli, A; Merli, S; Pastecchia, C; Moioli, C; Esposito, R; Mussini, C; Abrescia, N; Chirianni, A; Izzo, C; Piazza, M; De Marco, M; Montesarchio, [No Value; Manzillo, E; Nappa, S; Colomba, A; Abbadessa, [No Value; Prestileo, T; Mancuso, S; Ferrari, C; Pzzaferri, P; Filice, G; Minoli, L; Bruno, R; Maserati, R; Pauluzzi, S; Baldelli, F; Petrelli, E; Cioppi, A; Alberici, F; Ruggieri, A; Menichetti, F; Martinelli, C; De Stefano, C; La Gala, A; Zauli, T; Ballardini, G; Magnani, G; Ursitti, MA; Arlotti, M; Ortolani, P; Ortona, L; Dianzani, F; Ippolito, G; Antinori, A; Antonucci, G; D'Elia, S; Narciso, P; Petrosillo, N; Vullo, [No Value; De Luca, A; Del Forno, L; Zaccarelli, M; De Longis, P; Ciardi, M; D'Offizi, G; Noto, P; Lichtner, M; Capobianchi, MR; Girardi, E; Pezzotti, P; Rezza, G; Mura, MS; Mannazzu, M; Caramello, P; Sinicco, A; Soranzo, ML; Gennero, L; Sciandra, M; Salassa, B; Grossi, PA; Basilico, C; Poggio, A; Bottari, G; Raise, E; Pasquinucci, S; De Lalla, F; Tositti, G; Resta, F; Chimienti, A; Lepri, AC; Bachmann, S; Battegay, M; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Tarr, P; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; de Wolf, F; van Sighem, AI; van Valkengoed, [No Value; Gras, L; Bronsveld, W; Prins, JM; Bos, JC; Schattenkerk, JKME; Godfried, MH; Lange, JMA; Lowe, SH; van der Meer, JTM; Nellen, FJB; Pogany, K; van der Poll, T; Reiss, P; Ruys, TA; Sankatsing, S; van der Valk, M; van Vonderen, MGA; Wit, FWMN; ten Veen, JH; van Dam, PS; Hillebrand-Haverkort, ME; Brinkman, K; Frissen, PHJ; Weigel, HM; Mulder, JW; van Gorp, ECM; Meenhorst, PL; Mairuhu, ATA; Veenstra, J; Danner, SA; Van Agtmael, MA; Claessen, FAP; Geerlings, SE; Perenboom, RM; Richter, C; van der Berg, J; van Leusen, R; Vriesendorp, R; Jeurissen, FJF; Kauffmann, RH; Koger, ELW; Bravenboer, B; Mudrikova, T; Sprenger, HG; Miesen, WMAJ; ten Kate, RW; van Houte, DPF; Leemhuis, MP; Pole, M; Schippers, EF; Schreij, G; van de Geest, S; Verbon, A; Koopmans, PP; Telgt, M; van der Ven, AJAM; van der Ende, Marchina E.; Gyssens, IC; de Marie, S; Nouwen, JL; Juttmann, [No Value; Schneider, MME; Bonten, MJM; Borleffs, JCC; Hoepelman, IM; Jaspers, CAJJ; Schouten, [No Value; Schurink, CAM; Blok, WL; Groenveld, PHP; Jurriaans, S; Back, NKT; Cuijpers, T; Rietra, PJGM; Roozendaal, KJ; Pauw, W; van Zanten, AP; Smits, PHM; von Blomberg, BME; Savelkoul, P; Zaaijer, H; Swanink, C; Franck, PFH; Lampe, AS; Jansen, CL; Hendriks, R; Schirm, J; Benne, D; Veenendaal, D; Storm, H; van Zeijl, JH; Claas, HCJ; Bruggeman, CAMVA; Goossens, VJ; Galama, JMD; Poort, YAGM; Niesters, MG; Osterhaus, ADME; Buiting, AGM; Swaans, CAM; Boucher, CAB; Schuurman, R; Boel, E; Jansz, AF; Veldkamp, A; Beijnen, JH; Crommentuyn, KML; Huitema, ADR; Kappelhoff, B; de Maat, MMR; Burger, DM; Hugen, PWH; Dabis, F; Thiebaut, R; Chene, G; Lawson-Ayayi, S; Meyer, L; Boufassa, F; Hamouda, O; Pezzotti, P; Rezza, G; Touloumi, G; Hatzakis, A; Karafoulidou, A; Katsarou, O; Brettle, R; Del Amo, J; del Romero, J; van Asten, L; van Benthem, B; Prins, M; Coutinho, R; Kirk, O; Pedersen, C; Aguado, IH; Perez-Hoyos, S; Eskild, A; Bruun, JN; Sannes, M; Sabin, C; Lee, C; Johnson, AM; Phillips, AN; Babiker, A; Darbyshire, J; Gill, N; Porter, K; Francioli, P; Vanhems, P; Egger, M; Rickenbach, M; Cooper, D; Kaldor, J; Ashton, L; Cooper, D; Kaldor, J; Ashton, L; Cooper, D; Vizzard, J; Muga, R; Vanhems, P; Gill, J; Cayla, J; de Olalla, PG; Day, NE; De Angelis, D; Porter, K; Babiker, A; Walker, S; Darbyshire, J; Tyrer, F; Beral, [No Value; Coutinho, R; Darbyshire, J; Del Amo, J; Gill, N; Lee, C; Meyer, L; Rezza, G; Raffanti, S; Becker, S; Scarsella, A; Braun, J; Justice, A; Fusco, G; Most, B; Balu, R; Gilbert, L; Fleenor, R; Ising, T; Dieterich, D; Fusco, J; Losso, M; Duran, A; Vetter, N; Clumeck, N; De Wit, S; Kabeya, K; Poll, B; Colebunders, R; Machala, L; Rozsypal, H; Nielsen, J; Lundgren, J; Kirk, O; Olsen, CH; Gerstoft, J; Katzenstein, T; Hansen, ABE; Skinhoj, P; Pedersen, C; Zilmer, K; Rauka, M; Katlama, C; De Sa, M; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Stellbrink, HJ; Miller, [No Value; Staszewski, S; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, [No Value; Burke, M; Pollack, S; Hassoun, J; Sthoeger, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, [No Value; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Castagna, A; Monforte, AD; Viksna, L; Rozentale, B; Chaplinskas, S; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, [No Value; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Wiercinska-Drapalo, A; Boron-Kaczmarska, A; Pynka, M; Beniowski, M; Trocha, H; Smiatacz, T; Antunes, F; Mansinho, K; Maltez, F; Duiculescu, D; Streinu-Cercel, A; Mokras, M; Stanekova, D; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, [No Value; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Zamora, L; Blaxhult, A; Karlsson, A; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Hirschel, B; Schiffer, [No Value; Furrer, H; Chentsova, N; Barton, S; Johnson, AM; Mercey, D; Phillips, A; Youle, M; Johnson, MA; Mocroft, A; Murphy, M; Weber, J; Scullard, G; Fisher, M; Brettle, R; Loveday, C; Clotet, B; Ruiz, L; Staszewski, S; Helm, EB; Carlebach, A; Mosch, M; Muller, A; Haberl, A; Korn, S; Stephan, C; Bickel, M; Gute, P; Locher, L; Lutz, T; Klauke, S; Doerr, HW; Sturmer, M; Sabin, C; Dauer, B; Jennings, B; Alexander, C; Braitstein, P; Chan, K; Cote, H; Gataric, N; Harrigan, PR; Harris, M; Bonner, S; Hogg, R; Montaner, J; O'Shaughnessy, M; Wood, E; Yip, B; Lampe, F; Chaloner, C; Gumley, H; Ransom, D; Sabin, CA; Mocroft, A; Lipman, M; Phillips, AN; Youle, M; Johnson, M; Gill, J; Read, R; Carosi, G; Castelli, F; Paraninfo, G; Casari, S; Pan, A; Patroni, A; Torti, C; Quiros-Roldan, E; Tomasoni, L; Moretti, F; Nasta, P; Uccelli, MC; Cadeo, GP; Bertelli, D; Orani, A; Perini, P; Nigro, M; Rizzardini, G; Migliorino, M; Abeli, C; Mazzotta, F; Suter, F; Maggiolo, F; Arici, C; Ghinelli, F; Sighinolfi, L; Minoli, L; Maserati, R; Novati, S; Tinelli, C; Pastore, G; Ladisa, N; Carnevale, G; Poggio, A; Riccio, G; Mussini, C; Borghi, [No Value; Bedini, A; Esposito, R; ten Napel, C.H.

    2004-01-01

    Background 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 failur

  5. 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....

  6. Mortality, AIDS-morbidity and loss to follow-up by current CD4 cell count among HIV-1 infected adults receiving antiretroviral therapy in Africa and Asia: data from the ANRS 12222 collaboration

    Science.gov (United States)

    Gabillard, Delphine; Lewden, Charlotte; Ndoye, Ibra; Moh, Raoul; Ségéral, Olivier; Tonwe-Gold, Besigin; Etard, Jean-François; Pagnaroat, Men; Fournier-Nicolle, Isabelle; Eholié, Serge; Konate, Issouf; Minga, Albert; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Zannou, Djimon Marcel; Anglaret, Xavier; Laurent, Christian

    2013-01-01

    Background In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses and inform decisions. Methods We pooled data from 13 research cohorts in five sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire and Senegal) and two Asian (Cambodia and Laos) countries. HIV-infected adults (≥18 years) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results Overall 3,917 adults (62% women) on ART were followed-up during 10,154 person-years. In the ≤50, 51-100, 101-200, 201-350, 351-500, 501-650 and >650/mm3 CD4 cells strata, death rates were: 20.6, 11.8, 6.7, 3.3, 1.8, 0.9 and 0.3 per 100 person-years; AIDS rates were: 50.5, 32.9, 11.5, 4.8, 2.8, 2.2 and 2.2 per 100 person-years; and loss to follow-up rates were: 4.9, 6.1, 3.5, 3.1, 2.9, 1.7 and 1.2 per 100 person-years, respectively. Mortality and morbidity were higher during the first year following ART initiation. Conclusion In these resource-limited settings, death and AIDS rates remained substantial after ART initiation, even in individuals with high CD4 cell counts. Ensuring earlier ART initiation and optimizing case finding and treatment for AIDS-defining diseases should be seen as priorities. PMID:23274931

  7. Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: a multicenter, cross-sectional study.

    Science.gov (United States)

    Reynolds, Nancy R; Testa, Marcia A; Marc, Linda G; Chesney, Margaret A; Neidig, Judith L; Smith, Scott R; Vella, Stefano; Robbins, Gregory K

    2004-06-01

    It is widely recognized that adherence to antiretroviral therapy is critical to long-term treatment success, yet rates of adherence to antiretroviral medications are frequently subtherapeutic. Beliefs about antiretroviral therapy and psychosocial characteristics of HIV-positive persons naive to therapy may influence early experience with antiretroviral medication adherence and therefore could be important when designing programs to improve adherence to antiretroviral therapy. As part of a multicenter AIDS Clinical Trial Group (ACTG 384) study, 980 antiretroviral-naive subjects (82% male, 47% White, median age 36 years, and median CD4 cell count 278 cells/mm3) completed a self-administered questionnaire prior to random treatment assignment of initial antiretroviral medications. Measures of symptom distress, general health and well-being, and personal and situational factors including demographic characteristics, social support, self-efficacy, depression, stress, and current adherence to (nonantiretroviral) medications were recorded. Associations among variables were explored using correlation and regression analyses. Beliefs about the importance of antiretroviral adherence and ability to take antiretroviral medications as directed (adherence self-efficacy) were generally positive. Fifty-six percent of the participants were "extremely sure" of their ability to take all medications as directed and 48% were "extremely sure" that antiretroviral nonadherence would cause resistance, but only 37% were as sure that antiretroviral therapy would benefit their health. Less-positive beliefs about antiretroviral therapy adherence were associated with greater stress, depression, and symptom distress. More-positive beliefs about antiretroviral therapy adherence were associated with better scores on health perception, functional health, social-emotional-cognitive function, social support, role function, younger age, and higher education (r values = 0.09-0.24, all p < .001). Among

  8. 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...

  9. HIV entry inhibitors: a new generation of antiretroviral drugs

    Institute of Scientific and Technical Information of China (English)

    Elias KRAMBOVITIS; Filippos PORICHIS; Demetrios A SPANDIDOS

    2005-01-01

    AIDS is presently treatable, and patients can have a good prognosis due to the success of highly active antiretroviral therapy (HAART), but it is still not curable or preventable. High toxicity of HAART, and the emergence of drug resistance add to the imperative to continue research into new strategies and interventions.Considerable progress in the understanding of HIV attachment and entry into host cells has suggested new possibilities for rationally designing agents that interfere with this process. The approval and introduction of the fusion inhibitor enfuvirtide (Fuzeon) for clinical use signals a new era in AIDS therapeutics. Here we review the crucial steps the virus uses to achieve cell entry, which merit attention as potential targets, and the compounds at pre-clinical and clinical development stages, reported to effectively inhibit cell entry.

  10. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV...... entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients...... per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)....

  11. Complications of antiretroviral therapy initiation in hospitalised patients with HIV-associated tuberculosis.

    Directory of Open Access Journals (Sweden)

    Helen van der Plas

    Full Text Available BACKGROUND: HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. METHODS: Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. RESULTS: Between May 2009 and November 2010, 112 patients (60% female, with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm3 (IQR 31-106 and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68% developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. CONCLUSIONS: High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1(st three

  12. 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.

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

    Science.gov (United States)

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

    2002-09-03

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

  14. 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.

  15. Early Combination Antiretroviral Therapy Limits HIV-1 Persistence in Children.

    Science.gov (United States)

    Luzuriaga, Katherine

    2016-01-01

    Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure.

  16. 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.

  17. Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders.

    Science.gov (United States)

    Jensen, Brigid K; Monnerie, Hubert; Mannell, Maggie V; Gannon, Patrick J; Espinoza, Cagla Akay; Erickson, Michelle A; Bruce-Keller, Annadora J; Gelman, Benjamin B; Briand, Lisa A; Pierce, R Christopher; Jordan-Sciutto, Kelly L; Grinspan, Judith B

    2015-11-01

    Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy.

  18. Drug resistance and antiretroviral drug development

    OpenAIRE

    Shafer, Robert W.; Jonathan M Schapiro

    2005-01-01

    As more drugs for treating HIV have become available, drug resistance profiles within antiretroviral drug classes have become increasingly important for researchers developing new drugs and for clinicians integrating new drugs into their clinical practice. In vitro passage experiments and comprehensive phenotypic susceptibility testing are used for the pre-clinical evaluation of drug resistance. Clinical studies are required, however, to delineate the full spectrum of mutations responsible fo...

  19. Interaction of antiretroviral medications with finasteride

    OpenAIRE

    Ward, D.

    2012-01-01

    Antiretroviral medications are known inhibitors and inducers of cytochrome p450 enzymes and can affect levels of non-HIV medications. Finasteride 1 mg (Propecia), which prevents the conversion of testosterone (T) to dihydrotestosterone (DHT) is commonly prescribed for prevention of hair loss. This medication is a substrate of p450 3A4. Its efficacy may therefore be affected by HIV medications which induce or inhibit this enzyme. Levels of DHT to prevent hair loss are not well established, but...

  20. 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.

  1. Delayed HIV diagnosis and initiation of antiretroviral therapy

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... included individuals diagnosed with HIV between 1996 and 2011, aged at least 16 years, with known educational level and at least one CD4 cell count within 6 months of HIV diagnosis. We examined trends by education level in presentation with advanced HIV disease (AHD) (CD4 ... count at cART initiation was lower with poorer educational level. CONCLUSIONS: Socioeconomic inequalities in delayed HIV diagnosis and initiation of cART are present in European countries with universal healthcare systems and individuals with lower educational level do not equally benefit from timely c...

  2. 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

  3. 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...... was sustained. There was no association between plasma viral load and the increase in naive CD4 + cell count. Importantly, baseline naive CD4 + cell count was significantly associated with the change in naive CD4 + cell count, suggesting that the naive cell count at baseline does influence the immunological...

  4. Peripheral neuropathy and antiretroviral drugs.

    Science.gov (United States)

    Dalakas, M C

    2001-03-01

    Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.

  5. 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...... to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs......, 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...

  6. The role of formulation on the pharmacokinetics of antiretroviral drugs

    NARCIS (Netherlands)

    Bastiaans, Diane E T; Cressey, Tim R; Vromans, Herman; Burger, David M

    2014-01-01

    INTRODUCTION: A multitude of antiretroviral drug formulations are now available for HIV-infected adults and children. These formulations include individual and co-formulated drugs, many of which are also supplied in generic versions. Many antiretroviral drugs have a low aqueous solubility and poor b

  7. Interaction of antiretroviral medications with finasteride

    Directory of Open Access Journals (Sweden)

    D Ward

    2012-11-01

    Full Text Available Antiretroviral medications are known inhibitors and inducers of cytochrome p450 enzymes and can affect levels of non-HIV medications. Finasteride 1 mg (Propecia, which prevents the conversion of testosterone (T to dihydrotestosterone (DHT is commonly prescribed for prevention of hair loss. This medication is a substrate of p450 3A4. Its efficacy may therefore be affected by HIV medications which induce or inhibit this enzyme. Levels of DHT to prevent hair loss are not well established, but likely need to be<15–20 ng/dl, or a DHT/T ratio of<0.02. Observational analysis in a private practice, measuring DHT and T levels in patients on finasteride and various antiretrovirals 21 patients were identified. 7 patients were taking protease inhibitors and had DHT levels<12 ng/dL; DHT/T<0.20. Three of these patients decreased their finasteride dose to 1 mg every-other-day and still have DHT <10. 8 patients were taking potent p450 inducers (efavirenz or etravirine and had DHT levels between >20; DHT/T>0.025. Two of these patients increased the dose of finasteride to 2 mg/day and subsequently decreased DHT to 14 and 17. Two additional patients on efavirenz, however, had DHT levels of<15 without dose adjustment. Four patients taking nevirapine, a less potent inducer of p450 had DHT levels of<15, as did one patient on raltegravir, which does not affect CYP450. Antiretrovirals that affect CYP 3A4 may interact with finasteride. While it is unlikely that this interaction is dangerous, it may affect its efficacy of the finasteride. Evaluation of DHT/T levels, and/or dose adjustment of finasteride may be appropriate in men being treated for HIV.

  8. Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).

    Science.gov (United States)

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

    2014-06-01

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

  9. Decrease in immune activation in HIV-infected patients treated with highly active antiretroviral therapy correlates with the function of hematopoietic progenitor cells and the number of naive CD4+ cells

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Ersbøll, A K;

    2000-01-01

    determined. During the study period, the naive CD4+ count and the cloning efficiency increased significantly. Immune activation was found in HIV-infected patients and decreased during HAART. The level of immune activation correlated negatively with both the naive CD4+ count and the function of progenitor...... cells. A negative correlation was found between apoptosis and the naive CD4+ count. Alterations in cytokine production during HAART or correlation between cytokine production and the naive CD4+ count or the cloning efficiency of progenitor cells were not detected. In conclusion, immune activation in HIV...

  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;

    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 patien...

  11. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer...

  12. Accessing antiretroviral therapy for children: Caregivers' voices

    Directory of Open Access Journals (Sweden)

    Margaret (Maggie Williams

    2016-12-01

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

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

    DEFF Research Database (Denmark)

    Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G;

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts...... and human immunodeficiency virus (HIV) RNA between the study arms. METHODS:  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline...... covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. RESULTS:  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23...

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

    DEFF Research Database (Denmark)

    Bannister, WP; Ruiz, L; Loveday, C;

    2006-01-01

    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......, 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 ...-B-infected patients (P=0.334). After adjustment, there was no significant difference in odds of an immunological response (OR: 1.17, 95% CI: 0.73–1.87, P=0.524). CONCLUSIONS: There was no evidence of significant differences in virological or immunological response to cART between patients infected with HIV-1 B...

  15. 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 (TNF...... counts below 200 cells per microliter than individuals with CD4 cell counts above 200 cells per microliter. HIV RNA was the strongest predictor of all cytokine expression in multivariate analysis. ART leads to a decrease in all cytokines to levels close to those of HIV-uninfected individuals. CONCLUSIONS...

  16. Posaconazole: A Review of Drug Interactions with HIV Antiretroviral Agents

    Directory of Open Access Journals (Sweden)

    Mara Poulakos

    2014-03-01

    Full Text Available The purpose of this review is to examine the literature for reports of clinically significant interactions noted amongst HIV antiretroviral medications when coadministered with posaconazole. A literature search was conducted to identify studies addressing drug interactions between posaconazole and HIV antiretroviral medications. Two pharmacokinetic studies and three clinical trials involving the administration of posaconazole to HIV-infected patients were identified. The pharmacokinetic studies involved concomitant administration of either a protease inhibitor (PI or non-nucleoside reverse transcriptase inhibitor (NNRTI. Both studies showed alterations in systemic concentrations of either posaconazole or the HIV antiretroviral when administered together. Of the three clinical trials, all patients were on HIV antiretrovirals. However, their potential interaction with posaconazole was not explored. To date, there is no published literature regarding the interaction between maraviroc or elvitegravir and posaconazole. Dose adjustments for each are recommended when coadministered with strong CYP 3A4 inhibitors or inducers. Currently available literature points to the potential for clinically significant drug interactions when posaconazole is coadministered with HIV antiretrovirals, specifically NNRTIs and PIs. More studies are needed involving a wider range of HIV antiretrovirals to determine the significance of the interaction. Clinicians should be aware of this potentially significant interaction and avoid concomitant administration when possible. When available, consideration should be given to therapeutic drug monitoring of antiretroviral serum concentrations in select patients.

  17. Experiencing antiretroviral adherence: helping healthcare staff better understand adherence to paediatric antiretrovirals

    Directory of Open Access Journals (Sweden)

    Phelps Benjamin R

    2010-12-01

    Full Text Available Abstract Background Lack of adherence to antiretroviral medications is one of the key challenges for paediatric HIV care and treatment programmes. There are few hands-on opportunities for healthcare workers to gain awareness of the psychosocial and logistic challenges that caregivers face when administering daily antiretroviral therapy to children. This article describes an educational activity that allows healthcare workers to simulate this caregiver role. Methods Paediatric formulations of several antiretroviral medications were dispensed to a convenience sample of staff at the Baylor College of Medicine-Bristol-Myers Squibb Children's Clinical Center of Excellence in Mbabane, Swaziland. The amounts of the medications remaining were collected and measured one week later. Adherence rates were calculated. Following the exercise, a brief questionnaire was administered to all staff participants. Results The 27 clinic staff involved in the exercise had varying and low adherence rates over the week during which the exercise was conducted. Leading perceived barriers to adherence included: "family friends don't help me remember/tell me I shouldn't take it" and "forgot". Participants reported that the exercise was useful as it allowed them to better address the challenges faced by paediatric patients and caregivers. Conclusions Promoting good adherence practices among caregivers of children on antiretrovirals is challenging but essential in the treatment of paediatric HIV. Participants in this exercise achieved poor adherence rates, but identified with many of the barriers commonly reported by caregivers. Simulations such as this have the potential to promote awareness of paediatric ARV adherence issues among healthcare staff and ultimately improve adherence support and patient outcomes.

  18. Dominant enrichment of phenotypically activated CD38(+) HLA-DR(+) CD8(+) T cells, rather than CD38(+) HLA-DR(+) CD4(+) T cells, in HIV/HCV coinfected patients on antiretroviral therapy.

    Science.gov (United States)

    d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Serafino, Sara; Giustini, Noemi; Cavallari, Eugenio Nelson; Bianchi, Luigi; Pavone, Paolo; Bellelli, Valeria; Turriziani, Ombretta; Antonelli, Guido; Stroffolini, Tommaso; Vullo, Vincenzo

    2016-08-01

    HIV infection may enhance immune-activation, while little is known regarding the role of HCV infection. This study investigates the impact of HCV in HIV coinfected patients with undetectable viraemia under HAART on the levels of peripheral T cell's immune-activation. We determined T lymphocytes subsets to characterize immune-activation defined as CD38 and/or HLA-DR expression in chronic monoinfected HCV, HIV, and HIV/HCV coinfected subjects. One hundred and fifty six patients were divided into three groups: (i) 77 HIV+ patients; (ii) 50 HCV+ patients; and (iii) 29 coinfected HIV/HCV patients. The level of CD4(+) was significantly higher in HCV+ than in HIV+ or in coinfected HIV/HCV subjects. The frequencies of CD4(+) CD38(+) /HLA-DR(-) , CD4(+) CD38(-) /HLA-DR(+) and CD4(+) CD38(+) /HLA-DR(+) in HIV+ patients were comparable to those measured in coinfected patients, but statistically higher than those observed in HCV+ subjects. The percentage of CD8(+) was comparable in HIV-1+ patients and coinfected HIV/HCV but the results obtained in both groups were significantly higher compared to the results obtained in HCV patients. The level of CD8(+) CD38(+) /HLA-DR(-) showed values lower in HIV+ patients than in that monoinfected HCV and coinfected HIV/HCV patients. The frequencies of CD8(+) CD38(-) /HLA-DR(+) were higher in HIV+ patients compared to HCV+ and coinfected HIV/HCV patients. HIV/HCV coinfected group showed highest levels of CD8(+) CD38(+) /HLA-DR(+) . HIV plays a pivotal role to determine the immune activation in the host. The role of HCV needs of further investigations but our data show that HCV mainly influences the immune-activation of the pool of CD8, but also probably plays a supporting additive effect on CD4 immune-activation. J. Med. Virol. 88:1347-1356, 2016. © 2016 Wiley Periodicals, Inc.

  19. 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

  20. 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.

  1. 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.

  2. Nutritional and metabolic assessment of HIV patients in use of antiretroviral therapy at Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Liana Aguiar Braga

    2010-12-01

    Full Text Available Objective: To evaluate nutritional and metabolic changes in HIV infected (HIV+ patients on use of antiretroviral therapy. Methods:  A cross-sectional descriptive study involving HIV+ patients on use of Highly Active Antiretroviral Therapy (HAART. The demographic data studied were gender, birth date and time of use of antiretroviral medication. Anthropometric variables were weight and height with calculation of body mass index (BMI. Biochemical data were lipid profile, blood glucose, renal function, albumin, uric acid, oxalacetic and pyruvic transaminases and red blood cells count. Results: The study population comprised 70 patients, 36 (51.4% men and 34 (48.6% women with an average time of HAART-use of 34.5 + 16.5 months. We observed a prevalence of 42 (60% healthy weight for BMI, changes in lipid profile and reduction of lean mass in 18 (50% men and increased abdominal obesity in 23 (67.7% women. Conclusion: The studied subjects in use of HAART showed to have loss of subcutaneous fat, lipid changes and higher prevalence of abdominal obesity in women.

  3. 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.

  4. Dynamics of the HIV infection under antiretroviral therapy: A cellular automata approach

    Science.gov (United States)

    González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo

    2013-10-01

    The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.

  5. Rates of inappropriate antiretroviral prescription among injection drug users

    Directory of Open Access Journals (Sweden)

    Bonner Simon

    2007-01-01

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

  6. Cellular automata approach for the dynamics of HIV infection under antiretroviral therapies: The role of the virus diffusion

    Science.gov (United States)

    González, Ramón E. R.; de Figueirêdo, Pedro Hugo; Coutinho, Sérgio

    2013-10-01

    We study a cellular automata model to test the timing of antiretroviral therapy strategies for the dynamics of infection with human immunodeficiency virus (HIV). We focus on the role of virus diffusion when its population is included in previous cellular automata model that describes the dynamics of the lymphocytes cells population during infection. This inclusion allows us to consider the spread of infection by the virus-cell interaction, beyond that which occurs by cell-cell contagion. The results show an acceleration of the infectious process in the absence of treatment, but show better efficiency in reducing the risk of the onset of AIDS when combined antiretroviral therapies are used even with drugs of low effectiveness. Comparison of results with clinical data supports the conclusions of this study.

  7. Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

    OpenAIRE

    Nyasha Bakare; Ivor Ralph Edwards; Andy Stergachis; Shanthi Pal; Holmes, Charles B; Marie Lindquist; Chris Duncombe; Alex Dodoo; Joel Novendstern; Jude Nwokike; Ricardo Kuchenbecker; Aberg, Judith A.; Veronica Miller; Jur Strobos

    2011-01-01

    Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings.

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

    Directory of Open Access Journals (Sweden)

    Suleiman IA

    2016-04-01

    Full Text Available 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-sectional study involved administration of an adapted and pretested questionnaire to 601 consented patients attending the two tertiary health institutions in Bayesla State, Nigeria: The Federal Medical Centre, Yenagoa and the Niger-Delta University Teaching Hospital Okolobiri. The tool was divided into various sections such as socio-demographic data, HIV knowledge and adherence to combined antiretroviral therapy. Information on the patient's CD4+ T cells count was retrieved from their medical records. Adherence was assessed by asking patients to recall their intake of prescribed doses in the last fourteen days and subjects who had 95-100% of the prescribed antiretroviral drugs were considered adherent. Results: Three hundred and forty eight (57.9% of the subjects were females and 253 (42.1% were males. The majority of them, 557 (92.7% have good knowledge of HIV and combined anti-retroviral therapy with a score of 70.0% and above. A larger proportion of the respondents, 441 (73.4%, had ≥95% adherence. Some of the most important reasons giving for missing doses include, “simply forgot” 147 (24.5%, and “wanted to avoid the side-effects of drugs” 33(5.5%. There were remarkable improvements in the immune status of the subjects with an increment in the proportion of the subjects with CD4+ T cells count of greater than 350 cells/mm3 from 33 (5.5% at therapy initiation to 338 (56.3% at study period (p<0.0001. Conclusion: The adherence level of 73.4% was low

  9. Is it time to revise antiretrovirals dosing? a pharmacokinetic viewpoint.

    Science.gov (United States)

    Cattaneo, Dario; Baldelli, Sara; Castoldi, Simone; Charbe, Nitin; Cozzi, Valeria; Fucile, Serena; Clementi, Emilio

    2014-10-23

    We document our experience with therapeutic drug monitoring (TDM) of antiretroviral agents (1807 determinations) carried out as day-by-day clinical practice for the optimization of drug dosing in HIV-infected patients. A significant proportion of patients had lopinavir, atazanavir and nevirapine trough concentrations exceeding the upper therapeutic threshold. Further studies are needed to identify good candidates/drugs for TDM, eventually allowing the selection of patients who may benefit from TDM-driven adjustments in antiretrovirals dosage.

  10. 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...

  11. 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.

  12. Antiretroviral outcomes in South African prisoners: a retrospective cohort analysis.

    Directory of Open Access Journals (Sweden)

    Natasha E C G Davies

    Full Text Available BACKGROUND AND METHODS: Little is known about antiretroviral therapy (ART outcomes in prisoners in Africa. We conducted a retrospective review of outcomes of a large cohort of prisoners referred to a public sector, urban HIV clinic. The review included baseline characteristics, sequential CD4 cell counts and viral load results, complications and co-morbidities, mortality and loss to follow-up up to 96 weeks on ART. FINDINGS: 148 inmates (133 male initiated on ART were included in the study. By week 96 on ART, 73% of all inmates enrolled in the study and 92% of those still accessing care had an undetectable viral load (<400 copies/ml. The median CD4 cell count increased from 122 cells/mm(3 at baseline to 356 cells/mm(3 by 96 weeks. By study end, 96 (65% inmates had ever received tuberculosis (TB therapy with 63 (43% receiving therapy during the study: 28% had a history of TB prior to ART initiation, 33% were on TB therapy at ART initiation and 22% developed TB whilst on ART. Nine (6% inmates died, 7 in the second year on ART. Loss to follow-up (LTF was common: 14 (9% patients were LTF whilst still incarcerated, 11 (7% were LTF post-release and 9 (6% whose movements could not be traced. 16 (11% inmates had inter-correctional facility transfers and 34 (23% were released of whom only 23 (68% returned to the ART clinic for ongoing follow-up. CONCLUSIONS: Inmates responded well to ART, despite a high frequency of TB/HIV co-infection. Attention should be directed towards ensuring eligible prisoners access ART programs promptly and that inter-facility transfers and release procedures facilitate continuity of care. Institutional TB control measures should remain a priority.

  13. Highly active antiretroviral therapy induced adverse drug reactions in Indian human immunodeficiency virus positive patients (RETRACTED by plagiarism

    Directory of Open Access Journals (Sweden)

    Rajesh R

    2011-03-01

    Full Text Available THIS ARTICLE WAS RETRACTED AFTER A PLAGIARISM INVESTIGATIONObjective: To assess the incidence, severity pattern, causality, predictability and preventability of adverse drug reactions (ADRs and to identify risk factors for adverse drug reactions in highly active antiretroviral therapy.Methods: Enrolled patients were intensively monitored for ADRs to highly active antiretroviral therapy. Predictability was assessed based on history of previous exposure to the drug or literature incidence of ADRs. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using modified Hartwig and Siegel scale. Multivariate logistic regressions were used to identify the risk factors for ADRs.Results: Monitoring of 130 retropositive patients by active pharmacovigilance identified 74 ADRs from 57 patients. Anemia and hepatotoxicity were the most commonly observed ADRs. The organ system commonly affected by ADR was red blood cell (21.4%.The ADRs were moderate in 77% of cases. Type A reactions (77% were more common. A total of 10.8% ADRs were definitely preventable. The incidence rate of ADRs (65.9% was highest with Zidovudine + Lamivudine + Nevirapine combination. A total of 84% interruptions to highly active antiretroviral therapy were due to toxicity. CD4 less than 200 cells/µl, female gender and tuberculosis were observed as risk factors for ADRs.Conclusion: Incidence of ADRs in intensively monitored patients was found to be 43.8%. Anemia in HIV patients is an influential risk factor for occurrence of ADRs. With the increasing access to antiretroviral in India, clinicians must focus on early detection and prevention of ADRs to highly active antiretroviral therapy.

  14. The other genome: a systematic review of studies of mitochondrial DNA haplogroups and outcomes of HIV infection and antiretroviral therapy.

    Science.gov (United States)

    Hart, Anna B; Samuels, David C; Hulgan, Todd

    2013-01-01

    Mitochondrial toxicity is implicated in some treatment-limiting antiretroviral therapy complications, and reports of mitochondrial dysfunction in untreated HIV infection suggest antiretroviral therapy independent effects of HIV. Several studies have explored associations between mtDNA haplogroups (patterns of mtDNA polymorphisms) and outcomes of HIV infection and/or antiretroviral therapy, but findings have been inconsistent. We systematically reviewed published studies examining mtDNA haplogroups in HIV-infected persons to summarize reported outcome associations, and to highlight potential future research directions. We identified 21 articles published from 2005-2013. Multiple different phenotypes were studied; most were antiretroviral therapy associated metabolic outcomes (e.g. lipodystrophy, insulin resistance, and dyslipidemia). Haplogroup H was associated with the most outcomes, including AIDS progression, CD4 T-cell recovery, cirrhosis (in hepatitis C coinfection), and metabolic outcomes. This review is the first to focus on the emerging area of mtDNA haplogroups in HIV, and summarizes the published literature on associations between mtDNA haplogroups and clinical outcomes in populations of European and African descent. Several reported associations require replication and ideally biological verification before definitive conclusions can be drawn, but research in this area has the potential to explain outcome disparities and impact clinical management of patients.

  15. 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.

  16. Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Laura Zehnacker

    2014-01-01

    Full Text Available Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required.

  17. 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

    -related processes of inflammation, metabolism, adipose tissue, and muscle. T cell immunosenescence and exhaustion were assessed by flow cytometry analysis of CD8 (+) cells from 43 ART-treated HIV-infected patients (HIV(+)) and ten Controls using markers of differentiation: CD27/CD28; maturation: CD27/CD45RA...... differentiated and mature CD8 (+) T cell phenotypes. PD-1 and KLRG1 expression did not differ between HIV(+) and Controls, but depended on differentiation and maturation stages of the cells. CD8 (+) T cell maturation was associated with age. KLRG1 expression was associated with age, metabolic syndrome, visceral...

  18. Novel antiretroviral combinations in treatment-experienced patients with HIV infection: rationale and results.

    Science.gov (United States)

    Taiwo, Babafemi; Murphy, Robert L; Katlama, Christine

    2010-09-10

    different virological outcomes when patients were switched from lopinavir/ritonavir to raltegravir, but there was an improvement in the lipid profile. Simplifying to darunavir-ritonavir monotherapy after suppression of plasma HIV RNA to <50 copies/mL has been found to be safe with no emergence of resistance in cases of viral rebound, but longer-term data are needed. The initial suggestion that maraviroc may possess unique CD4+ T-cell boosting effects was not confirmed in several clinical trials. Improved understanding of HIV pathogenesis has opened new frontiers for research such as identifying the sources, consequences and optimal management of residual viraemia in those with plasma HIV RNA <50 copies/mL. Globally, however, one of the most urgent priorities is providing the increasing number of treatment-experienced virologically failing patients in RLS with access to optimal treatment, including those treatments based on novel antiretroviral agents.

  19. Increases in pediatric antiretroviral treatment, South Africa 2005-2010.

    Directory of Open Access Journals (Sweden)

    Sandeep D Patel

    Full Text Available BACKGROUND: In South Africa in 2010, about 340,000 children under the age of 15 were infected with HIV. We describe the increase in the treatment of South African pediatric HIV-infected patients assisted by the President's Emergency Plan for AIDS Relief (PEPFAR from 2004 to 2010. METHODS: We reviewed routine program data from PEPFAR-funded implementing partners among persons receiving antiretroviral treatment age 15 years old and less. Data quality was assessed during the reporting period by program officials through routine analysis of trends and logic checks. Based on UNAIDS estimated mortality rates of untreated HIV-infected children, we calculated the number of deaths averted and life-years gained in children under five receiving PEPFAR-assisted antiretroviral treatment. RESULTS: From October 2004 through September 2010, the number of children newly initiated on antiretroviral treatment in PEPFAR-assisted programs increased from 154 to 2,641 per month resulting in an increase from 2,412 children on antiretroviral treatment in September 2005 to 79,416 children in September 2010. Of those children who initiated antiretroviral treatment before September 2009, 0-4 year olds were 1.4 (95% CI: 1.3-1.5 times as likely to transfer out of the program or die as 5-14 year olds; males were 1.3 (95% CI: 1.0-1.7 times as likely to stop treatment as females. Approximately 27,548 years of life were added to children under-five years old from PEPFAR-assisted antiretroviral treatment. CONCLUSIONS: Pediatric antiretroviral treatment in South Africa has increased substantially. However, additional case-finding and a further acceleration in the implementation of pediatric care and treatment services is required to meet the current treatment need.

  20. 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

  1. 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.

  2. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    Science.gov (United States)

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    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 cells/µl and a poor adherence to HAART.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  4. 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...... 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 (ptherapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group...

  5. Potential drug interactions in patients given antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Wendel Mombaque dos Santos

    Full Text Available ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r. Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000 and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00. The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs.

  6. Pharmacokinetics and drug-drug interactions of antiretrovirals: an update.

    Science.gov (United States)

    Dickinson, Laura; Khoo, Saye; Back, David

    2010-01-01

    Current antiretroviral treatment has allowed HIV infection to become a chronic manageable condition with many HIV patients living longer. However, available antiretrovirals are not without limitations, for example the development of resistance and adverse effects. Consequently, new drugs in existing and novel classes are urgently required to provide viable treatment options to patients with few remaining choices. Darunavir, etravirine, maraviroc and raltegravir have been recently approved for treatment-experienced patients and other agents such as rilpivirine, vicriviroc and elvitegravir are currently under phase III study. Clinical studies are necessary to optimise potential treatment combinations and to manage drug-drug interactions to help avoid toxicity or therapy failure. This review aims to summarise the pharmacokinetics and key drug-drug interaction studies for newly available antiretrovirals and those in development. Further information regarding drug-drug interactions of well established antiretrovirals and those recently approved are readily available online at sites such as http://www.hiv-druginteractions.org, http://www.clinicaloptions.com/hiv, http://hivinsite.ucsf.edu. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.

  7. 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.

  8. Predictive factors of antiretroviral treatment French Guiana.

    Science.gov (United States)

    Elenga, Narcisse; Hanf, Matthieu; Nacher, Mathieu

    2012-01-01

    French Guiana is the French territory where the HIV epidemic is most preoccupying. In Cayenne, the mother to child HIV transmission rate was 6% in 2006-2008. Despite free testing and treatment, HIV pregnant women often have delayed or insufficient access to care. The aim of this study was to identify predictive factors of antiretroviral treatmentFrench Guiana) and then to describe their attitudes, practices, and beliefs regarding HIV/AIDS. A case control study was conducted including all deliveries in Cayenne from 2003 to 2010. For each case, a standardized questionnaire including epidemiological, clinical, and biological data was administered. The analysis first described the summary statistics and then bivariate analysis studied the relation of each variable with the outcome. Multivariate analysis adjusted for the confounding factors. Thirty-three women in the first group and 96 in the control group were included in the study. Women born in French Guiana (OR = 5, IC95% = 1.22-20.86, p=0.027) had a high risk of treatment<4 weeks. The other factors associated with treatment<4 weeks in our study were benefiting from food parcels (OR = 12.72, IC95% = 2.07-78.14, p=0.006), consulting a traditional healer when sick (OR = 9.86, IC95% = 2.57-37.88, p= < 0.001), and drug use (OR = 6.27, IC95% = 1.26-31.13, p=0.025). These predictive factors should be considered in prevention programs against mother to child transmission of HIV.

  9. Pharmacokinetic targets of antiretroviral therapy in children and adolescents

    Directory of Open Access Journals (Sweden)

    Michael N. Neely

    2013-06-01

    Full Text Available Large populations of HIV-infected and exposed infants, children and adolescents are increasingly exposed to antiretroviral therapy throughout dramatic changes of the body composition and maturation process in utero, perinatally and during the later growth and development throughout childhood and puberty. The majority of HIV-infected children live in the resource-limited setting where the presence of other significant co-morbidities such as malnutrition, tuberculosis and malaria complicates the selection of the most effective, safe and least toxic combination of antiretroviral drug therapy. This review focuses on the role of the pharmacokinetic factors including clinically important drug-drug interactions on the therapeutic targets of antiretroviral therapy throughout childhood and adolescence. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  10. 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.

  11. Forgiveness of non-adherence to HIV-1 antiretroviral therapy.

    Science.gov (United States)

    Shuter, Jonathan

    2008-04-01

    Superior adherence to HIV-1 antiretroviral therapy is a mainstay of successful HIV management. Studies performed in the early era of highly active antiretroviral therapy demonstrated the need for > or =95% adherence in order to achieve and sustain viral suppression. High rates of viral suppression have been observed at more moderate levels of adherence with newer antiretroviral regimens. The term 'forgiveness' is being used to describe the ability of a regimen to achieve and sustain viral suppression, despite suboptimal adherence. A variety of pharmacological, viral and host properties determine the level of forgiveness of any specific regimen. As the choice of treatment options continues to expand, forgiveness of non-adherence is likely to emerge as an increasingly important factor in therapeutic decision-making.

  12. The (political) economics of antiretroviral treatment in developing countries.

    Science.gov (United States)

    Nattrass, Nicoli J

    2008-12-01

    Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART.

  13. Future implications: Compliance and failure with antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    Patel Atul

    2006-01-01

    Full Text Available HIV management is currently in an era of effective, potent antiretroviral therapy. Modern drug discovery and development have transformed HIV-1 disease into a treatable, chronic infectious disease. Complete suppression of viral replication is critical for long-term durability of antiretroviral therapy. Partial suppression, even at very low levels, is likely to lead to virologic failure and ultimately to the appearance of drug resistance. The relationship between adherence and resistance to HIV antiretroviral therapy is more complex than to state ′non-adherence increases the risk of drug resistance.′ In many patients who fail to respond to initial therapy, the primary reason for failure is their inability to take the prescribed drug regimen or nonadherence.

  14. 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.

  15. Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy.

    Science.gov (United States)

    Wang, Charlene; Abdel-Mohsen, Mohamed; Strain, Matthew C; Lada, Steven M; Yukl, Steven; Cockerham, Leslie R; Pilcher, Christopher D; Hecht, Frederick M; Sinclair, Elizabeth; Liegler, Teri; Richman, Douglas D; Deeks, Steven G; Pillai, Satish K

    2014-12-01

    Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  17. Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy : a meta-analysis

    NARCIS (Netherlands)

    Dunn, DT; Gibb, DM; Duong, T; Babiker, AG; Bulterys, M; Gabiano, C; Galli, L; Giaquinto, C; Harris, DR; Hughes, M; McKinney, R; Mofenson, L; Moye, J; Newell, ML; Pahwa, S; Palumbo, P; Rudin, C; Schluchter, M; Sharland, M; Shearer, W; Thompson, B; Tookey, P

    2003-01-01

    Background Data on the short-term risk of disease progression in HIV-1-infected children are needed to address the question of when to begin combination antiretroviral therapy. We estimated 12-month risks of progression to AIDS and death, by age and most recent measurement of CD4 T-cell percentage (

  18. 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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  20. 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.

  1. 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

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

    Directory of Open Access Journals (Sweden)

    Biadgilign Sibhatu

    2012-05-01

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

  3. Anti-retroviral drugs do not facilitate hepatitis C virus (HCV) infection in vitro.

    Science.gov (United States)

    Sandmann, Lisa; Wilson, Matthew; Back, David; Wedemeyer, Heiner; Manns, Michael P; Steinmann, Eike; Pietschmann, Thomas; von Hahn, Thomas; Ciesek, Sandra

    2012-10-01

    An estimated 4 to 5 million people are co-infected with HIV/HCV worldwide. Recently observed outbreaks of acute HCV infection among HIV-positive men who have sex with men (MSM) have been linked to behavioral factors such as high risk sexual practices and recreational drug use. However, at the molecular level, many drugs such as glucocorticoids or cyclosporine A have been found to modulate viral replication. Thus, it is conceivable that drugs used in highly active antiretroviral therapy (HAART) may heighten susceptibility to HCV infection and contribute to the recent outbreaks. We therefore performed a comprehensive screen of antiretroviral drugs covering all available drug classes both individually and in typical combinations used during HAART to probe for direct effects on HCV cell entry, replication, new particle assembly and release. Importantly, no significant enhancement or inhibition of HCV cell entry, replication or new particle production was detected. While raltegravir and ritonavir boosted atazanavir reduce HCV replication, a tenfold reduction of HCVcc entry by the CCR5 antagonist maraviroc was observed. In conclusion, commonly used HAART agents do not specifically enhance HCV replication. Thus recent epidemic outbreaks of acute HCV in HIV-infected MSM are unlikely to be related to enhancing effects of HAART drugs.

  4. 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.

  5. 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

    to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs...... of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level. CONCLUSION: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially......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...

  6. 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.

  7. Implementation and effectiveness of antiretroviral therapy in Greenland

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  8. 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; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.

    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

  9. Pharmacokinetics of antiretroviral therapy in HIV-1-infected children

    NARCIS (Netherlands)

    P.L.A. Fraaij (Pieter); J.J.A. van Kampen (Jeroen); D.M. Burger (David); R. de Groot (Ronald)

    2005-01-01

    textabstractThe initiation of antiretroviral therapy has resulted in an impressive reduction in the rate of disease progression in AIDS and HIV-1-related deaths in children; however, there are still several major challenges to be faced in order to improve therapy. A major topic that needs to be deal

  10. 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 500,000 Euros 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.

  11. The emergence of drug resistant HIV variants and novel anti-retroviral therapy

    Institute of Scientific and Technical Information of China (English)

    Koosha Paydary; Parisa Khaghani; Sahra Emamzadeh-Fard; SeyedAhmad SeyedAlinaghi; Kazem Baesi

    2013-01-01

    After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world;however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint.

  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. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations of the Panel on Clinical Practices for Treatment of HIV.

    Science.gov (United States)

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

    2002-05-17

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

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

    Directory of Open Access Journals (Sweden)

    Gottfried Hirnschall

    2013-06-01

    Full Text Available 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 populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm3 or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm3; starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation, Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant couples (existing recommendation, pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first-line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once-daily fixed-dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within

  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. Antiretroviral Treatment in HIV-1-Positive Mothers: Neurological Implications in Virus-Free Children

    Science.gov (United States)

    Coelho, Antonio Victor Campos; Tricarico, Paola Maura; Celsi, Fulvio; Crovella, Sergio

    2017-01-01

    Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-“boosted” lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero. PMID:28212307

  18. 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.

  19. The dual role of pharmacogenetics in HIV treatment: mutations and polymorphisms regulating antiretroviral drug resistance and disposition.

    Science.gov (United States)

    Michaud, Veronique; Bar-Magen, Tamara; Turgeon, Jacques; Flockhart, David; Desta, Zeruesenay; Wainberg, Mark A

    2012-07-01

    Significant intra- and interindividual variability has been observed in response to use of pharmacological agents in treatment of HIV infection. Treatment of HIV infection is limited by high rates of adverse drug reactions and development of resistance in a significant proportion of patients as a result of suboptimal drug concentrations. The efficacy of antiretroviral therapy is challenged by the emergence of resistant HIV-1 mutants with reduced susceptibility to antiretroviral drugs. Moreover, pharmacotherapy of patients infected with HIV is challenging because a great number of comorbidities increase polypharmacy and the risk for drug-drug interactions. Drug-metabolizing enzymes and drug transporters regulate drug access to the systemic circulation, target cells, and sanctuary sites. These factors, which determine drug exposure, along with the emergence of mutations conferring resistance to HIV medications, could explain variability in efficacy and adverse drug reactions associated with antiretroviral drugs. In this review, the major factors affecting the disposition of antiretroviral drugs, including key drug-metabolizing enzymes and membrane drug transporters, are outlined. Genetic polymorphisms affecting the activity and/or the expression of cytochromes P450 or UGT isozymes and membrane drug transport proteins are highlighted and include such examples as the association of neurotoxicity with efavirenz, nephrotoxicity with tenofovir, hepatotoxicity with nevirapine, and hyperbilirubinemia with indinavir and atazanavir. Mechanisms of drug resistance conferred by specific viral mutations are also reviewed, with particular attention to replicative viral fitness and transmitted HIV drug resistance with the objectives of providing a better understanding of mechanisms involved in HIV drug resistance and helping health care providers to better manage interpatient variability in drug efficacy and toxicity.

  20. Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria

    Science.gov (United States)

    Meloni, Seema T.; Chang, Charlotte A.; Eisen, Geoffrey; Jolayemi, Toyin; Banigbe, Bolanle; Okonkwo, Prosper I.; Kanki, Phyllis J.

    2016-01-01

    Background While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. Methods We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. Results Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients

  1. CD4 lymphocyte response following anti-retroviral therapy in HIV/AIDS patients - A study in Osmania General Hospital

    OpenAIRE

    Srinivasa Rao Nanyam; Ravala Siddeswari; Budithi Sudarsi; Barla Suryanarayana; Challagali Prabhu Kumar; Thatikala Abhilash

    2016-01-01

    The present study aims serial four year assessment of CD4 cell response after initiation of anti-retroviral therapy (ART) in patients with HIV/AIDS attending Osmania General Hospital, Hyderabad. It was a retrospective hospital based observational study. We included 110 HIV/AIDS who were on ART. Data was collected over a period of 04 years from 2005 to 2008 in the ART Centre, Upgraded Department of General Medicine, Osmania General Hospital. Data regarding CD4 cell count over 4 years was asse...

  2. First-line antiretroviral drug discontinuations in children

    Science.gov (United States)

    Fortuin-de Smidt, Melony; de Waal, Reneé; Cohen, Karen; Technau, Karl-Günter; Stinson, Kathryn; Maartens, Gary; Boulle, Andrew; Igumbor, Ehimario U.; Davies, Mary-Ann

    2017-01-01

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

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

    NARCIS (Netherlands)

    Mugavero, M.J.; May, M.; Harris, R.; Saag, M.S.; Costagliola, D.; Egger, M.; Phillips, A.; Gunthard, H.F.; Dabis, F.; Hogg, R.; Wolf, F. de; Fatkenheuer, G.; Gill, M.J.; Justice, A.; Monforte, A. D'Arminio; Lampe, F.; Miro, J.M.; Staszewski, S.; Sterne, J.A.

    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-naive patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between Jan

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

    DEFF Research Database (Denmark)

    NN, NN; Mugavero, Michael J; May, Margaret

    2008-01-01

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

  5. Absolute lymphocyte count is not a suitable alternative to CD4 count for determining initiation of antiretroviral therapy in fiji.

    Science.gov (United States)

    Balak, Dashika A; Bissell, Karen; Roseveare, Christine; Ram, Sharan; Devi, Rachel R; Graham, Stephen M

    2014-01-01

    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/mm(3). 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/mm(3) or 500 cells/mm(3). 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/mm(3) and if used as a surrogate for a CD4 of ≤500 cells/mm(3) 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.

  6. 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.

  7. 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...... to the other drug class and established cardiovascular risk factors (excluding lipid levels), the relative rate of myocardial infarction per year of protease-inhibitor exposure was 1.16 (95% confidence interval [CI], 1.10 to 1.23), whereas the relative rate per year of exposure to nonnucleoside reverse......-transcriptase inhibitors was 1.05 (95% CI, 0.98 to 1.13). Adjustment for serum lipid levels further reduced the effect of exposure to each drug class to 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93 to 1.09), respectively. CONCLUSIONS: Increased exposure to protease inhibitors is associated with an increased risk...

  8. Bridging the gap between antiretroviral access and adherence in Mexico.

    Science.gov (United States)

    Campero, Lourdes; Herrera, Cristina; Kendall, Tamil; Caballero, Marta

    2007-05-01

    The goal in this article is to examine social problems associated with highly active antiretroviral therapy (HAART) adherence in Mexico and the related challenges for Mexican persons living with HIV/AIDS (PLWHAs). The study was conducted from the perspective of infected and affected individuals. The authors completed 64 in-depth interviews with heterosexual male and female PLWHAs, as well as with some key individuals from their social network. Following the principles of grounded theory, they carried out inductive analysis to create codes and organize central themes. The authors identified problems related to accessing HAART and found that conditions for implementing recommendations made in the international literature to improve adherence are poor. The findings highlight the importance of social factors, such as health care system irregularities, ineffective physician-patient communication, and availability of family and other sources of social support such as self-help groups for PLWHAs' access and adherence to antiretroviral therapy in Mexico.

  9. 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...

  10. 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...

  11. Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.

    Science.gov (United States)

    Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano

    2014-10-01

    HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies.

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

    Science.gov (United States)

    Peluso, Michael J; Spudich, Serena

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  14. Unmasking histoplasmosis immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral therapy

    Science.gov (United States)

    Nabeta, Henry W; Okia, Richard; Rhein, Joshua; Lukande, Robert

    2016-01-01

    Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution. After 2 weeks of amphotericin B and itraconazole therapy, the scheduled treatment involved fluconazole maintenance therapy, which resulted in an improvement of his skin lesions. PMID:28210571

  15. 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.

  16. Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era.

    Science.gov (United States)

    Brickman, Cristina; Palefsky, Joel M

    2015-03-01

    Human papillomavirus (HPV) infection is associated with essentially all cervical cancers, 80-90 % of anal cancers, and a high proportion of oropharyngeal, vaginal, penile, and vulvar cancers. Malignancy is preceded by the development of precancerous lesions termed high-grade squamous intraepithelial lesions (HSIL). Men and women with human immunodeficiency virus (HIV) infection are at high risk of HPV-related malignancies. The incidence of anal cancer in particular has markedly risen during the antiretroviral era due to the increased longevity of patients with HIV and the absence of anal malignancy screening programs. HIV infection may facilitate initial HPV infection by disrupting epithelial cell tight junctions. Once infection is established, HIV may promote HSIL development via the up-regulation of HPV oncogene expression and impairment of the immune response needed to clear the lesion. HIV-infected women should be screened for cervical HSIL and cancer, and HIV-infected men and women should be considered for anal screening programs.

  17. Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

    Science.gov (United States)

    Jordan, M R; Obeng-Aduasare, Y; Sheehan, H; Hong, S Y; Terrin, N; Duong, D V; Trung, N V; Wanke, C; Kinh, N V; Tang, A M

    2014-08-01

    The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.

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

    Science.gov (United States)

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

    2015-08-01

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

  19. 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

  20. Short Communication: Transmitted HIV Drug Resistance in Antiretroviral-Naive Pregnant Women in North Central Nigeria

    Science.gov (United States)

    Sagay, Atiene S.; Chaplin, Beth; Chebu, Philippe; Musa, Jonah; Okpokwu, Jonathan; Hamel, Donald J.; Pam, Ishaya C.; Agbaji, Oche; Samuels, Jay; Meloni, Seema; Sankale, Jean-Louis; Okonkwo, Prosper; Kanki, Phyllis

    2014-01-01

    Abstract The World Health Organization (WHO) recommends periodic surveillance of transmitted drug resistance (TDR) in communities in which antiretroviral therapy (ART) has been scaled-up for greater than 3 years. We conducted a survey of TDR mutations among newly detected HIV-infected antiretroviral (ARV)-naive pregnant women. From May 2010 to March 2012, 38 ARV-naive pregnant women were recruited in three hospitals in Jos, Plateau state, north central Nigeria. Eligible subjects were recruited using a modified version of the binomial sequential sampling technique recommended by WHO. HIV-1 genotyping was performed and HIV-1 drug resistance mutations were characterized according to the WHO 2009 surveillance drug resistance mutation (SDRM) list. HIV subtypes were determined by phylogenetic analysis. The women's median age was 25.5 years; the median CD4+ cell count was 317 cells/μl and the median viral load of 16 was 261 copies/ml. Of the 38 samples tested, 34 (89%) were successfully genotyped. The SDRM rate was <5% for all ART drug classes, with 1/34 (2.9%) for NRTIs/NNRTIs and none for protease inhibitors 0/31 (0%). The specific SDRMs detected were M41L for nucleoside reverse transcriptase inhibitors (NRTIs) and G190A for nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 subtypes detected were CRF02_AG (38.2%), G′ (41.2%), G (14.7%), CRF06-CPX (2.9%), and a unique AG recombinant form (2.9%). The single ARV-native pregnant woman with SDRMs was infected with HIV-1 subtype G′. Access to ART has been available in the Jos area for over 8 years. The prevalence of TDR lower than 5% suggests proper ART administration, although continued surveillance is warranted. PMID:24164431

  1. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy

    Science.gov (United States)

    Rizzardi, G. Paolo; Harari, Alexandre; Capiluppi, Brunella; Tambussi, Giuseppe; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Chave, Jean-Philippe; Lazzarin, Adriano; Pantaleo, Giuseppe

    2002-01-01

    Primary HIV-1 infection causes extensive immune activation, during which CD4+ T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4+ T cell levels, both in terms of percentage and absolute numbers. The increase in CD4+ T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8+ or CD4+ T cell responses. At week 48, the proportion of IFN-γ–secreting CD4+ and CD4+CCR7– T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection. PMID:11877476

  2. 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.

  3. 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

  4. 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...

  5. Highly active antiretroviral therapy per se decreased mortality and morbidity of advanced human immunodeficiency virus disease in Hong Kong

    Institute of Scientific and Technical Information of China (English)

    CHAN Chi-wai; CHENG Lai-sim; CHAN Wai-kit; WONG Ka-hing

    2005-01-01

    Background Morbidity and mortality of advanced human immunodeficiency virus infection (HIV) have declined in Western industrialized countries since the availability of highly active antiretroviral therapy (HAART). It is unclear if this has also happened in Hong Kong.Methods We studied a retrospective cohort of patients with advanced HIV disease in Hong Kong, China. First, the mortality of advanced HIV disease per year was calculated for the decade 1993 to 2002, both annually and according to patient observation before and after 1997. Second, the event rates were estimated for the clinical end points of acquired immune deficiency syndrome (AIDS) and death. Univariate and multivariate analyses were then performed to identify associated factors. Results The crude mortality of advanced HIV disease declined from 10.8-30.4 per 100 patients during 1993-1996, to 0.8-6.9 per 100 patients during 1997-2002. A rate ratio of 4.04 (95% CI, 2.52-6.47) was evident for those observed in 1993-1996, compared to those in 1997-2002. In a multivariate analysis where calendar period was adjusted, use of highly active antiretroviral therapy was associated with rate ratios of 0.13 (95% CI, 0.05-0.33) for death after AIDS, 0.08 (95% CI, 0.04-0.19) for AIDS after a CD4 cell count <200/μl, and 0.21 (95% CI, 0.07-0.67) for death after CD4 cell count <200/μl. In the same analysis, calendar period ceased to be a significant factor after adjustment for use of HAART.Conclusions The mortality and morbidity of advanced human immunodeficiency virus disease have declined in Hong Kong. This improved prognosis was attributable to the use of highly active antiretroviral therapy.

  6. Strategies for Living with the Challenges of HIV and Antiretroviral Use in Zambia

    Science.gov (United States)

    Jones, Deborah; Zulu, Isaac; Mumbi, Miriam; Chitalu, Ndashi; Vamos, Szonja; Gomez, Jacqueline; Weiss, Stephen M.

    2009-01-01

    This study sought to identify strategies for living with the challenges of HIV and antiretroviral (ARV) use among new medication users in urban Zambia. Participants (n = 160) were recruited from urban Lusaka, Zambia. Qualitative Data was drawn from monthly ARV treatment education intervention groups addressing HIV and antiretroviral use. Themes…

  7. Adherence to national guidelines for initiation of antiretroviral regimens in HIV patients: a Danish nationwide study

    DEFF Research Database (Denmark)

    Petersen, Tonny; Andersen, Stig E; Gerstoft, Jan;

    2011-01-01

    To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients.......To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients....

  8. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents.

    NARCIS (Netherlands)

    Beukel, C. van den; Koopmans, P.P.; Ven, A.J.A.M. van der; Smet, P.A.G.M. de; Burger, D.M.

    2006-01-01

    Herbal medicines are widely used by HIV patients. Several herbal medicines have been shown to interact with antiretroviral drugs, which might lead to drug failure. We have aimed to provide an overview of the modulating effects of Western and African herbal medicines on antiretroviral drug-metabolizi

  9. 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...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  11. Is there a role for generic antiretroviral drugs in the United States?

    Science.gov (United States)

    Wormser, Gary P; Lappas, Thomas

    2014-08-01

    The high cost of antiretroviral drugs has limited access to treatment for some HIV-infected patients in the United States and strained public resources. With the introduction of much cheaper generic versions of some of these agents, and with more to come in the next few years, the need increases to define the role of generic antiretroviral drugs in patient management.

  12. 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.

  13. 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.

  14. 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

  15. Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    F.R. Machado

    2006-01-01

    Full Text Available The objective of the present study was to evaluate the duodenal mucosa of HIV-infected patients during antiretroviral therapy. This was an observational study conducted on HIV-positive patients and a control group. Group 1 comprised 22 HIV-negative individuals while 38 HIV-positive individuals were classified according to the CDC 1993 classification into group 2 (A1 or A2 or group 3 (B2, A3, B3, C2, C3. All subjects were submitted to upper gastrointestinal endoscopy with duodenal biopsies. Qualitative, semi-quantitative and quantitative histological analyses were performed. Results were considered significant when P < 0.05. A higher prevalence of inflammatory infiltrate and eosinophilia was observed in the HIV group, together with a reduction in mucosal CD4+ lymphocyte (L counts [median (lower-upper quartiles, 12.82 (8.30-20.33, 6.36 (1.75-11.66 and 1.75 (0.87-3.14 in groups 1, 2 and 3, respectively] which was not correlated with disease stage. The extent of CD4+L count reduction was similar in blood and duodenal mucosa. Normal CD8+L and CD45RO+L counts, and normal numbers of macrophages and antigen-presenting cells were also found in the HIV patients. The cytokine pattern did not differ among groups. Tissue HIV, assessed by p24 antigen, correlated with a higher CD45RO+L count (77.0 (61-79.8 and 43.6 (31.7-62.8 in p24+ and p24-, respectively, P = 0.003, and IL-4 positivity (100 and 48.2% in p24+ and p24-, respectively, P = 0.005. The duodenal mucosa of HIV+ patients showed a relatively preserved histological architecture. This finding may be characteristic of a population without opportunistic infections and treated with potent antiretroviral therapy, with a better preservation of the immune status.

  16. Central nervous system HIV infection in "less-drug regimen" antiretroviral therapy simplification strategies.

    Science.gov (United States)

    Ferretti, Francesca; Gianotti, Nicola; Lazzarin, Adriano; Cinque, Paola

    2014-02-01

    Less-drug regimens (LDR) refer to combinations of either two antiretroviral drugs or ritonavir-boosted protease inhibitor (PI) monotherapy. They may represent a simplification strategy in patients with persistently suppressed human immunodeficiency virus (HIV) viremia, with the main benefits of reducing drug-related toxicities and costs. Systemic virological efficacy of LDR is slightly lower as compared with combined antiretroviral therapy (cART), but patients with failure do not usually develop drug resistance and resuppress HIV replication after reintensification. A major concern of LDR is the lower efficacy in the virus reservoirs, especially in the central nervous system (CNS), where viral compartmentalization and independent evolution of infection may lead to CNS viral escape, often associated with neurologic symptoms. The authors reviewed studies of virological and functional CNS efficacy of LDR, particularly of boosted PI monotherapy regimens, for which more information is available. Symptomatic viral CSF escape was observed mainly in PI/r monotherapy patients with plasma failure and low nadir CD4+ cell counts, and resolved upon reintroduction of triple drug cART, whereas asymptomatic viral failure in CSF was not significantly more frequent in patients on PI/r monotherapy compared with patients on standard cART. In addition, there was no difference in functional outcomes between PI monotherapy and cART patients, irrespective of CSF viral escape. More data are needed on the CNS effect of dual ART regimens and, in general, on long-term efficacy of LDR. Simplification with LDR may be an attractive option in patients with suppressed viral load, if they are well selected and monitored for potential CNS complications.

  17. Genotoxic and Cytotoxic Effects of Antiretroviral Combinations in Mice Bone Marrow

    Science.gov (United States)

    2016-01-01

    Commonly used guidelines for the management of human immunodeficiency virus (HIV) infection (highly active antiretroviral therapy, HAART) include drug combinations such as tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) and combivir [zidovudine (AZT) + 3TC] + efavirenz (EFV). These combinations may enhance the genotoxic effects induced by such drugs individually, since the therapy requires lifelong adherence and the drugs have unknown effects during treatment. Thus, the evaluation of the benefits and risks of HAART is of great importance. In order to assess the cytotoxic and genotoxic potential of three concentrations of each of the antiretroviral combinations TDF + 3TC (800 + 400, 1600 + 800, and 3200 + 1600 mg/kg body weight, BW) and combivir + EFV (200 + 100 + 400, 400 + 200 + 800, and 800 + 400 + 1600 mg/kg BW) after two exposure periods (24 h and 48 h), in the present study the in vivo comet assay (single-cell gel electrophoresis) and the mouse bone marrow micronucleus test were used. Neither TDF + 3TC nor combivir + EFV induced DNA damage at any concentrations tested after 24 h or 48 h using the comet assay. After 24 h, both combinations increased the micronucleus frequency at all concentrations tested. After 48 h, combivir + EFV increased the micronucleated polychromatic erythrocyte (MNPCE) frequency at the two highest concentrations tested. Polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was high for both combinations, suggesting that they can be mitogenic. Since genotoxicity may be related to carcinogenesis, it is necessary to conduct further studies to verify the long-term mutagenic effects of these drugs. PMID:27806085

  18. 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.

  19. Impact of Early Initiation of Antiretroviral Therapy in Patients with Acute HIV Infection in Vienna, Austria.

    Directory of Open Access Journals (Sweden)

    Sandra Herout

    Full Text Available It is unclear whether antiretroviral therapy (ART should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART.We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A or not (group B after diagnosis.Among the 84 individuals with acute HIV infection, 57 (68% received ART within 3 months (A whereas 27 (32% did not receive ART within 3 months (B, respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A when compared to (B (P = 0.002. After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A, when compared to (B (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001. Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004.Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits.

  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. Sclerosing cholangitis by cytomegalovirus in highly active antiretroviral therapy era

    Directory of Open Access Journals (Sweden)

    Carmen Hidalgo-Tenorio

    2013-10-01

    Full Text Available Sclerosing colangitis (SC due to cytomegalovirus (CMV is very rare. It has been described mainly in immunocompromised patients. Currently, in HIV infected patients it is exceptional. The most of cases belong to pre-highly active antiretroviral therapy (pre-HAART and those cases were in stage AIDS with less than 100 CD4/μl. The most frequently involved pathogen in pre-HAART period was Cryptosporidium parvum (30-57% and CMV (10-30%; in late HAART period this information are unaware. CMV has been implicated as a possible etiological agent in primary SC partly because of the ability to cause liver damage and its relationship with smooth muscle antibodies. The most effective treatment for SC was the combination of antiretroviral therapy and endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement. Following, we present the first case of late HAART period which describes a SC extrahepatic without papillary stenosis with CMV as the only cause and clinical presentation of HIV infection in a woman with 177 CD4/μl.

  3. Drug-drug interactions: antiretroviral drugs and recreational drugs.

    Science.gov (United States)

    Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.

  4. Intellectual property rights, market competition and access to affordable antiretrovirals.

    Science.gov (United States)

    Pascual, Fernando

    2014-01-01

    The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact.

  5. [Positioning of lopinavir/ritonavir in antiretroviral treatment schemes].

    Science.gov (United States)

    Camacho, Ángela; Rivero, Antonio

    2014-11-01

    Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission.

  6. Negotiation Strategies for Antiretroviral Drug Purchasers in the United States.

    Science.gov (United States)

    Linnemayr, Sebastian; Ryan, Gery W; Karir, Veena; Liu, Jenny; Palar, Kartika

    2012-01-01

    Antiretroviral treatment has transformed HIV from a death sentence to a chronic condition, allowing people with HIV to live longer and healthier lives. However, they face significant barriers to accessing and affording life-saving-but expensive-antiretroviral (ARV) medications. These barriers are particularly severe for low-income patients, and they disproportionately affect racial and ethnic minorities. High ARV prices create pressure for government insurers to contain costs either by rationing care or by restricting eligibility for public programs. Limited funding, coupled with a growing demand for HIV care and treatment, is likely to make programmatic decisions about who is covered become more difficult over time. Therefore, it is important to identify options for reducing the cost of providing ARVs to allow more people to receive treatment. This study examines a variety of options for negotiating lower ARV procurement costs in U.S. markets. A case-study approach is used to assess options that different stakeholders could use in negotiating ARV price discounts with drug manufacturers given the regulatory and market constraints that exist in the United States.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-04-01

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

  10. Incidence of cervical disease associated to HPV in human immunodeficiency infected women under highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Mogtomo Martin

    2009-06-01

    Full Text Available Abstract Background Women infected with human immunodeficiency virus (HIV may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV, HIV infection and Highly Active Antiretroviral Therapy (HAART on the development of Squamous Intraepithelial lesions (SILs. Out of the 70 HIV infected women from Douala -Cameroon (Central Africa that we included in the study, half (35 were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL. Results Assessment was done according to current antiretroviral regimens available nationwide and CD4 count. It was revealed that 44.3% of HIV-infected women had normal cytology. The overall prevalence of LSIL and HSIL associated to HPV in the studied groups was 24.3% (17/70 and 31.4% (22/70 respectively. Among the 22 HSIL-positive women, 63.6% (14/22 were not on antiretroviral therapy, while 36.4% (8/22 were under HAART. HIV infected women under HAART with positive HSIL, showed a median CD4+ T cell count of 253.7 +/- 31.7 higher than those without therapy (164.7 +/- 26.1. The incidence of HSIL related to HPV infection within the study group independently of HAART initiation was high. Conclusion These results suggest the need for extension and expansion of the current study in order to evaluate the incidence of HPV infection and cervical cancer among HIV-infected and non HIV- infected women in Cameroon.

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

    Directory of Open Access Journals (Sweden)

    Vasan Ashwin

    2009-08-01

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

  12. Three different patterns of CD4 recovery in a cohort of Chinese HIV patients following antiretroviral therapy - a five-year observational study.

    Science.gov (United States)

    Naftalin, Claire M; Wong, Ngai Sze; Chan, Denise P C; Wong, Ka Hing; Reidpath, Daniel D; Lee, Shui Shan

    2015-10-01

    To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.

  13. 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

    (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......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...

  14. 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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Krentz, Hartmut B; Gill, M John

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mathilde Ghislain

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  20. Distal sensory polyneuropathy in human immunodeficiency virus patients and nucleoside analogue antiretroviral agents

    Directory of Open Access Journals (Sweden)

    Jose Jimmy

    2007-01-01

    Full Text Available Distal sensory polyneuropathy, which occur commonly in human immunodeficiency virus (HIV patients can occur as a consequence of the disease itself or the antiretroviral treatment the patient is receiving. Among the antiretroviral agents, nucleoside analogues are commonly associated with neuropathy and the main underlying mechanism is thought to be the mitochondrial toxicity exhibited by these agents. Clinical presentation of antiretroviral induced neuropathy is similar to that associated with the HIV infection and in many patients they may overlap. Treatment is primarily symptomatic and certain pathogenesis-based approaches have shown promising results.

  1. 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...... delay. Design: Randomised controlled trial. Setting: Three public ART facilities in Jimma, Oromia region, Ethiopia. Participants: Adults with HIV eligible for ART with body mass index (BMI) >16. Intervention: Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either...... and CD3 and CD8 counts. Results: Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Anand Moodley

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Kimberly N. Capers

    2011-01-01

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

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

    Science.gov (United States)

    do Lago, Regina Ferro; Costa, Nilson do Rosário

    2010-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu

    2016-01-01

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

  7. Treatment outcomes in a decentralized antiretroviral therapy program: a comparison of two levels of care in north central Nigeria.

    Science.gov (United States)

    Okonkwo, Prosper; Sagay, Atiene S; Agaba, Patricia A; Yohanna, Stephen; Agbaji, Oche O; Imade, Godwin E; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A; Idoko, John A; Kanki, Phyllis J

    2014-01-01

    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care.

  8. Novel antiretroviral drugs and renal function monitoring of HIV patients.

    Science.gov (United States)

    Maggi, Paolo; Montinaro, Vincenzo; Mussini, Cristina; Di Biagio, Antonio; Bellagamba, Rita; Bonfanti, Paolo; Calza, Leonardo; Cherubini, Chiara; Corsi, Paola; Gargiulo, Miriam; Montella, Francesco; Rusconi, Stefano

    2014-01-01

    Chronic kidney disease is a major comorbidity in patients affected by HIV infection. In addition, the introduction of new antiretroviral agents that interact with creatinine transporters is raising some concerns. In this review we analyze the currently available data about three new antiretroviral drugs and one new pharmacokinetic enhancer. Three of them (rilpivirine, cobicistat, dolutegravir) have shown some interactions with renal function, while tenofovir alafenamide fumarate reduces the plasmatic concentration of the parent drug. The future use of tenofovir alafenamide seems to be encouraging in order to reduce the renal interaction of tenofovir. Rilpivirine, cobicistat, and dolutegravir reduce the tubular secretion of creatinine, inducing a decrease of estimated glomerular filtration rate according to creatinine. Rilpivirine and dolutegravir block the uptake of creatinine from the blood, inhibiting organic cation transporter 2, and cobicistat interacts with the efflux inhibiting multidrug and toxin extrusion protein 1. This effect can then be considered a "reset" of the estimated glomerular filtration rate according to creatinine. However, clinicians should carefully monitor renal function in order to identify possible alterations suggestive of a true renal functional impairment. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimation of glomerular filtration rate would be desirable. However, at the moment, other methods of direct glomerular filtration rate measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate glomerular filtration rate is still recommended. Also, tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid.

  9. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.

    Science.gov (United States)

    Ferrari, Luiz F; Levine, Jon D

    2010-09-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.

  10. Antiretroviral therapy outcomes among adolescents and youth in rural Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Helen Bygrave

    Full Text Available Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents 15.1-19 years (adolescents, 19.1-24 years (young adults and 24.1-29.9 years (older adults. Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008. Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35. Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52. This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.

  11. 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.

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

    Science.gov (United States)

    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.

  13. HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

    Science.gov (United States)

    Morse, Caryn G.; Voss, Joachim G.; Rakocevic, Goran; McLaughlin, Mary; Vinton, Carol L.; Huber, Charles; Hu, Xiaojun; Yang, Jun; Huang, Da Wei; Logun, Carolea; Danner, Robert L.; Rangel, Zoila G.; Munson, Peter J.; Orenstein, Jan M.; Rushing, Elisabeth J.; Lempicki, Richard A.; Dalakas, Marinos C.; Kovacs, Joseph A.

    2012-01-01

    Background. Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. Methods. Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)–based ART, and HIV-negative controls. Results. The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+/HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. Conclusions. HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART. PMID:22476717

  14. In vitro-in vivo Pharmacokinetic correlation model for quality assurance of antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Ricardo Rojas Gómez

    2015-10-01

    Full Text Available Introduction: The in vitro-in vivo pharmacokinetic correlation models (IVIVC are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process. Objective: To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans. Methods: Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated. Results: The cumulative areas under the curve (AUC obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model. Conclusions: The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance. 

  15. 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.

  16. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.

    Science.gov (United States)

    Butler, Scott L; Valdez, Hernan; Westby, Michael; Perros, Manos; June, Carl H; Jacobson, Jeffrey M; Levy, Yves; Cooper, David A; Douek, Daniel; Lederman, Michael M; Tebas, Pablo

    2011-11-01

    Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Adjudicated morbidity and mortality outcomes by age among individuals with HIV infection on suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Christopher J Miller

    Full Text Available BACKGROUND: Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts. METHODS: With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4 adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4+ cell count ≥300 cells/mm³ who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS. RESULTS: Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall, 3.6% (<40, 8.7% (40-49 and 16.1% (≥50, respectively (p<0.001. In addition to age, smoking and higher levels of interleukin-6 and D-dimer were significant predictors of the composite outcome. The composite outcome was dominated by serious non-AIDS events (overall 65% of 277 participants with a composite event. Most serious non-AIDS events were due to cardiovascular disease and non-AIDS cancers. CONCLUSIONS: To date, few large studies have carefully collected data on serious non-AIDS outcomes. Thus, reliable estimates of event rates are scarce. Data cited here, from a geographically diverse cohort, will be useful for planning studies of interventions aimed at reducing rates of serious non-AIDS events among people with HIV.

  19. Tuberculosis after one year of combination antiretroviral therapy in Nigeria: a retrospective cohort study.

    Science.gov (United States)

    Akanbi, Maxwell O; Achenbach, Chad J; Feinglass, Joe; Taiwo, Babafemi; Onu, Adamu; Pho, Mai T; Agbaji, Oche; Kanki, Phyllis; Murphy, Robert L

    2013-06-01

    Our objective was to determine tuberculosis (TB) incidence and evaluate TB risk in adults after one or more years of use of combination antiretroviral therapy (cART) through a retrospective cohort study in Jos, Nigeria. We studied a cohort of HIV-infected adults treated with ART for at least 1 year. Based on immunologic and virologic responses to ART, patients were categorized into four groups: CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level ≤400 copies/ml (group 1), CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level >400 copies/ml (group 2), CD4 T cell count 400 copies/ml (group 4). Time to incident TB for the four groups was analyzed using the Kaplan-Meier method. Cox regression models were used to evaluate predictors of incident TB. In this cohort of 5,093 HIV-infected adults, of which 68.4% were female, with a mean age 35.1 years (standard deviation 9.1 years), we observed 98 cases of incident TB during 4 years and 3 months of follow-up. The overall TB incidence rate was 8.7 cases/1,000 patient-years of follow-up. Adjusted hazards for incident TB were 2.11 (95% CI 0.97-4.61), 2.05 (95% CI 1.10-3.79), and 3.65 (95% CI 1.15-5.06) in group 2, 3, and 4 patients, respectively, compared to group 1. Tuberculosis incidence in patients on ART is driven by poor immunologic and/or virologic response. Optimization of HIV treatment should be prioritized to reduce the burden of TB in this high-risk population.

  20. Use of non-antiretroviral drugs among individuals with and without HIV-infection

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Kronborg, Gitte; Larsen, Carsten S

    2017-01-01

    no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non-antiretroviral drugs. Data were analyzed according......AIM: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population. METHODS: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported...... to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes. RESULTS: We identified 4,928 HIV-infected individuals (median...

  1. Impact of switching antiretroviral therapy on lipodystrophy and other metabolic complications: a review

    DEFF Research Database (Denmark)

    Hansen, Birgitte R; Haugaard, Steen B; Iversen, Johan;

    2004-01-01

    Following the introduction of highly active antiretroviral therapy (HAART), metabolic and morphological complications known as HIV associated lipodystrophy syndrome (HALS) have been increasingly common. The approaches to target these complications span from resistance exercise, diet and use...

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Anne Cecile Zoung-Kanyi

    2008-07-01

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

  4. Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment.

    Science.gov (United States)

    Ruíz-López, Patricia; Moreno-Coutiño, Gabriela; Fernández-Martínez, Ramón; Espinoza-Hernández, Jessica; Rodríguez-Zulueta, Patricia; Reyes-Terán, Gustavo

    2015-09-01

    Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ≤450 cel μl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.

  5. Failure of highly active antiretroviral therapy in reconstituting immune response to Clostridium tetani vaccine in aged AIDS patients.

    Science.gov (United States)

    Andrade, Regis M; Andrade, Arnaldo F B; Lazaro, Marta A; Vieira, Morgana M M; Barros, Priscila O; Borner, Alice R S; Silva-Filho, Renato G; Santos, Juliana O; Brindeiro, Rodrigo M; Tanuri, Amilcar; Bento, Cleonice A M

    2010-05-01

    The purpose of this study was to evaluate the impact of age on tetanus-specific immune response in successfully highly active antiretroviral therapy-treated AIDS patients, using healthy age-matched individuals as controls. Whole Peripheral blood mononuclear cells or CD8(+) cell-depleted peripheral blood mononuclear cells from previously tetanus toxoid (TT)-immunized individuals were activated with TT plus IL-2, and cell proliferation, cytokine production, and in vitro HIV-1 replication were measured. The in vivo magnitude of the humoral immune response was also assessed by antibody measurements. Our results showed that, compared with other groups, both in vitro TT-specific lymphoproliferation and serum antibody concentration were lower in older AIDS patients. Although the IL-1beta and tumour necrosis factor alpha (TNF-alpha) production were higher in cultures from aged HIV-1-infected patients, a dramatic damage on the interferon gamma (IFN-gamma) release was observed, when compared with younger patients. CD8(+) T lymphocytes depletion reduced IL-1beta and TNF-alpha release in the older groups, however, it did not significantly alter their IFN-gamma production. Furthermore, the neutralization of endogenous IL-10 did not change the IFN-gamma deficiency in older AIDS patients. Finally, the lower cellular immune response in this patient group was not related to in vitro HIV-1 replication. The results suggest that successfully highly active antiretroviral therapy-treated aged AIDS patients do not reconstitute the immune response to TT, making them probably more susceptible to tetanus even after vaccination.

  6. 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.

  7. Antiretroviral drug supply challenges in the era of scaling up ART in Malawi

    OpenAIRE

    2011-01-01

    Abstract The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This sy...

  8. Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

    Science.gov (United States)

    Jiménez-Montero, Beatriz; Beceiro, José; de José-Gómez, M Isabel; González-Tomé, M Isabel; Gurbindo-Gutierrez, Dolores; Martínez-Pérez, Jorge; Mellado-Peña, M José; Navarro-Gómez, M Luisa; Roa-Francia, Miguel A; Rojo-Conejo, Pablo; Saavedra-Lozano, Jesús; Jiménez de Ory, Santiago; Ramos-Amador, José T

    2014-10-01

    We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

  9. Associations of HIV infection with insulin and glucose levels in antiretroviral-naïve Rwandan women: a cross-sectional analysis

    Science.gov (United States)

    Dusingize, Jean Claude; Hoover, Donald R; Shi, Qiuhu; Mutimura, Eugene; Kiefer, Elizabeth; Anastos, Kathryn

    2013-01-01

    Objectives The purpose of these analyses was to determine the associations of HIV infection and related immune dysfunction with a glucose homeostasis in the population of antiretroviral-naïve HIV-infected and uninfected Rwandan women. We hypothesise that insulin resistance and its consequences in the developing countries may be further elevated with HIV infection itself regardless of antiretroviral therapy. Study design Cross-sectional analysis of a longitudinal cohort. Setting Community-based women's associations. Participants In 2005, 710 HIV-infected (HIV positive) antiretroviral naïve and 226 HIV-uninfected (HIV negative) women were enrolled in the Rwanda Women's Interassociation Study and Assessment (RWISA). Clinical and demographic parameters, CD4 count, fasting insulin and glucose levels, anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were obtained. Linear models were fit to log-transformed Homeostasis Model Assessment (HOMA) with results exponentiated back to a multiplicative effect on the original scale. Primary outcome measures The outcome, insulin resistance, was measured by the HOMA, calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)⁄22.5. Results In adjusted models, HIV-positive women were less insulin resistant than HIV-negative; an HIV-positive woman tended to have 0.728 times as much (95% CI 0.681 to 0.861) HOMA than a comparable HIV-negative woman. Among the HIV-positive women, those with CD4 350 cells/µL. The older age was independently associated with a lower HOMA insulin resistance. After adjusting for body mass index, fat and fat-free mass were not independently associated with HOMA. Conclusions This study found that HIV infection and more advanced HIV infection (CD4 counts <200 cells/µL) were associated with greater insulin sensitivity in antiretroviral naïve African women. These findings provide baseline information for the interpretation of future studies on the effect of antiretroviral therapy on

  10. Effect of antiretroviral therapy on malaria incidence in HIV-infected Ugandan adults

    Science.gov (United States)

    Kasirye, Ronnie P.; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy

    2017-01-01

    Introduction: Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria. Methods: During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4+ at least 250 cells/μl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell. CD4+ cell counts were done 6-monthly. Malaria was defined as fever with a positive blood slide. ART regimens were categorized as nucleoside reverse transcriptase inhibitor (NRTI) only, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or protease inhibitor containing. Malaria incidence was calculated using random effects Poisson regression to account for clustering of events. Results: Malaria incidence in the three ART regimen groups was 9.9 (3.6-27.4), 9.3 (8.3-10.4), and 3.5 (1.6-7.6) per 100 person-years, respectively. Incidence on protease inhibitors was lower than that on the other regimens with the results just reaching significance (adjusted rate ratio 0.4, 95% confidence interval = 0.2–1.0, comparing with NNRTI regimens). Stratification by CTX/placebo use gave similar results, without evidence of an interaction between the effects of CTX/placebo use and ART regimen. There was no evidence of an interaction between ART regimen and CD4+ cell count. Conclusion: There was some evidence that protease inhibitor-containing ART regimens may be associated with a lower clinical malaria incidence compared with other regimens. This effect was not modified by CTX use or CD4+ cell count. The antimalarial properties of protease inhibitors may have clinical and public health importance. PMID:28121670

  11. CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Rosanna W Peeling

    Full Text Available Measurement of CD4+ T-lymphocytes (CD4 is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART. A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration.Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts 350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained.A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.

  12. CD4 Enumeration Technologies: A Systematic Review of Test Performance for Determining Eligibility for Antiretroviral Therapy

    Science.gov (United States)

    Peeling, Rosanna W.; Sollis, Kimberly A.; Glover, Sarah; Crowe, Suzanne M.; Landay, Alan L.; Cheng, Ben; Barnett, David; Denny, Thomas N.; Spira, Thomas J.; Stevens, Wendy S.; Crowley, Siobhan; Essajee, Shaffiq; Vitoria, Marco; Ford, Nathan

    2015-01-01

    Background Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Methods and Findings Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts 350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. Conclusions A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed. PMID:25790185

  13. Clinical outcomes and immune reconstitution in 103 advanced AIDS patients undergoing 12-month highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    DAI Yi; QIU Zhi-feng; LI Tai-sheng; HAN Yang; ZUO Ling-yan; XIE Jing; MA Xiao-jun; LIU Zheng-yin; WANG Ai-xia

    2006-01-01

    Background Highly active antiretroviral therapy (HAART) roduces profound suppression of HIV replication, substantial increase in CD4+ T cells, and partial reconstitution of the immune system. However, the numbers of subjects were small in previous Chinese studies. This study evaluated the efficacy and side effects of HAART in Chinese advanced AIDS patients.Methods One hundred and three antiretroviral drug naive AIDS patients were enrolled in this study and were divided into two groups by their baseline CD4+ count: <100 cells/ μl or ≥ 100 cells/μl. Clinical, virological and immunological outcomes were monitored at baseline and at 1, 3, 6, 9 and 12 months during the course of treatment with HAART.Results One patient died and another was lost from the follow-up. For the remaining 101 HIV/AIDS patients at the 12th month during the HAART, the plasma viral load (VL) was reduced to (3.2±0.7) lg copies/ml, the CD4+ count increased to (168±51) cells/μl [among which the naive phenotype (CD45RA+CD62L+) increased to (49±27) cells/μl and the memory phenotype (CD45RA ̄) increased to (119±55) cells/μl], and the percentage of CD4+CD28+ cells increased. At the same time, there was a significant reduction of CD8+ T cell activation. In the 69 patients with the baseline CD4+ count <100 cells/μl, 37 had a VL <50 copies/ml; while in the 34 patients with the baseline CD4+ count ≥ 100 cells/μl, 25 had a VL <50 copies/ml, the difference between the two groups was statistically significant. The CD4+ T cell count showed a two-phase increase during HAART and a significant positive correlation was shown between the change of CD4+ count and plasma VL. Over 12 months of HAART,10 patients had gastrointestinal side effects, 13 peripheral neuritis, 7 hepatic lesions, 8 hematological side effects,8 skin rashes, 10 lipodystrophy and 1 renal calculus.Conclusions Immune reconstitution as well as the significantly improved clinical outcomes is observed in Chinese advanced AIDS

  14. Incidence and predictors of first line antiretroviral regimen modification in western Kenya.

    Directory of Open Access Journals (Sweden)

    Seth Inzaule

    Full Text Available BACKGROUND: Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya. METHODS: cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling. RESULTS: Over a median follow-up period of 10.7 months, 178 (18.7% patients modified regimens (incidence rate (IR; 18.6 per 100 person years [95% CI: 16.2-21.8]. Toxicity was the most common cited reason (66.3%. In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25-2.66, stavudine (d4T use (aHR; 2.21 95%CI: 1.49-3.30 and increase in age (aHR; 1.02, 95%CI: 1.0-1.04 were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT and tenofovir (TDF use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38-0.96 and aHR; 0.51 95%CI: 0.29-0.91 respectively. Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25-6.05, baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14-5.26, increase in age (aHR; 1.05 95%CI: 1.02-1.07 and high baseline weight >60kg aHR; 2.69 95% CI: 1.58-4.59 were associated with risk of cART modification. CONCLUSIONS: Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. CD4 eligibility thresholds: an analysis of the time to antiretroviral treatment in West African HIV-1 seroconverters

    Science.gov (United States)

    Minga, Albert; Lewden, Charlotte; Gabillard, Delphine; Bomisso, Germain; Toni, Thomas-d’Aquin; Emième, Arlette; Yapo, Vincent; Inwoley, André; Salamon, Roger; Anglaret, Xavier

    2013-01-01

    Background WHO recommends initiating combination antiretroviral treatment (ART) at the minimal threshold of 350 CD4 cells/mm3. In sub-Saharan Africa, the time for a recently infected patient to reach this threshold is unclear. Method We estimated the probability of reaching different CD4 thresholds over time in the ANRS 1220 cohort of HIV-1 seroconverters in Côte d’Ivoire. CD4 slopes were estimated using a mixed linear model. Probabilities of crossing the 350 and 500 CD4 cells/mm3 thresholds were estimated by the Kaplan-Meier method. Results Between 1997 and 2009, 304 recent seroconverters have been enrolled in the Primo-CI cohort (62% men, median baseline age 29 years, median time since the estimated date of seroconversion 9 months). The probability of having a first CD4 count below 500/mm3 was 0.57, 0.72, 0.79 and 0.84 at study entry, 2, 4 and 6 years, respectively. For a first CD4 count below 350/mm3, these figures were 0.29, 0.40, 0.55 and 0.67. The time for 75% of patients to reach the threshold was 3.0 years for 500 CD4/mm3 and 7.0 years for 350 CD4/mm3. Conclusion Almost one third of recent seroconverters had a CD4 count below the current ART eligibility threshold at first contact, about 6% more crossed it each subsequent year, and 25% remained above this threshold after 7 years. If the threshold was raised to 500 cells/mm3, 57% of recent seroconverters would immediately be eligible, while 14% would remain above the threshold at 7 years. These results should help modelers and treatment providers anticipate the need in antiretroviral drugs. PMID:21412060

  18. Quality of life of people living with HIV/AIDS and on highly active antiretroviral therapy in Ethiopia.

    Science.gov (United States)

    Abera, Kebede; Gedif, Teferi; Engidawork, Ephrem; Gebre-Mariam, Tsige

    2010-04-01

    The Amharic version of the Short Form-36 Health Survey (SF-36) was used to measure quality of life among patients on highly active antiretroviral therapy (HAART) at selected governmental hospitals in central and southern Ethiopia. The study was cross-sectional and used SF-36-specific software for automatic scoring of the form's scales and dimensions. Pearson bivariate correlations showed moderate correlation between the SF-36 scales, ranging from 0.2673 between 'general health' and 'vitality,' to 0.8583 between 'role physical' and 'role emotional.' Cronbach's-αwas >0.70 for six out of eight multi-item scales, with values ranging from 0.6500 to 0.8860 for all scales, thus indicating good internal reliability of the Amharic version of the SF-36. The independent variables shown to positively affect mean scores were: duration of treatment, CD4 cell count, and adherence to doses of antiretrovirals. Participants treated for >12 months had higher mean scores for all domains than those who had been treated for ≤12 months. Likewise, those with a CD4 cell count >200 cells/mm(3) had better mean scores for all scales except 'social functioning' and 'mental health' than those with counts ≤200. Participants adhering to treatment (in the last 15 days, according to self-report) had better mean scores for all scales except 'role physical,' 'bodily pain' and 'vitality' in comparison to those who were not adherent. The findings suggest that the Amharic version of the SF-36 is a valid and reliable health survey instrument for use in Ethiopia to assess the quality of life of people living with HIV/AIDS on HAART.

  19. A Pilot Study Assessing the Safety and Latency-Reversing Activity of Disulfiram in HIV-1–Infected Adults on Antiretroviral Therapy

    Science.gov (United States)

    Spivak, Adam M.; Andrade, Adriana; Eisele, Evelyn; Hoh, Rebecca; Bacchetti, Peter; Bumpus, Namandjé N.; Emad, Fatemeh; Buckheit, Robert; McCance-Katz, Elinore F.; Lai, Jun; Kennedy, Margene; Chander, Geetanjali; Siliciano, Robert F.; Siliciano, Janet D.; Deeks, Steven G.

    2014-01-01

    Background. Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4+ T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4+ T cells at concentrations achieved in vivo. Methods. We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1–infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4+ T cells. Results. Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). Conclusions. Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug. PMID:24336828

  20. Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy.

    Science.gov (United States)

    Dauchy, Frédéric-Antoine; Lawson-Ayayi, Sylvie; de La Faille, Renaud; Bonnet, Fabrice; Rigothier, Claire; Mehsen, Nadia; Miremont-Salamé, Ghada; Cazanave, Charles; Greib, Carine; Dabis, Francois; Dupon, Michel

    2011-08-01

    Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.

  1. Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Ferretti Francesca

    2011-12-01

    Full Text Available Abstract Background Rhodococcus equi (R.equi is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART. Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection.

  2. Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy

    DEFF Research Database (Denmark)

    Kjær, Andreas; Kristoffersen, U S; Kofoed, K;

    2009-01-01

    OBJECTIVES: Antiretroviral therapy (ART) in HIV-infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART....... METHODS: In 115 HIV-positive treatment-naïve patients, plasma lipids, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue-type plasminogen activator inhibitor 1 (tPAI-1) and high-sensitivity C-reactive protein (hsCRP) were measured...... before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean+/-standard error of the mean. RESULTS: Prior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296+/-24 vs. 144+/-12 ng/mL), tPAI-1 (18 473+/-1399 vs. 5490+/-576 pg/mL) and hs...

  3. The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.

    Science.gov (United States)

    Kumarasamy, N

    2016-04-01

    Four million people of the global total of 35 million with HIV infection are from South-East Asia. ART is currently utilized by 15 million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.

  4. Food insecurity and antiretroviral adherence among HIV positive adults who drink alcohol.

    Science.gov (United States)

    Kalichman, Seth C; Grebler, Tamar; Amaral, Christina M; McKerney, Megan; White, Denise; Kalichman, Moira O; Cherry, Chauncey; Eaton, Lisa

    2014-10-01

    Food insecurity is associated with HIV treatment non-adherence and poor health outcomes for people living with HIV/AIDS. Given the poor nutritional status common to people who drink alcohol, food insecurity may be particularly problematic for HIV positive individuals who drink alcohol. To examine food insecurity among HIV positive men and women who drink alcohol and its association with antiretroviral therapy (ART) adherence, health outcomes and health service utilization. Adults living with HIV (N = 183) in Atlanta, Georgia who reported alcohol use in the previous week and were receiving ART participated in a 12-month cohort. Participants were recruited from infectious disease clinics and social services to complete computerized interviews, monthly-unannounced pill counts to monitor ART adherence, and daily cell-phone delivered interactive-text assessments for alcohol use. Forty-three percent of participants experienced food insecurity during at least one month of the study period. Food insecurity was independently associated with suboptimal ART adherence and less suppressed HIV viral load over. Individuals who experienced food insecurity also had histories of more medical and psychiatric hospitalizations, and greater mental health problems. Food insecurity is prevalent among alcohol using people receiving ART and food insecurity is associated with treatment non-adherence, poor health outcomes, and increased medical and psychiatric hospitalizations.

  5. Combination antiretroviral therapy and chronic HIV infection affect serum retinoid concentrations: longitudinal and cross-sectional assessments

    Directory of Open Access Journals (Sweden)

    Loignon Maude

    2012-02-01

    Full Text Available Abstract Background Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites, retinoic acids-RAs play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART-related events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo serum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and laboratory abnormalities reported in HIV-infected patients receiving cART. Methods The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIV-infected adults (group1 = G1: twice while on optimal cART (first, during long-term and second, during short term cART and twice during 2 cART interruptions when HIV viral load (VL was detectable. Retinoid concentrations during optimal long term cART in G1 were compared with cross-sectional results from 12 patients (G2 with suboptimal cART (detectable VL and from 28 healthy adults (G3. Serum retinoids were measured by HPLC with ultraviolet detection. Retinoid concentrations were correlated with VL, CD4+ T- cell count and percentages, CD8+38+ fluorescence, triglycerides, cholesterol and C-peptide serum levels. Results During optimal cART, G1 participants had drastically reduced RAs (0.5 ± 0.3 μg/dL; P + T- cell count, CD8+38+ fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01. Conclusions Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly decreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid concentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and immune processes and be responsible for some adverse events observed in HIV-infected persons treated with antiretrovirals. Further studies should assess

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

    Directory of Open Access Journals (Sweden)

    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

  7. Randomized Trial of Central Nervous System–Targeted Antiretrovirals for HIV-Associated Neurocognitive Disorder

    Science.gov (United States)

    Ellis, Ronald J.; Letendre, Scott; Vaida, Florin; Haubrich, Richard; Heaton, Robert K.; Sacktor, Ned; Clifford, David B.; Best, Brookie M.; May, Susanne; Umlauf, Anya; Cherner, Mariana; Sanders, Chelsea; Ballard, Craig; Simpson, David M.; Jay, Cheryl; McCutchan, J. Allen

    2014-01-01

    Background. Antiretroviral (ARV) medications differentially penetrate across the blood-brain barrier into central nervous system (CNS) tissues, potentially influencing their effectiveness in treating brain infection. Methods. This randomized controlled clinical trial (RCT) called for 120 participants at 5 study sites to be randomized 1:1 to CNS-targeted (CNS-T) or non–CNS-T ART. Entry clinical factors such as ARV experience were balanced across arms using an adaptive randomization approach. The primary outcome, change in neurocognitive performance, was measured as the difference in global deficit score (GDS) from baseline to week 16. Results. The study was terminated early on the recommendation of its data safety monitoring board on the basis of slow accrual and a low likelihood of detecting a difference in the primary outcome. No safety concerns were identified. Of 326 participants screened, 59 met entry criteria and were randomized. The primary intent-to-treat analysis included 49 participants who completed week 16. These comprised 39 men and 10 women with a mean age of 44 years (SD, 10 years), and median nadir and current CD4+ T-cell counts of 175 cells/µL and 242 cells/µL, respectively. The proportional improvement in GDS from baseline was nonsignificantly larger (7%; 95% confidence interval [CI], −31% to 62%) in the CNS-T arm than in the non-CNS-T arm, representing a treatment effect size of 0.09 (95% CI, −.48 to .65). Prespecified secondary analysis showed a trend interaction (P = .087), indicating that participants who had baseline plasma virologic suppression may have benefited from CNS-T. Conclusions. This study found no evidence of neurocognitive benefit for a CNS-T strategy in HIV-associated neurocognitive disorders. A benefit for a subgroup or small overall benefits could not be excluded. Clinical Trials Registration NCT00624195. PMID:24352352

  8. Effect of combination antiretroviral therapy on Chinese rhesus macaques of simian immunodeficiency virus infection.

    Science.gov (United States)

    Ling, Binhua; Rogers, Linda; Johnson, Ann-Marie; Piatak, Michael; Lifson, Jeffrey; Veazey, Ronald S

    2013-11-01

    Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to CCR5(+)CD4(+) mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

  9. Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study.

    Science.gov (United States)

    Wandeler, Gilles; Gsponer, Thomas; Bihl, Florian; Bernasconi, Enos; Cavassini, Matthias; Kovari, Helen; Schmid, Patrick; Battegay, Manuel; Calmy, Alexandra; Egger, Matthias; Furrer, Hansjakob; Rauch, Andri

    2013-11-01

    Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients worldwide. It is unclear whether HIV-related outcomes are affected by HBV coinfection. We compared virological suppression and immunological recovery during antiretroviral therapy (ART) of patients of different HBV serological status in the Swiss HIV Cohort Study. CD4 cell recovery during ART was significantly impaired in hepatitis B surface antigen-positive patients and in those with anti-hepatitis B core antigen alone compared with HBV-uninfected patients, despite similar virological efficacy of ART. CD4 increase in patients with resolved HBV infection was similar to that in HBV-uninfected individuals.

  10. The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV Genome Load in HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    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.

  11. 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...

  12. 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

    2015-01-01

    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...... on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. RESULTS: For ART use to result in an incidence of close to 1/1000 person-years requires...... the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men...

  13. Etiology and pharmacologic management of noninfectious diarrhea in HIV-infected individuals in the highly active antiretroviral therapy era.

    Science.gov (United States)

    MacArthur, Rodger D; DuPont, Herbert L

    2012-09-01

    Diarrhea remains a common problem for patients with human immunodeficiency virus (HIV) infection despite highly active antiretroviral therapies (HAART) and can negatively affect patient quality of life and lead to discontinuation or switching of HAART regimens. In the era of HAART, diarrhea from opportunistic infections is uncommon, and HIV-associated diarrhea often has noninfectious causes, including HAART-related adverse events and HIV enteropathy. Diarrhea associated with HAART is typically caused by protease inhibitors (eg, ritonavir), which may damage the intestinal epithelial barrier (leaky-flux diarrhea) and/or alter chloride ion secretion (secretory diarrhea). HIV enteropathy may result from direct effects of HIV on gastrointestinal tract cells and on the gastrointestinal immune system and gut-associated lymphoid tissue, which may be active sites of HIV infection and ongoing inflammation and mucosal damage. New therapies targeting the pathogenic mechanisms of noninfectious diarrheas are needed.

  14. 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...... is linked to inflammation in untreated as well as HAART-treated HIV-1-infected patients....

  15. 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...... 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 patients who are severely affected. In this review, we discuss research relating to pathogenesis, the range of clinical manifestations, treatment options and prevention issues....

  16. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance.

    Science.gov (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E

    2013-01-01

    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  17. An information system to manage the rollout of the antiretroviral treatment programme in the Free State

    Directory of Open Access Journals (Sweden)

    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.

  18. Population uptake of antiretroviral treatment through primary care in rural South Africa

    Directory of Open Access Journals (Sweden)

    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

  19. An information system to manage the rollout of the antiretroviral treatment programme in the Free State.

    Science.gov (United States)

    Kotzé, J E; McDonald, T

    2010-06-01

    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.

  20. HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area

    Directory of Open Access Journals (Sweden)

    Inés Zapiola

    2016-12-01

    Full Text Available The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014. A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6% were treatment-naïve and 59 (43.4% were antiretroviral-experienced patients either with current (n: 24 or previous (n = 35 antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2% women presented at least one resistance associated mutation: 25/94 (26.5% in 2008-2011 and 12/42 (28.5% in 2012-2014 (p > 0.05. Among naïves, 15 (19.5% had at least one mutation: 10/49 (20.4% in the period 2008-2011 and 5/28 (17.8% in 2012-2014 (p > 0.05. The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3% had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina

  1. Antiretroviral treatment induced catatonia in 16-year-old boy

    Directory of Open Access Journals (Sweden)

    Anand Lingeswaran

    2014-01-01

    Full Text Available We present a 16-year-old boy, who had presented to us with catatonic features of mutism, withdrawal, passive negativism, grimacing, gesturing, echopraxia, and excitement of 5 days duration while taking antiretroviral therapy (ART for a period of 2 years. He had history of birth asphyxia and acquired HIV infection from his father when the same syringe and needle was used on both of them in a medical setting where the father and son had consulted for treatment of pyrexia of unknown origin. He was the eldest of a three children family in which the biologic father had acquired HIV through extramarital sexual contact with HIV-infected sex workers but was unaware of his HIV positive status till our patient, the 16-year-old was admitted and treated for pulmonary tuberculosis at 14 years of age. The boy′s mother had only acquired HIV after having three children with the HIV-positive husband, thus leaving the other two children HIV negative. The catatonia completely resolved within 2 days after the ART was withheld, and risperidone 1 mg twice a day was prescribed. This case highlights the risks of ART and breach of universal precautions.

  2. Common mental health problems and antiretroviral therapy adherence.

    Science.gov (United States)

    Nel, Adriaan; Kagee, Ashraf

    2011-11-01

    This paper reviews the literature on various mental health problems and their impact on adherence to antiretroviral therapy (ART). Depression, anxiety disorders, and disorders related to substance abuse were identified as key role-players influencing adherence. The severity of symptoms related to these disorders was found to be inversely related to ART adherence, with the possible exception of post-traumatic stress disorder (PTSD). PTSD was found to have both positive and negative implications for adherence, with severity of symptoms ranging from health-protective concern to disabling distress. Possible solutions aimed at addressing the adverse effects of mental health problems on adherence are discussed. Routine screening in ART settings is suggested in settings where follow-up of positive screen scores are possible, along with the necessary interventions to resolve the disorder of concern. Suggested interventions include utilising psychotherapeutic treatment, both in isolation and in conjunction with medication, to address mental health problems. Furthermore, finding effective ways of marshalling social support is recommended for ensuring optimal adherence, and possibly mitigating the adverse effects of mental health problems. Further research is needed to find feasible ways of identifying, assessing and treating patients with mental health problems in resource-constrained settings where HIV prevalence is highest.

  3. Oropharyngeal Candidiasis in the Era of Antiretroviral Therapy

    Science.gov (United States)

    Thompson, George R.; Patel, Payal K.; Kirkpatrick, William R.; Westbrook, Steven D.; Berg, Deborah; Erlandsen, Josh; Redding, Spencer W.; Patterson, Thomas F.

    2009-01-01

    Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida spp. may also cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of oropharyngeal candidiasis but few studies have evaluated the current impact of ART on the epidemiology of oropharyngeal candidiasis and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied and symptomatic infection occurred in a third. In addition, resistant yeasts were still common occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, oropharyngeal candidasis remains a significant infection in advanced AIDS even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in oropharyngeal candidiasis are important in managing patients with this infection and are the focus of this review. PMID:20156694

  4. Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania

    Directory of Open Access Journals (Sweden)

    Gundersen Svein G

    2011-07-01

    Full Text Available Abstract Background HIV-associated anemia is common and associated with poor prognosis. However, its response to antiretroviral treatment (ART in rural Africa is poorly understood. Methods HIV-infected adults (≥15 years who enrolled in HIV care at Haydom Lutheran Hospital in northern Tanzania were included in the study. The effect of ART (zidovudine/stavudine + lamivudine + efavirenz/nevirapine on HIV-associated anemia was studied in a subset of patients who were anemic at the time they started ART and had a follow-up hemoglobin measurement 12 months later. Pregnant women were excluded from the study, as were women who had given birth within the past 6 weeks. Anemia was defined as hemoglobin Results At enrollment, mean hemoglobin was 10.3 g/dL, and 649 of 838 patients (77.4% were anemic. Of the anemic patients, 254 (39.1% had microcytosis and hypochromia. Among 102 patients who were anemic at ART initiation and had a follow-up hemoglobin measurement after 12 months, the mean hemoglobin increased by 2.5 g/dL (P Conclusions Most patients had anemia at enrollment, of whom nearly 40% had microcytosis and hypochromia suggestive of iron deficiency. The mean hemoglobin increased significantly in patients who received ART, but one third were still anemic 12 months after ART initiation indicating that additional interventions to treat HIV-associated anemia in rural Africa might be warranted, particularly in patients with microcytosis and those treated with zidovudine.

  5. Analysis of contemporary HIV/AIDS health care costs in Germany: Driving factors and distribution across antiretroviral therapy lines.

    Science.gov (United States)

    Treskova, Marina; Kuhlmann, Alexander; Bogner, Johannes; Hower, Martin; Heiken, Hans; Stellbrink, Hans-Jürgen; Mahlich, Jörg; Schulenburg, Johann-Matthias Graf von der; Stoll, Matthias

    2016-06-01

    To analyze contemporary costs of HIV health care and the cost distribution across lines of combination antiretroviral therapy (cART). To identify variations in expenditures with patient characteristics and to identify main cost determinants. To compute cost ratios between patients with varying characteristics.Empirical data on costs are collected in Germany within a 2-year prospective observational noninterventional multicenter study. The database contains information for 1154 HIV-infected patients from 8 medical centers.Means and standard deviations of the total costs are estimated for each cost fraction and across cART lines and regimens. The costs are regressed against various patient characteristics using a generalized linear model. Relative costs are calculated using the resultant coefficients.The average annual total costs (SD) per patient are &OV0556;22,231.03 (8786.13) with a maximum of &OV0556;83,970. cART medication is the major cost fraction (83.8%) with a mean of &OV0556;18,688.62 (5289.48). The major cost-driving factors are cART regimen, CD4-T cell count, cART drug resistance, and concomitant diseases. Viral load, pathology tests, and demographics have no significant impact. Standard non-nucleoside reverse transcriptase inhibitor-based regimens induce 28% lower total costs compared with standard PI/r regimens. Resistance to 3 or more antiretroviral classes induces a significant increase in costs.HIV treatment in Germany continues to be expensive. Majority of costs are attributable to cART. Main cost determinants are CD4-T cells count, comorbidity, genotypic antiviral resistance, and therapy regimen. Combinations of characteristics associated with higher expenditures enhance the increasing effect on the costs and induce high cost cases.

  6. Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Mqondisi Tshabalala

    Full Text Available The rapid scale-up of highly active antiretroviral therapy (HAART and use of single dose Nevirapine (SD NVP for prevention of mother-to-child transmission (pMTCT have raised fears about the emergence of resistance to the first line antiretroviral drug regimens. A cross-sectional study was conducted to determine the prevalence of primary drug resistance (PDR in a cohort of young (<25 yrs HAART-naïve HIV pregnant women attending antenatal clinics in Chitungwiza, Zimbabwe. Whole blood was collected in EDTA for CD4 counts, viral load, serological estimation of duration of infection using the BED Calypte assay and genotyping for drug resistance. Four hundred and seventy-one women, mean age 21 years; SD: 2.1 were enrolled into the study between 2006 and 2007. Their median CD4 count was 371cells/µL; IQR: 255-511 cells/µL. Two hundred and thirty-six samples were genotyped for drug resistance. Based on the BED assay, 27% were recently infected (RI whilst 73% had long-term infection (LTI. Median CD4 count was higher (p<0.05 in RI than in women with LTI. Only 2 women had drug resistance mutations; protease I85V and reverse transcriptase Y181C. Prevalence of PDR in Chitungwiza, 4 years after commencement of the national ART program remained below WHO threshold limit (5%. Frequency of recent infection BED testing is consistent with high HIV acquisition during pregnancy. With the scale-up of long-term ART programs, maintenance of proper prescribing practices, continuous monitoring of patients and reinforcement of adherence may prevent the acquisition and transmission of PDR.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Differences in HIV Burden and Immune Activation within the Gut of HIV+ Patients on Suppressive Antiretroviral Therapy

    Science.gov (United States)

    Yukl, Steven; Gianella, Sara; Sinclair, Elizabeth; Epling, Lorrie; Li, Qingsheng; Duan, Lijie; Choi, Alex L. M.; Girling, Valerie; Ho, Terence; Li, Peilin; Fujimoto, Katsuya; Lampiris, Harry; Hare, C. Bradley; Pandori, Mark; Haase, Ashley T.; Günthard, Huldrych F.; Fischer, Marek; Shergill, Amandeep; McQuaid, Kenneth; Havlir, Diane V.; Wong, Joseph K.

    2010-01-01

    Background The gut is a major reservoir for HIV in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. Methods In 8 HIV-1+ adults on ART with CD4>200 and plasma VL<40, levels of HIV and T-cell activation were measured in blood and endoscopic biopsies from the duodenum, ileum, right colon, and rectum. Results HIV DNA and RNA per CD4+T-cell were higher in all four gut sites compared to blood. HIV DNA increased from the duodenum to the rectum, while the median HIV RNA peaked in the ileum. HIV DNA correlated positively with T-cell activation in the PBMC but negatively with T-cell activation in the gut. Multiply-spliced RNA was infrequently detected in gut, and unspliced RNA/DNA ratios were lower in the colon and rectum relative to PBMC, reflecting paradoxically low HIV transcription given the higher T-cell activation in the gut. Conclusions HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA and T-cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. PMID:20939732

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints

    Directory of Open Access Journals (Sweden)

    Yiannoutsos Constantin T

    2009-06-01

    Full Text Available Abstract Background Mortality of HIV-infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change. Methods In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV-infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub-Saharan Africa. Results As a first reported data-driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy. Conclusion By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data-driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting.

  11. Impact of a pharmaceutical care program on clinical evolution and antiretroviral treatment adherence: a 5-year study

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Weijun Zhu

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

  13. Antiretroviral treatment program retention among HIV-infected children in the Democratic Republic of Congo.

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy in colonized epithelial multilayer cultures.

    Directory of Open Access Journals (Sweden)

    Richard B Pyles

    Full Text Available There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1. The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral.

  16. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults : 48-week results from the antiretroviral regimen evaluation study (ARES)

    NARCIS (Netherlands)

    Lowe, SH; Wensing, AMJ; Hassink, EAM; ten Kate, RW; Richter, C; Schreij, G; Koopmans, PP; Juttmann, J.; van der Tweel, I.; Lange, JMA; Borleffs, JCC

    2005-01-01

    Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  17. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).

    NARCIS (Netherlands)

    Lowe, S.H.; Wensing, B.M.; Hassink, E.A.M.; Kate, R.W. ten; Richter, C.; Schreij, G.; Koopmans, P.P.; Juttmann, J.R.; Tweel, I. van de; Lange, J.M.A.; Borleffs, J.C.

    2005-01-01

    BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  18. Determining eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte counts, hemoglobin and body mass index

    Directory of Open Access Journals (Sweden)

    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.

  19. Prevalence of Thrombocytopenia among Chinese Adult Antiretroviral-naïve HIV-positive Patients

    Directory of Open Access Journals (Sweden)

    Hong-Wei Fan

    2015-01-01

    Full Text Available Background: The prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults. Methods: We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. Results: A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients 350 cells/mm 3 (2.8% compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1% (P = 0.002 and P = 0.005, respectively. The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001. We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7% versus men who have sex with men (3.9% (P = 0.002 and versus heterosexual transmission (3.9% (P = 0.001. In binary logistic regression analyses, age ≥50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018, 2.091 (95% CI: 1.078, 4.055, P = 0.029 and 2.259 (95% CI: 1.028, 4.962, P = 0.042, respectively. Conclusions: Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years, HCV-Ab positivity and lower CD4

  20. Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda

    Directory of Open Access Journals (Sweden)

    Sempa Joseph

    2012-09-01

    Full Text Available Abstract Background Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART at CD4+ T cell (CD4 count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250–350 cell/μl (early versus Methods Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually. Results Treatment delay varied from 6–18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33–3.10 disability adjusted life years (DALY’s per patient. Lifetime treatment costs were $4,300–$5,248 for early initiation and $3,940–$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260–$270. Conclusions In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

  1. Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding--the Kisumu Breastfeeding Study, Kenya: a clinical trial.

    Directory of Open Access Journals (Sweden)

    Timothy K Thomas

    2011-03-01

    Full Text Available BACKGROUND: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. METHODS AND FINDINGS: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3 were 8.4% (95% confidence interval [CI] 5.8%-12.0% and 4.1% (1.8%-8.8%, respectively (p = 0.06; the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8% and 8.7% (6.1%-12.3%, respectively (p = 0.01. None of the 12 maternal and 51 infant deaths (including two second-born infants were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%. CONCLUSIONS: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These

  2. The HIV antiretroviral drug efavirenz has LSD-like properties.

    Science.gov (United States)

    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

    2013-11-01

    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 indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.

  3. Immune activation in HIV-infected aging women on antiretrovirals--implications for age-associated comorbidities: a cross-sectional pilot study.

    Directory of Open Access Journals (Sweden)

    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.

  4. 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

  5. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Neuhaus, Jacqueline; Duprez, Daniel

    2011-01-01

    Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compa...

  6. Uptake of combination antiretroviral therapy and HIV disease progression according to geographical origin in seroconverters in Europe, Canada, and Australia

    DEFF Research Database (Denmark)

    Jarrin, Inma; Pantazis, Nikos; Gill, M John

    2012-01-01

    We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART).......We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART)....

  7. Provision of antiretroviral treatment in conflict settings: the experience of Médecins Sans Frontières

    Directory of Open Access Journals (Sweden)

    Ellman Tom

    2010-06-01

    Full Text Available Abstract Introduction Many countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed. Methods From 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned. Results In the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145. At analysis, 2645 (64% remained on ART, 422 (10% had died, 466 (11% lost to follow-up, 417 (10% transferred to another programme, and 195 (5% had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3. Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities. Conclusions With commitment, simplified

  8. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.

    Directory of Open Access Journals (Sweden)

    Alejandra Borjabad

    2011-09-01

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing

  9. Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals

    Science.gov (United States)

    Shilaih, Mohaned; Marzel, Alex; Braun, Dominique L.; Scherrer, Alexandra U.; Kovari, Helen; Young, Jim; Calmy, Alexandra; Darling, Katharine; Battegay, Manuel; Hoffmann, Matthias; Bernasconi, Enos; Thurnheer, Maria C.; Günthard, Huldrych F.; Kouyos, Roger D.

    2017-01-01

    Abstract After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2–1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation. PMID:28079818

  10. Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

    Directory of Open Access Journals (Sweden)

    Cheryl A Stoddart

    Full Text Available BACKGROUND: The SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals. METHODOLOGY/PRINCIPAL FINDINGS: Endpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3 as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions. CONCLUSION: Given the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans.

  11. Treatment Outcomes in a Decentralized Antiretroviral Therapy Program: A Comparison of Two Levels of Care in North Central Nigeria

    Directory of Open Access Journals (Sweden)

    Prosper Okonkwo

    2014-01-01

    Full Text Available Background. Decentralization of antiretroviral therapy (ART services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1% were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P<0.001 and 24 weeks (P<0.001 with similar responses at 48 weeks (P=0.11 and higher rates of viral suppression (<400 c/mL at 12 (P<0.001 and 48 weeks (P=0.03, but similar responses at 24 weeks (P=0.21. Mortality was 2.3% versus 5.0% (P<0.001 at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P=0.001 at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

  14. Female gender predicts lower access and adherence to antiretroviral therapy in a setting of free healthcare

    Directory of Open Access Journals (Sweden)

    Hogg Robert S

    2011-04-01

    Full Text Available Abstract Background Barriers to HIV treatment among injection drug users (IDU are a major public health concern. However, there remain few long-term studies investigating key demographic and behavioral factors - and gender differences in particular - that may pose barriers to antiretroviral therapy (ART, especially in settings with universal healthcare. We evaluated access and adherence to ART in a long-term cohort of HIV-positive IDU in a setting where medical care and antiretroviral therapy are provided free of charge through a universal healthcare system. Methods We evaluated baseline antiretroviral use and subsequent adherence to ART among a Canadian cohort of HIV-positive IDU. We used generalized estimating equation logistic regression to evaluate factors associated with 95% adherence to antiretroviral therapy estimated based on prescription refill compliance. Results Between May 1996 and April 2008, 545 IDU participants were followed for a median of 23.8 months (Inter-quartile range: 8.5 - 91.6, among whom 341 (63% were male and 204 (37% were female. Within the six-month period prior to the baseline interview, 133 (39% men and 62 (30% women were on ART (p = 0.042. After adjusting for clinical characteristics as well as drug use patterns measured longitudinally throughout follow-up, female gender was independently associated with a lower likelihood of being 95% adherent to ART (Odds Ratio [OR] = 0.70; 95% Confidence Interval: 0.53-0.93. Conclusions Despite universal access to free HIV treatment and medical care, female IDU were less likely to access and adhere to antiretroviral therapy, a finding that was independent of drug use and clinical characteristics. These data suggest that interventions to improve access to HIV treatment among IDU must be tailored to address unique barriers to antiretroviral therapy faced by female IDU.

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

    Directory of Open Access Journals (Sweden)

    Bailey Kerry A

    2010-08-01

    Full Text Available Abstract Background Antiretroviral treatment services delivered in hospital settings in Africa increasingly lack capacity to meet demand and are difficult to access by patients. We evaluate the effectiveness of nurse led primary care based antiretroviral treatment by comparison with usual hospital care in a typical rural sub Saharan African setting. Methods We undertook a prospective, controlled evaluation of planned service change in Lubombo, Swaziland. Clinically stable adults with a CD4 count > 100 and on antiretroviral treatment for at least four weeks at the district hospital were assigned to either nurse led primary care based antiretroviral treatment care or usual hospital care. Assignment depended on the location of the nearest primary care clinic. The main outcome measures were clinic attendance and patient experience. Results Those receiving primary care based treatment were less likely to miss an appointment compared with those continuing to receive hospital care (RR 0·37, p p = 0·001. Those receiving primary care based, nurse led care were more likely to be satisfied in the ability of staff to manage their condition (RR 1·23, p = 0·003. There was no significant difference in loss to follow-up or other health related outcomes in modified intention to treat analysis. Multilevel, multivariable regression identified little inter-cluster variation. Conclusions Clinic attendance and patient experience are better with nurse led primary care based antiretroviral treatment care than with hospital care; health related outcomes appear equally good. This evidence supports efforts of the WHO to scale-up universal access to antiretroviral treatment in sub Saharan Africa.

  16. Insulin resistance and diabetes mellitus associated with antiretroviral use in HIV-infected patients: pathogenesis, prevention, and treatment options.

    Science.gov (United States)

    Tebas, Pablo

    2008-09-01

    The contribution of current antiretroviral treatment regimens to the long-term survival of HIV-infected individuals is accompanied by increased risk of glucose metabolism abnormalities in this patient population. The risk of insulin resistance and diabetes in HIV-infected patients receiving antiretroviral treatment stems from 2 sources: exposure to the same environmental factors that have led to an increased incidence of these conditions in the general population and the negative effects on glucose metabolism inherent to components of antiretroviral treatment regimens. This article reviews the pathogenesis and diagnosis of insulin resistance and diabetes and the contribution of components of antiretroviral therapy regimens to increased risk for these conditions. Optimization of antiretroviral treatment regimens for HIV-infected patients with or at increased risk for development of abnormalities in glucose metabolism is discussed.

  17. Antiretroviral treatment for HIV infection/AIDS and the risk of developing hyperglycemia and hyperlipidemia Tratamento antiretroviral para a infecção pelo HIV/AIDS e o risco de desenvolver hiperglicemia e dislipidemia

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio Ramos de Araújo

    2007-04-01

    Full Text Available A cross-sectional study with internal comparison groups was conducted to describe sociodemographic characteristics, as well as verify the association between the type of antiretroviral treatment used and hyperglycemia and hyperlipidemia, with special attention to the use of HIV protease inhibitors. The data was obtained through an interview questionnaire, as well as blood and urine samples that were collected for the laboratory exams. A total of 418 patients were interviewed. 46 of these, however, met the exclusion criteria. The sample was therefore composed by 372 HIV positive patients, attended at the laboratory of the Correia Picanço State Hospital for the collection of blood, to estimate the HIV viral load and/or TCD4 cell counts from August to November 2000. The association between the variables was tested using the chi-square test and the p-value. A multiple logistic regression analysis was carried out to adjust for potential confounding factors. A greater frequency of patients with high glucose levels was observed among those making use of antiretroviral therapy without protease inhibitors, but the number of patients limited the comparisons. An association was verified between the total serum cholesterol level and the use of HIV protease inhibitors (p = 0.047 even after controlling for age. An association was also observed between the triglyceride levels and the use of HIV protease inhibitors, which remained after adjustment for age, sex and creatinine levels (p Um estudo epidemiológico transversal, com caráter analítico, foi realizado para descrever características sócio-demográficas bem como verificar a associação entre o tipo de tratamento antiretroviral empregado e hiperglicemia e hiperlipidemia, com especial atenção aos pacientes em uso de inibidores da protease do HIV. As informações foram obtidas a partir de um questionário e da coleta de sangue e urina para a execução dos exames laboratoriais. Foram entrevistados

  18. Delayed onset renal failure in a patient on tenofovir based antiretroviral regimen

    Directory of Open Access Journals (Sweden)

    M Murali Krishna

    2014-01-01

    Full Text Available Tenofovir is recommended as one of the first line agents in combination with other antiretroviral drugs for management of human immunodeficiency virus (HIV. It is known to cause renal failure after exposure for a median duration of 5 months. We report tenofovir induced adverse drug reaction in a 56-year-old female patient who was diagnosed to have HIV 1 infection since 10 years. The combination antiretroviral treatment included tenofovir, emtricitabine and ritonavir/lopinavir regimen since the last 6 years. She presented with recent onset renal failure and renal biopsy showed interstitial nephritis which could probably attributable to tenofovir.

  19. 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 Virologic.......026) and time (P 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

  20. 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......: Virologic response (viral load Virologic.......026) and time (P 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

  1. Access to highly active antiretroviral therapy (HAART) in the WHO European Region 2003-2005

    DEFF Research Database (Denmark)

    Bollerup, Annemarie R; Donoghoe, Martin C; Lazarus, Jeff

    2008-01-01

    To assess changes in access to highly active antiretroviral therapy (HAART) between the end of 2002 and the end of 2005, and to review the capacity for further HAART scale-up in the then 52 Member States of the WHO European Region.......To assess changes in access to highly active antiretroviral therapy (HAART) between the end of 2002 and the end of 2005, and to review the capacity for further HAART scale-up in the then 52 Member States of the WHO European Region....

  2. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Mónica Rodríguez

    2012-01-01

    Full Text Available We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes.

  3. [Central nervous system infections in HIV patients in the era of high activity antiretroviral treatment].

    Science.gov (United States)

    Rivas González, P; Fernández Guerrero, M L

    2005-06-01

    Although the incidence of most central nervous system infections in HIV+ patients has decreased after the introduction of the modern antiretroviral treatments, they are still a major cause of morbidity and mortality. New technologies in molecular biology and neuroradiology establish the diagnosis in many cases and have decreased the need for cerebral biopsy. Prognosis has improved substantially after the introduction of high activity antiretroviral treatment; more active treatments are needed, however, for infections as PML or citomegalovirus encephalitis because of their still unacceptably high mortality.

  4. CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1-infected individuals.

    Science.gov (United States)

    Ahuja, Sunil K; Kulkarni, Hemant; Catano, Gabriel; Agan, Brian K; Camargo, Jose F; He, Weijing; O'Connell, Robert J; Marconi, Vincent C; Delmar, Judith; Eron, Joseph; Clark, Robert A; Frost, Simon; Martin, Jeffrey; Ahuja, Seema S; Deeks, Steven G; Little, Susan; Richman, Douglas; Hecht, Frederick M; Dolan, Matthew J

    2008-04-01

    The basis for the extensive variability seen in the reconstitution of CD4(+) T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at CCR5 genotypes favoring CD4(+) T cell recovery are similar to those that blunted CD4(+) T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4(+) cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution.

  5. Hepatotoxicity and effectiveness of a Nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral hepatitis B or C infection in Cameroon

    Directory of Open Access Journals (Sweden)

    Gwet Henri

    2010-03-01

    Full Text Available Abstract Background Coinfection with hepatitis B virus (HBV or hepatitis C virus (HCV in HIV-infected patients receiving a commonly used nevirapine-based antiretroviral therapy is a major concern for African clinicians owing to its high prevalence, the infrequent testing and treatment of viral hepatitis, and the impact of liver disease on the tolerability and effectiveness of anti-HIV treatment. We compared the hepatotoxicity and the immunological, virological and clinical effectiveness of a nevirapine-based antiretroviral therapy between patients infected with HIV only and patients coinfected with hepatitis B or C virus in Cameroon. Methods A retrospective cohort study was conducted among HIV-1-infected patients. Plasma HBV DNA and HCV RNA were tested in positive or indeterminate samples for HBsAg or HCV antibodies, respectively. All patients received nevirapine and lamivudine plus stavudine or zidovudine. Results Of 169 HIV-1-infected patients with a median baseline CD4 count of 135 cells/mm3 (interquartile range [IQR] 67-218, 21% were coinfected with HBV or HCV. In coinfected patients, the median viral load was 2.47 × 107 IU/mL for HBV (IQR 3680-1.59 × 108 and 928 000 IU/mL for HCV (IQR 178 400-2.06 × 106. Multivariate analyses showed that the risk of hepatotoxicity was 2-fold higher in coinfected patients (p p = 0.8, HIV-1 viral load below 400 copies/mL (p = 0.9, death (p = 0.3 and death or new AIDS-defining event (p = 0.1. Nevirapine was replaced by a protease inhibitor in 4 patients owing to hepatotoxicity. Conclusion This study suggests that the nevirapine-based antiretroviral therapy could be used safely as first-line treatment in patients with low CD4 cell count in Africa despite frequent coinfections with HBV or HCV and infrequent testing of these infections. Although testing for HBV and HCV should be systematically performed before initiating antiretroviral therapy, transaminases elevations at baseline or during treatment should be

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

    Science.gov (United States)

    Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

    2012-01-01

    Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Depression and posttraumatic stress disorder among HIV-infected Gambians on antiretroviral therapy.

    Science.gov (United States)

    Peterson, Kevin; Togun, Toyin; Klis, Sandor; Menten, Joris; Colebunders, Robert

    2012-10-01

    Mood disorders are more frequent among people with HIV infection than among non-HIV-infected individuals of the same age, socioeconomic status, and HIV risks. They have been associated with worse adherence and clinical outcomes, yet remain underdiagnosed and undertreated in sub-Saharan Africa. We explored the relationship between mood disorders using the 10-item depression scale of the Centers for Epidemiological Studies (CES-D10) and the 22-item Impact of Events Scale-Revised (IES-R) for posttraumatic stress disorder, and a range of demographic and HIV-related variables among 252 consecutive subjects on antiretroviral therapy (ART). The study was conducted in the Genito-Urinary Medicine Clinic of the Medical Research Council's Gambia Unit. These screening tests were positive in 7% and 30%, respectively, of the patients, with higher scores (more depression or more post-traumatic stress) associated with female gender, more advanced WHO clinical stage, and lower Karnofsky Perfomance Scale rating. Higher CES-D10 scores were also seen among those on their second ART regimen. No relationship was seen with age, time on ART, viral load, or CD4 cell count. Compared to an earlier study at the same site in subjects prior to starting ART, the prevalence of depression in those stabilized on ART was dramatically reduced (by 34%, from 41%) while that of PTSD dropped less (by 13%, from 43%). Integrating the CES-D10 or a similar instrument into patient preparation for ART is recommended in order to identify those who may benefit from further mental health investigations, specific therapy, or closer follow-up during early ART.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Ana Cecília Montes Gil

    Full Text Available CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART. We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6, A (29, B (78 and C (39. Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN, grade 2 (5.0-9.9 times ULN, grade 3 (10.0-15.0 times ULN and grade 4 (> 15.0 times ULN. To assess hepatotoxicity risk factors, odds ratios (OR and adjusted odds ratios (aOR for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152 patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI, 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85 and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25. No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

  12. Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

    Science.gov (United States)

    Matthews, Lynn T.; Ashaba, Scholastic; Tsai, Alexander C.; Kanters, Steve; Robak, Magdalena; Psaros, Christina; Kabakyenga, Jerome; Boum, Yap; Haberer, Jessica E.; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.

    2014-01-01

    Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18–49 years) initiating ART in rural Uganda (2005–2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0–12 months post-pregnancy outcome), or non–pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27–37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95–245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and “never married” were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non–pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health. PMID:25436816

  13. 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% (p5 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.

  14. Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study.

    Science.gov (United States)

    Carlson, Renee Donahue; Rolfes, Melissa A; Birkenkamp, Kate E; Nakasujja, Noeline; Rajasingham, Radha; Meya, David B; Boulware, David R

    2014-06-01

    Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.

  15. Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

    Science.gov (United States)

    Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin CS; Peter, Aniekan I; Azu, Onyemaechi O

    2016-01-01

    Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof. PMID:27818734

  16. Self-reported adherence to antiretroviral therapy in HIV+ population from Bata, Equatorial Guinea.

    Science.gov (United States)

    Salmanton-García, Jon; Herrador, Zaida; Ruiz-Seco, Pilar; Nzang-Esono, Jesús; Bendomo, Veronica; Bashmakovic, Emma; Nseng-Nchama, Gloria; Benito, Agustín; Aparicio, Pilar

    2016-01-01

    The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives.

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

    Directory of Open Access Journals (Sweden)

    Petropoulos Christos J

    2005-11-01

    Full Text Available Abstract Background Central nervous system (CNS exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1 progression of systemic infection, 2 CSF white blood cell (WBC count, 3 antiretroviral therapy (ART, and 4 neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL. CSF HIV viral loads (VLs correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

  18. Outcomes of antiretroviral therapy in Vietnam: results from a national evaluation.

    Directory of Open Access Journals (Sweden)

    Duc Bui Nguyen

    Full Text Available OBJECTIVES: Vietnam has significantly scaled up its national antiretroviral therapy (ART program since 2005. With the aim of improving Vietnam's national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID. The results of this evaluation may have relevance for other national ART programs with significant PWID populations. DESIGN: Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART. METHODS: Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data. RESULTS: Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4-76.5, median age 30, interquartile range [IQR]: 26-34, 62.0% reported a history of intravenous drug use, CI: 58.6-65.3. Median baseline CD4 cell count was 78 cells/mm(3 (IQR: 30-162 and 30.4% (CI: 25.8-35.1 of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3% or d4T/3TC/EFV (18.6%. Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8-89.9, 84.0% (CI: 81.8-86.0, 78.8% (CI: 75.7-81.6, and 74.6% (CI: 69.6-79.0. Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45-153, 142 (IQR: 78-217, 213 (IQR: 120-329, and 254 (IQR: 135-391 cells/mm(3. Patients who were PWID showed significantly poorer retention. CONCLUSIONS: The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.

  19. Financing equitable access to antiretroviral treatment in South Africa

    Directory of Open Access Journals (Sweden)

    McIntyre Di

    2010-07-01

    Full Text Available Abstract Background While South Africa spends approximately 7.4% of GDP on healthcare, only 43% of these funds are spent in the public system, which is tasked with the provision of care to the majority of the population including a large proportion of those in need of antiretroviral treatment (ART. South Africa is currently debating the introduction of a National Health Insurance (NHI system. Because such a universal health system could mean increased public healthcare funding and improved access to human resources, it could improve the sustainability of ART provision. This paper considers the minimum resources that would be required to achieve the proposed universal health system and contrasts these with the costs of scaled up access to ART between 2010 and 2020. Methods The costs of ART and universal coverage (UC are assessed through multiplying unit costs, utilization and estimates of the population in need during each year of the planning cycle. Costs are from the provider’s perspective reflected in real 2007 prices. Results The annual costs of providing ART increase from US$1 billion in 2010 to US$3.6 billion in 2020. If increases in funding to public healthcare only keep pace with projected real GDP growth, then close to 30% of these resources would be required for ART by 2020. However, an increase in the public healthcare resource envelope from 3.2% to 5%-6% of GDP would be sufficient to finance both ART and other services under a universal system (if based on a largely public sector model and the annual costs of ART would not exceed 15% of the universal health system budget. Conclusions Responding to the HIV-epidemic is one of the many challenges currently facing South Africa. Whether this response becomes a “resource for democracy” or whether it undermines social cohesiveness within poor communities and between rich and poor communities will be partially determined by the steps that are taken during the next ten years. While the

  20. Accessibility of antiretroviral therapy in Ghana: convenience of access.

    Science.gov (United States)

    Addo-Atuah, Joyce; Gourley, Dick; Gourley, Greta; White-Means, Shelley I; Womeodu, Robin J; Faris, Richard J; Addo, Nii Akwei

    2012-01-01

    The convenience of accessing antiretroviral therapy (ART) is important for initial access to care and subsequent adherence to ART. We conducted a qualitative study of people living with HIV/AIDS (PLWHA) and ART healthcare providers in Ghana in 2005. The objective of this study was to explore the participants' perceived convenience of accessing ART by PLWHA in Ghana. The convenience of accessing ART was evaluated from the reported travel and waiting times to receive care, the availability, or otherwise, of special considerations, with respect to the waiting time to receive care, for those PLWHA who were in active employment in the formal sector, the frequency of clinic visits before and after initiating ART, and whether the PLWHA saw the same or different providers at each clinic visit (continuity of care). This qualitative study used in-depth interviews based on Yin's case-study research design to collect data from 20 PLWHA and 24 ART healthcare providers as study participants. • Reported travel time to receive ART services ranged from 2 to 12 h for 30% of the PLWHA. • Waiting time to receive care was from 4 to 9 h. • While known government workers, such as teachers, were attended to earlier in some of the centres, this was not a consistent practice in all the four ART centres studied. • The PLWHA corroborated the providers' description of the procedure for initiating and monitoring ART in Ghana. • PLWHA did not see the same provider every time, but they were assured that this did not compromise the continuity of their care. Our study suggests that convenience of accessing ART is important to both PLWHA and ART healthcare providers, but the participants alluded to other factors, including open provider-patient communication, which might explain the PLWHA's understanding of the constraints under which they were receiving care. The current nation-wide coverage of the ART programme in Ghana, however, calls for the replication of this study to identify

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

    Directory of Open Access Journals (Sweden)

    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

  2. Fixed-dose combination for adults accessing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    SA HIV Clinicians Society

    2013-03-01

    Full Text Available This document serves to guide clinicians and programme managers on how to switch from 3 separate antiretroviral (ARV drugs to the new, single, fixed-dose combination (FDC tablet containing tenofovir (TDF, emtricitabine (FTC and efavirenz (EFV. Summary Transitioning from individual drugs to an FDC tablet needs to be managed carefully, particularly regarding stock management, ordering processes, supply-chain integrity and comprehensive patient counselling. Priority groups • Initially, FDC supply will be insufficient to provide for all FDC-suitable patients • Therefore, the National Department of Health (NDoH has recommended that the following patient groups be prioritized for FDC initiation/switch: • Priority group 1: All HIV-positive patients newly initiating ART – adults, adolescents and pregnant women (regardless of CD4 count (amendment to the guidelines for the prevention of mother-to-child transmission of HIV (PMTCT anticipated in April 2013 – and who do not have contra-indications to the FDC component drugs • Priority group 2: HIV-positive pregnant women and breastfeeding mothers currently stable on lamivudine (3TC, TDF and EFV • Priority group 3: Virologically suppressed patients on a stavudine (d4T-based regimen and who have normal renal function • Priority group 4: Stable patients receiving individual TDF, 3TC and EFV and who have tuberculosis (TB co-infection • Priority group 5: Stable patients receiving individual TDF, 3TC and EFV and who have other co-morbidites (e.g. hypertension, diabetes • Priority group 6: Patients receiving individual TDF, 3TC and EFV and who request to switch to the FDC treatment • Priority group 7: Patients receiving individual TDF, 3TC and EFV and who, after counselling, agree to switch to the FDC treatment. Important: Clinic staff must co-ordinate this process and only switch as many patients to the FDC tablet as stock allows. This should avoid patients being switched back and forth

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Abdu Wakawa Ibrahim

    2014-11-01

    Full Text Available Clinical depression is a highly debilitating illness, which is often under-diagnosed and negatively impacts on the quality of life of its sufferers. When it co-exists with other medical conditions, its effect is even more incapacitating. Undiagnosed depression in the context of HIV infection leads to accelerated decline in CD4+ cell counts with concomitant increase in the viral load and poor adherence to the antiretroviral medications which lead to viral mutation and the evolution of resistant strains. This study examined the prevalence of depression, its correlates and the frequency of the diagnosis of the condition among HIV+ subjects on highly active antiretroviral therapy (HAART by the internists and general physicians at the University of Maiduguri Teaching Hospital in Northeastern Nigeria. Three hundred and fifty representative samples of HIV+ adults on HAART were drawn from the Antiretroviral Therapy Clinic of the Institution. Diagnosis of depression was made using the International Classification of Diseases-10 criteria based on Composite International Diagnostic Interview generated data. Socio-demographic and clinical variables were also analyzed for their correlation with depression in the subjects. About 20% of the respondents were diagnosed with clinical depression and no diagnosis of the condition was hitherto entertained in all the respondents. The independent determinants of depression in the participants were: female gender [odds ratio (OR=3.87 (95% confidence interval, CI: 2.089-7.183], past history of psychiatric illness [OR=43.81 (95% CI: 9.731-197.30] and family history of psychiatric illness in first-degree relatives of the subjects [OR=14.364 (95% CI=5.327- 38.729]. Depression is a relatively common psychiatric condition among adults on HAART, there is therefore the need for routine screening of this condition among HIV+ subjects in order to optimize patient care and improve clinical outcomes.

  7. Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage.

    Science.gov (United States)

    Sanchez, Ana B; Varano, Giuseppe P; de Rozieres, Cyrus M; Maung, Ricky; Catalan, Irene C; Dowling, Cari C; Sejbuk, Natalia E; Hoefer, Melanie M; Kaul, Marcus

    2015-10-19

    HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.

  8. Socioeconomic status and survival of persons with AIDS before and after the introduction of highly active antiretroviral therapy. Lazio AIDS Surveillance Collaborative Group.

    Science.gov (United States)

    Rapiti, E; Porta, D; Forastiere, F; Fusco, D; Perucci, C A

    2000-09-01

    We estimated the AIDS survival by neighborhood socioeconomic status before (1993-1995) and after (1996-1997) the introduction of highly active antiretroviral therapy in Rome, Italy, in a retrospective cohort of persons with AIDS followed through July 31, 1998. Participants included 1,474 persons with AIDS residing in Rome who were diagnosed in 1993-1997. We calculated hazard ratios (HRs) of death for two diagnostic periods (before and after highly active antiretroviral therapy was introduced) by neighborhood socioeconomic status categorized into four levels (level I = highest socioeconomic status), using the Cox model and adjusting for gender, age, intravenous drug use, CD4 cell count at diagnosis, AIDS-defining disease, and hospital of diagnosis. Thirty-four per cent of persons with AIDS (N = 503) had survived as of mid-1998. For persons with AIDS diagnosed in 1993-1995, we found little difference in the risk of death by neighborhood socioeconomic status. For 1996-1997, the risk of death was greater for persons with lower neighborhood socioeconomic status, especially for levels III and IV [HR = 2.81 (95% confidence interval = 1.38-5.76), and HR = 2.55 (95% confidence interval = 1.27-5.14), respectively, compared with level I]. Stratified analyses showed that the greatest difference was found for women and drug users. In conclusion, even in a country with universal health coverage that provides therapy at no cost, differences in survival of persons with AIDS have emerged by neighborhood socioeconomic status since highly active antiretroviral therapy was introduced. Inequalities in health-care access or in medical management, or poor adherence to treatment, could explain the observed heterogeneity.

  9. Ex vivo response to histone deacetylase (HDAC inhibitors of the HIV long terminal repeat (LTR derived from HIV-infected patients on antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Hao K Lu

    Full Text Available Histone deacetylase inhibitors (HDACi can induce human immunodeficiency virus (HIV transcription from the HIV long terminal repeat (LTR. However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+ isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART. We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.

  10. Comparison of single and boosted protease inhibitor versus nonnucleoside reverse transcriptase inhibitor-containing cART regimens in antiretroviral-naïve patients starting cART after January 1, 2000

    DEFF Research Database (Denmark)

    Mocroft, A; Horban, A; Clumeck, N;

    2006-01-01

    BACKGROUND: Few published studies have considered both the short- and long-term virologic or immunologic response to combination antiretroviral therapy (cART) and the impact of different cART strategies. PURPOSE: To compare time to initial virologic (200/mm3 cell...... increase) response in antiretroviral-naïve patients starting either a single protease inhibitor (PI; n = 183), a ritonavir-boosted PI regimen (n = 197), or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART regimen (n = 447) after January 1, 2000, and the odds of lack of virologic...... or immunologic response at 3 years after starting cART. METHOD: Cox proportional hazards models and logistic regression. RESULTS: After adjustment, compared to patients taking an NNRTI-regimen, patients taking a single-PI regimen were significantly less likely to achieve a viral load (VL)

  11. First-line antiretroviral treatment outcome in a patient presenting an HIV-1/2 multiclass drug resistant infection

    Directory of Open Access Journals (Sweden)

    E Castro

    2012-11-01

    Full Text Available Background: With the expansion of HIV-2 epidemic beyond African countries, co-infection with HIV-1 becomes a global challenge. We have recently identified an HIV-1/2 dual infection with both viruses bearing multiclass drug resistance in an untreated patient [1]. We now present the patient's combined antiretroviral treatment (cART outcome after 6 months follow-up. Patient and Methods: Clinical samples were obtained upon informed consent from a 23-year-old man living in Guinea-Bissau until March 2011 when he moved to Switzerland. As previously reported [1], HIV-1/2 co-infection was confirmed by HIV-1 PCR (21.000 copies/ml and total HIV-1/2 viremia (4.351 nU/ml by product-enhanced reverse transcriptase (PERT assay. The patient denied previous HIV testing or exposure to antiretroviral drugs. Dual infection consisted of HIV-1 CRF02_AG bearing resistance mutations M184V/V90I and HIV-2 clade A, harboring K65R/D67N mutations as amplified from proviral-DNA. Baseline CD4 + T-cell count was 408 cell/mm3. We initiated cART in accordance to drug resistance mutations (see below. Treatment compliance was assessed with an electronic pillbox device and drug-plasma concentrations. Clinical and laboratory follow up were done at weeks 2, 4, 9, 12 and 24. Results: cART was initiated with tenofovir/emtricitabine (TDF/FTC, boosted-darunavir (DRV/r and raltegravir(RAL. Treatment compliance was fluctuant during the first 3 months after which it remained stable with an average monthly intake of 92%. Antiretroviral drug-plasma concentrations were traced at percentile 25th. HIV-1 viremia became undetectable at week 12. Additionally, HIV-2 viremia was retrospectively assessed by real-time RT-PCR at two independent laboratories showing undetectable values across the study period including baseline. Thus, baseline viremia, as assessed by the PERT test for particle-associated reverse transcriptase activity was due to HIV-1 alone. CD4 + T-cell count was 559 cell/mm3 at

  12. Dynamics of HIV-1 DNA level in highly antiretroviral-experienced patients receiving raltegravir-based therapy.

    Science.gov (United States)

    Charpentier, C; Piketty, C; Laureillard, D; Tisserand, P; Si-Mohamed, A; Weiss, L; Bélec, L

    2012-02-01

    To assess dynamics of HIV-1 DNA in highly antiretroviral (ARV)-experienced HIV-infected patients successfully treated with raltegravir (RAL)-containing therapy. Nineteen patients with virological failure whose ARV treatment was switched to a RAL-based salvage regimen with virological success were included (Group I). Ten patients in virological failure and responding to ARV salvage therapy not containing RAL were also included (Group II). The HIV-1 DNA level in peripheral blood mononuclear cells (PBMC) was assessed by real-time PCR at baseline, W12, W24, W36 or W48. In group I, a marked decrease in the HIV-1 DNA level was observed at W12 both in PBMC (median decrease = 0.38 log(10)copies/10(6)PBMC; P < 0.001) and in CD4 T cells (0.85 log(10)copies/10(6)CD4 T cells; P < 0.001). Plasma HIV-1 RNA decrease was correlated with HIV-1 DNA decrease expressed as copies/10(6)CD4 T cells (r = 0.55, P = 0.03). HIV-1 DNA level reached a steady state by W24. Thus, RAL-containing treatment in highly ARV-experienced patients was associated with a rapid HIV-1 DNA decrease, mainly in the circulating CD4 T cells compartment. Group II patients showed an early decrease in the HIV-1 DNA load until W12, which was 2.5-fold less pronounced in the CD4 T cells compartment than in the RAL-treated patients. The potent action of RAL-containing treatment observed in the CD4 T cells compartment may suggest a pronounced reduced inhibition in the pool of regenerating CD4 T cells on a RAL-based therapy.

  13. Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality.

    Directory of Open Access Journals (Sweden)

    Martin W G Brinkhof

    2009-04-01

    Full Text Available BACKGROUND: Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa. METHODS AND FINDINGS: Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs with 95% confidence intervals (CIs. Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67% patients were female, and 10,811 of 12,720 patients (85% with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1 per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO stage III/IV, compared to 1.00 (0.55-1.81 per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6 and 3.44 (1.91-6.17. Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94 per 100 person-years and the SMR was 1.14 (0.47-2.77. CONCLUSIONS: Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the

  14. Expenditures for the care of HIV-infected patients in rural areas in China's antiretroviral therapy programs

    Directory of Open Access Journals (Sweden)

    Duan Song

    2011-01-01

    Full Text Available Abstract Background The Chinese government has provided health services to those infected by the human immunodeficiency virus (HIV under the acquired immunodeficiency syndrome (AIDS care policy since 2003. Detailed research on the actual expenditures and costs for providing care to patients with AIDS is needed for future financial planning of AIDS health care services and possible reform of HIV/AIDS-related policy. The purpose of the current study was to determine the actual expenditures and factors influencing costs for untreated AIDS patients in a rural area of China after initiating highly active antiretroviral therapy (HAART under the national Free Care Program (China CARES. Methods A retrospective cohort study was conducted in Yunnan and Shanxi Provinces, where HAART and all medical care are provided free to HIV-positive patients. Health expenditures and costs in the first treatment year were collected from medical records and prescriptions at local hospitals between January and June 2007. Multivariate linear regression was used to determine the factors associated with the actual expenditures in the first antiretroviral (ARV treatment year. Results Five ARV regimens are commonly used in China CARES: zidovudine (AZT + lamivudine (3TC + nevirapine (NVP, stavudine (D4T + 3TC + efavirenz (EFV, D4T + 3TC + NVP, didanosine (DDI + 3TC + NVP and combivir + EFV. The mean annual expenditure per person for ARV medications was US$2,242 (US$1 = 7 Chinese Yuan (CNY among 276 participants. The total costs for treating all adverse drug events (ADEs and opportunistic infections (OIs were US$29,703 and US$23,031, respectively. The expenses for treatment of peripheral neuritis and cytomegalovirus (CMV infections were the highest among those patients with ADEs and OIs, respectively. On the basis of multivariate linear regression, CD4 cell counts (100-199 cells/μL versus P = 0.02; and ≥200 cells/μL versus P P P = 0.04 and OIs (P = 0.02 were significantly

  15. Predictors of immunological failure after initial response to highly active antiretroviral therapy in HIV-1-infected adults: a EuroSIDA study

    DEFF Research Database (Denmark)

    Dragsted, Ulrik Bak; Mocroft, Amanda; Vella, Stefano;

    2004-01-01

    BACKGROUND: Factors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined. OBJECTIVE: Our aim was to investigate predictors of immunological failure after initial CD4(+) response. METHODS: Data were from EuroSIDA, a prospective, international...... diminishes with a longer time receiving treatment and is associated with pretreatment CD4(+) cell count, ongoing viral replication, and intravenous drug use......., observational human immunodeficiency virus (HIV) type 1 cohort. RESULTS: Of 2347 patients with an increase in CD4(+) cell count >or=100 cells/microL within 6-12 months of the initiation of HAART, 550 (23%) subsequently experienced immunological failure (CD4(+) count less than or equal to the pre-HAART value......], 2.05; 95% CI, 1.83-2.31; PHIV-1 risk behavior (P=.047 for a global comparison of risk groups). CONCLUSION: The risk of immunological failure in patients with an immunological response to HAART...

  16. 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.

  17. 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.

  18. Tissue-resident macrophages can contain replication-competent virus in antiretroviral-naive, SIV-infected Asian macaques

    Science.gov (United States)

    DiNapoli, Sarah R.; Ortiz, Alexandra M.; Wu, Fan; Matsuda, Kenta; Hirsch, Vanessa M.; Knox, Kenneth

    2017-01-01

    SIV DNA can be detected in lymphoid tissue–resident macrophages of chronically SIV-infected Asian macaques. These macrophages also contain evidence of recently phagocytosed SIV-infected CD4+ T cells. Here, we examine whether these macrophages contain replication-competent virus, whether viral DNA can be detected in tissue-resident macrophages from antiretroviral (ARV) therapy–treated animals and humans, and how the viral sequences amplified from macrophages and contemporaneous CD4+ T cells compare. In ARV-naive animals, we find that lymphoid tissue–resident macrophages contain replication-competent virus if they also contain viral DNA in ARV-naive Asian macaques. The genetic sequence of the virus within these macrophages is similar to those within CD4+ T cells from the same anatomic sites. In ARV-treated animals, we find that viral DNA can be amplified from lymphoid tissue–resident macrophages of SIV-infected Asian macaques that were treated with ARVs for at least 5 months, but we could not detect replication-competent virus from macrophages of animals treated with ARVs. Finally, we could not detect viral DNA in alveolar macrophages from HIV-infected individuals who received ARVs for 3 years and had undetectable viral loads. These data demonstrate that macrophages can contain replication-competent virus, but may not represent a significant reservoir for HIV in vivo.

  19. Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Salgado Maria

    2011-12-01

    Full Text Available Abstract Background While initiation of highly active antiretroviral therapy (HAART during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Results Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of + T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+ T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+ T cells do not have potent HIV suppressive activity. Conclusion This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL mediated suppression that has been reported in many elite suppressors.

  20. 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...

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

    NARCIS (Netherlands)

    A. Mocroft; O. Kirk; P. Reiss; S. de Wit; D. Sedlacek; M. Beniowski; J. Gatell; A.N. Phillips; B. Ledergerber; J.D. Lundgren

    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 le

  2. Therapeutic drug monitoring: an aid to optimising response to antiretroviral drugs?

    NARCIS (Netherlands)

    Aarnoutse, R.E.; Schapiro, J.M.; Boucher, C.A.B.; Hekster, Y.A.; Burger, D.M.

    2003-01-01

    Therapeutic drug monitoring (TDM) has been proposed as a means to optimise response to highly active antiretroviral therapy (HAART) in HIV infection. Protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine satisfy many criteria for TDM. Nuc

  3. Antiretroviral therapy optimisation without genotype resistance testing: a perspective on treatment history based models

    NARCIS (Netherlands)

    M.C.F. Prosperi; M. Rosen-Zvi; A. Altman; M. Zazzi; S. Di Giambenedetto; R. Kaiser; E. Schülter; D. Struck; P. Sloot; D.A. van de Vijver; A.-M. Vandamme; A. Sönnerborg

    2010-01-01

    Background: Although genotypic resistance testing (GRT) is recommended to guide combination antiretroviral therapy (cART), funding and/or facilities to perform GRT may not be available in low to middle income countries. Since treatment history (TH) impacts response to subsequent therapy, we investig

  4. Predictors and treatment strategies of HIV-related fatigue in the combined antiretroviral therapy era

    NARCIS (Netherlands)

    Jong, Eefje; Oudhoff, Lisanne A.; Epskamp, Cynthia; Wagener, Marlies N.; van Duijn, Miranda; Fischer, Steven; van Gorp, Eric C. M.

    2010-01-01

    Objective To assess predictors and reported treatment strategies of HIV-related fatigue in the combined antiretroviral (cART) era. Method Five databases were searched and reference lists of pertinent articles were checked. Studies published since 1996 on predictors or therapy of HIV-related fatigue

  5. 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...

  6. Detection of lipoatrophy in human immunodeficiency virus-1-infected children treated with highly active antiretroviral therapy.

    NARCIS (Netherlands)

    Hartman, K.; Verweel, G.; Groot, R. de; Hartwig, N.G.

    2006-01-01

    BACKGROUND: Highly active antiretroviral therapy has been associated with lipodystrophy in adults. Much is unknown about its characteristics, especially in children. OBJECTIVE: To obtain an objective case definition of the lipodystrophy syndrome. METHODS: This was a cross-sectional study. One invest

  7. Prevalence of Lipodystrophy in HIV-infected Children in Tanzania on Highly Active Antiretroviral Therapy

    NARCIS (Netherlands)

    Kinabo, G.; Sprengers, M.; Msuya, L.J.; Shayo, A.M.; Asten, H.A.G.H. van; Dolmans, W.M.V.; Ven, A.J.A.M. van der; Warris, A.

    2013-01-01

    OBJECTIVE: : Highly active antiretroviral therapy (HAART) has been associated with lipodystrophy (LD) in adults but data are more limited for children. The purpose of this study was to determine the prevalence of and risk factors for LD in Tanzanian children receiving HAART by clinical assessment an

  8. Facilitators and barriers to antiretroviral therapy adherence among adolescents in Ghana

    NARCIS (Netherlands)

    Ankrah, D.; Koster, E.S.; Teeuwisse, A.K.; Arhinful, D.K.; Agyepong, I.A.; Lartey, Margaret

    2016-01-01

    INTRODUCTION: Adherence to antiretroviral therapy (ART) is known to be challenging among adolescents living with HIV/AIDS, notwithstanding the life-saving importance of this therapy. Of the global total number of adolescents living with HIV in 2013, 83% reside in sub-Saharan Africa. The study aimed

  9. Further research needed to support a policy of antiretroviral therapy as an HIV prevention initiative

    DEFF Research Database (Denmark)

    Rodger, Alison J; Bruun, Tina; Vernazza, Pietro;

    2013-01-01

    The results from the HPTN 052 trial have increased the focus on use of antiretroviral therapy (ART) for prevention of HIV transmission; however, condom use also effectively prevents HIV transmission. Studies in heterosexual serodiscordant couples with viral suppression have so far only reported...

  10. Pharmacoeconomic evaluation of intensified antiretroviral treatment strategies in HIV/AIDS

    NARCIS (Netherlands)

    Bos, J M; Berg, L T; Postma, Maarten

    2001-01-01

    There have been great technological advances in the use of antiretroviral therapies to slow down disease progression in HIV/AIDS. Combinations of therapeutics and the use of several diagnostic methods have resulted in both declines in mortality and the occurrence of opportunistic infections. The hig

  11. 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

  12. Health service delivery models for the provision of antiretroviral therapy in sub-Saharan Africa

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V; Safreed-Harmon, Kelly; Nicholson, Joey

    2014-01-01

    OBJECTIVES: In response to the lack of evidence-based guidance for how to continue scaling up antiretroviral therapy (ART) in ways that make optimal use of limited resources, to assess comparative studies of ART service delivery models implemented in sub-Saharan Africa. METHODS: A systematic lite...

  13. 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.

  14. 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

    BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started...

  15. 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.

  16. Low retention of HIV-infected patients on antiretroviral therapy in 11 clinical centers

    Science.gov (United States)

    Ekouevi, Didier K.; Balestre, Eric; Ba-Gomis, Franck-Olivier; Eholie, Serge Paul; Maiga, Moussa; Amani-Bosse, Clarisse; Minga, Albert; Messou, Eugène; Sow, Papa Salif; Lewden, Charlotte; Traoré, Hamar Allassane; Bissagnene, Emmanuel; Dabis, François

    2010-01-01

    Summary Objective To study factors associated with the probability of retention in antiretroviral therapy (ART) programs in West Africa. Methods The International epidemiologic Databases to Evaluate AIDS (IeDEA) in West Africa is a prospective, operational, observational cohort study based on collaboration between 11 cohorts of HIV-infected adult patients in Benin, Côte d'Ivoire, Gambia, Mali and Senegal. All patients aged 16 and older at ART initiation, with documented gender and date of ART initiation, were included. For those with at least one day of follow-up, Kaplan-Meier method and Weibull regression model were used to estimate the 12-month probability of retention in care and the associated factors. Results 14,352 patients (61% female) on ART were included in this data merger. Median age was 37 years (IQR: 31-44 years) and median CD4 count at baseline was 131 cells/mm3 (IQR: 48-221 cells/mm3). The first line regimen was NNRTI-based for 78% of patients, protease-inhibitor based for 17%, and three NRTIs for 3%. The probability of retention was 0.90 (95% confidence interval [CI]: 0.89-0.90) at 3 months, 0.84 (95%CI: 0.83-0.85) at 6 months and 0.76 (95%CI: 0.75-0.77) at 12 months. The probability of retention in care was lower in patients with baseline CD4 count 200 cells/mm3, in men (aHR=1.17; 95%CI: 1.10-1.24; p=0.0002), in younger patients (<30 years) (aHR=1.10; 95%CI: 1.03-1.19; p=0.01) and in patients with low hemoglobinemia <8g/dL (aHR=1.33; 95%CI: 1.21-1.45; p<0.0001). Availability of funds for systematic tracing was associated with better retention (aHR=0.29; 95%CI: 0.16-0.55; p=0.001). Conclusions Close follow-up, promoting early access to care and ART and a decentralized system of care may improve the retention in care of HIV-patients on ART. PMID:20586958

  17. 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

  18. 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

  19. Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.

    Science.gov (United States)

    Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat

    2015-03-01

    We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients.

  20. Plasma levels of soluble CD27: a simple marker to monitor immune activation during potent antiretroviral therapy in HIV-1-infected subjects

    Science.gov (United States)

    DE MILITO, A; ALEMAN, S; MARENZI, R; SÖNNERBORG, A; FUCHS, D; ZAZZI, M; CHIODI, F

    2002-01-01

    Plasma levels of soluble CD27 (sCD27) are elevated in diseases characterized by T cell activation and are used as a marker of immune activation. We assessed the usefulness of determining plasma sCD27 as a marker for monitoring immune activation in HIV-1-infected patients treated with highly active antiretroviral therapy (HAART). A first cross-sectional examination of 68 HIV-1-infected and 18 normal subjects showed high levels of sCD27 in HIV-1 infection; plasma sCD27 was correlated to HIV-1 viraemia and inversely correlated to CD4+ T cell count. Twenty-six HIV-1-infected patients undergoing HAART were studied at baseline and after 6, 12, 18 and 24 months of therapy. Seven additional patients under HAART were analysed at baseline, during and after interruption of therapy. In the total population, HAART induced a significant and progressive reduction, but not a normalization, of plasma levels of sCD27 after 24 months. A full normalization of plasma sCD27 was observed in the virological responders (undetectable HIV-1 RNA at months 18 and 24) and also in patients with moderate immunodeficiency at baseline (CD4+ T cell count >200 cells/mm3). Changes in plasma neopterin paralleled the changes in sCD27 but only baseline sCD27 levels were predictive of a greater increase in CD4+ T cell count during the follow-up. Discontinuation of therapy resulted in a rapid increase of sCD27 plasma levels associated with viraemia rebound and drop in CD4+ T cell count. Our findings suggest that plasma sCD27 may represent an alternative and simple marker to monitor immune activation during potent antiretroviral therapy. HIV-1-induced immune activation can be normalized by HAART in successfully treated patients where the disease is not advanced. PMID:11966765

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

    Directory of Open Access Journals (Sweden)

    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

  2. Romidepsin-induced HIV-1 viremia during effective antiretroviral therapy contains identical viral sequences with few deleterious mutations

    Science.gov (United States)

    Winckelmann, Anni; Barton, Kirston; Hiener, Bonnie; Schlub, Timothy E.; Shao, Wei; Rasmussen, Thomas A.; Østergaard, Lars; Søgaard, Ole S.; Tolstrup, Martin; Palmer, Sarah

    2017-01-01

    Objective: To investigate the origin of the HIV-1 viremia induced by the latency-reversing agent romidepsin. Design: Six individuals on suppressive antiretroviral therapy received romidepsin administered intravenously once weekly for 3 consecutive weeks. CD4+ T cells were obtained at baseline, following the second and third romidepsin infusion, and 10 weeks after the final romidepsin treatment. Plasma samples were collected 24 and 72 h after romidepsin infusions. Methods: Single-genome sequencing of the env and p24-RT region was used to genetically characterize the virus from proviral DNA, the transcribed cell-associated RNA and the plasma RNA pool. Results: In three of six participants with available plasma samples we identified plasma HIV-1 RNA sequences that were identical to DNA and/or cell-associated RNA sequences from peripheral blood CD4+ T cells. In two participants, plasma RNA sequences contained expansions of identical sequences, corresponding to 62 and 100% of the total sequences, respectively. Plasma HIV-1 RNA had very low amounts of defective viruses compared to cell-associated RNA (odds ratio 20.85, P < 0.001) and to DNA (odds ratio 7.07, P = 0.011) during romidepsin therapy. Conclusions: Romidepsin induced transcription from proviruses in peripheral blood cells, which contributed to viremia in patients on suppressive therapy. The intermingling of these cell-associated HIV-1 RNA with DNA sequences indicates transcription from a diverse range of proviruses, but the expansions of identical viral plasma sequences with few defects indicate that the romidepsin-induced viremia arises from intact proviruses with highly similar or identical genetic backgrounds. PMID:28272134

  3. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Julian H Elliott

    2014-10-01

    Full Text Available Human immunodeficiency virus (HIV persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART. The primary endpoint was change in cell associated unspliced (CA-US HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065. Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90% with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1. CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.ClinicalTrials.gov NCT01365065.

  4. Risk-factors for non-adherence to antiretroviral therapy Fatores preditivos de não-adesão à terapia antiretroviral

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Fraga Silva

    2009-06-01

    Full Text Available Cross-sectional study analyzed as case-control to identify risk factors for non-adherence to antiretroviral therapy. We studied 412 out-clinics HIV infected subjects of three public hospitals of Recife, Pernambuco. The objective was to examine the association between non-adherence to the antiretroviral therapy and biological, social-behavior and demographics and economic factors, factors related to the disease and/or treatment, factors related to life habits and depression symptoms. Variables significantly associated with non-adherence to antiretroviral therapy were: time elapsed since HIV diagnosis (p = 0.002, daily dose (p = 0.046, use of alcohol (p = 0.030 and past drug use (p = 0.048, and borderline p-values were found for educational level (p = 0.093 and family monthly income (p = 0.08. In the multivariable analysis, the factors that remained in the final model were family monthly income, time period with HIV infection and use of alcohol. No association was observed between non-adherence to antiretroviral therapy and gender, age, sexual orientation, marital status, educational level and place of residence. Based on our results and the local situation we suggest: assessment of social needs; training of partners and/or families on supporting adherence, creation of "adherence groups" to motivate and to reassure patients on the benefits of treatment; counseling and/or psychotherapy for alcohol drinkers.Estudo transversal com análise tipo caso-controle, que avaliou 412 pacientes de hospitais públicos do Recife - PE, com o objetivo de identificar fatores preditivos de não adesão à terapia antiretroviral. Verificou-se associação entre não adesão à terapia antiretroviral e aspectos biológicos, sócio-comportamentais e demográficos, econômicos, relacionados à doença e ao tratamento, aos hábitos de vida e aos distúrbios do humor. Variáveis com associação estatisticamente significante com não adesão na análise univariada foram

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

    Directory of Open Access Journals (Sweden)

    Joel Emery

    2010-05-01

    Full Text Available Joel Emery1, Neora Pick2, Edward J Mills3, Curtis L Cooper11The Ottawa Hospital Division of Infectious Diseases, University of Ottawa, Ottawa, Canada; 2Oak Tree Clinic, BC Women’s Hospital, Vancouver, Canada; 3Faculty of Health Sciences, University of Ottawa, Ottawa, CanadaObjective: The influence of biological sex on human immunodeficiency virus (HIV antiretroviral treatment outcome is not well described in HIV–hepatitis C (HCV coinfection.Methods: We assessed patients’ clinical outcomes of HIV–HCV coinfected patients initiating antiretroviral therapy attending the Ottawa Hospital Immunodeficiency Clinic from January 1996 to June 2008.Results: We assessed 144 males and 39 females. Although similar in most baseline characteristics, the CD4 count was higher in females (375 vs 290 cells/μL. Fewer females initiated ritonavir-boosted regimens. The median duration on therapy before interruption or change was longer in males (10 versus 4 months (odds ratio [OR] 1.40 95% confidence interval: 0.95–2.04; P = 0.09. HIV RNA suppression was frequent (74% and mean CD4 count achieved robust (over 400 cells/μL at 6 months, irrespective of sex. The primary reasons for therapy interruption in females and males included: gastrointestinal intolerance (25% vs 19%; P = 0.42; poor adherence (22% vs 15%; P = 0.31; neuropsychiatric symptoms (19% vs 5%; P = 0.003; and lost to follow-up (3% vs 13%; P = 0.08. Seven males (5% and no females discontinued therapy for liver-specific complications. Death rate was higher in females (23% vs 7%; P = 0.003.Conclusion: There are subtle differences in the characteristics of female and male HIV–HCV coinfected patients that influence HIV treatment decisions. The reasons for treatment interruption and change differ by biological sex. This knowledge should be considered when starting HIV therapy and in efforts to improve treatment outcomes.Keywords: AIDS, HIV, HCV, coinfection, HAART, viral load, women, gender differences

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

    Directory of Open Access Journals (Sweden)

    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

  7. Acne vulgaris and acne rosacea as part of immune reconstitution disease in HIV-1 infected patients starting antiretroviral therapy.

    Science.gov (United States)

    Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David

    2008-07-01

    Immune reconstitution disease (IRD) has been widely reported following the commencement of antiretrovirals. We report a case series from a cohort of HIV-1-infected patients of whom four developed acne vulgaris and one developed acne rosacea after the initiation of antiretroviral therapy. Acne vulgaris, as part of IRD, has been reported only once in the literature, whereas acne rosacea has not, to our knowledge, previously been described. This serves as a reminder not to overlook dermatological manifestations of disease in patients with HIV infection after starting antiretrovirals.

  8. Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia-a new context for refeeding syndrome?

    Science.gov (United States)

    Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C

    2009-01-01

    High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries.

  9. Factors associated with esophageal candidiasis and its endoscopic severity in the era of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    So Nishimura

    Full Text Available Candidia esophagitis (CE is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART era.A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI endoscopy were analyzed. Sexual behavior, CD4(+ count, HIV-RNA viral load (VL, history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsi's grade I/II or severe (grade III/IV. Of the 733 subjects, 62 (8.46% were diagnosed with CE (mild, n = 33; severe, n = 29. Of them, 56.5% (35/62 had no GI symptoms, 30.6% (19/62 had CD4 + ≥200 cells/μL, and 55.3% (21/38 had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4(+ counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds. Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29 had no GI symptoms and 44.4% (8/18 had no oral candidiasis. Median CD4(+ counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04.Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis.

  10. Incidence of Severe Neutropenia in HIV-Infected People Starting Antiretroviral Therapy in West Africa

    Science.gov (United States)

    Leroi, Charline; Balestre, Eric; Messou, Eugene; Minga, Albert; Sawadogo, Adrien; Drabo, Joseph; Maiga, Moussa; Zannou, Marcel; Seydi, Moussa; Dabis, Francois; Jaquet, Antoine

    2017-01-01

    Background In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. Methods A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). Results Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6–9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8–2.6), ≥6–12 months (aHR = 2.1; 95% CI: 1.6–2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2–2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1–1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0–1.4). Conclusion The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation. PMID:28122041

  11. 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.

  12. Short Communication: Limited HIV Pretreatment Drug Resistance Among Adults Attending Free Antiretroviral Therapy Clinic of Pune, India.

    Science.gov (United States)

    Karade, Santosh; Patil, Ajit A; Ghate, Manisha; Kulkarni, Smita S; Kurle, Swarali N; Risbud, Arun R; Rewari, Bharat B; Gangakhedkar, Raman R

    2016-04-01

    In India, the roll out of the free antiretroviral therapy (ART) program completed a decade of its initiation in 2014. The success of first-line ART is influenced by prevalence of HIV pretreatment drug resistance (PDR) in the population. In this cross-sectional study, we sought to determine the prevalence of PDR among adults attending the state-sponsored free ART clinic in Pune in western India. Fifty-two individuals eligible for ART as per national guidelines with median CD4 cell count of 253 cells/mm(3) (inter quartile range: 149-326) were recruited between January 2014 and April 2015. Population-based sequencing of partial pol gene sequences from plasma specimen revealed predominant HIV-1 subtype C infection (96.15%) and presence of single-drug resistance mutations against non-nucleoside reverse transcriptase inhibitor in two sequences. The study supports the need for periodic surveillance, when offering PDR testing at individual level is not feasible.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...... count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating...

  14. Central nervous system penetration effectiveness of antiretroviral drugs and neuropsychological impairment in the Ontario HIV Treatment Network Cohort Study.

    Science.gov (United States)

    Carvalhal, Adriana; Gill, M John; Letendre, Scott L; Rachlis, Anita; Bekele, Tsegaye; Raboud, Janet; Burchell, Ann; Rourke, Sean B

    2016-06-01

    Since the introduction of combination antiretroviral therapy (cART), the incidence of severe HIV-associated neurocognitive impairment has declined significantly, whereas the prevalence of the milder forms has increased. Studies suggest that better distribution of cART drugs into the CNS may be important in reducing viral replication in the CNS and in reducing HIV-related brain injury. Correlates of neuropsychological (NP) performance were determined in 417 participants of the Ontario HIV Treatment Cohort Study (OCS). All participants were on three cART drugs for at least 90 days prior to assessment. Multiple logistic and linear regression methods were used. Most participants were Caucasian men with mean age of 47 years. About two thirds had a nadir CD4+ T-cell count below 200 cells/μL and 92 % had an undetectable plasma HIV viral load. The median CNS penetration effectiveness (CPE) score was 7. Sixty percent of participants had neuropsychological impairment. Higher CPE values significantly correlated with lower prevalence of impairment in bivariate and multivariate analyses. In this cross-sectional analysis of HIV+ adults who had a low prevalence of comorbidities and were taking three-drug cART regimens, greater estimated distribution of cART drugs into the CNS was associated with better NP performance.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Prevalence of Thrombocytopenia among Chinese Adult Antiretroviral-na(i)ve HIV-positive Patients

    Institute of Scientific and Technical Information of China (English)

    Hong-Wei Fan; Fu-Ping Guo; Yi-Jia Li; Ning Li; Tai-Sheng Li

    2015-01-01

    Background:The prevalence ofthrombocytopenia among Chinese antiretroviral therapy (ART)-na(i)ve HIV-infected adults has not been well-described.The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-na(i)ve HIV-infected adults.Methods:We performed a cross-sectional study of Chinese adult ART-na(i)ve HIV-infected patients from September 2005 through August 2014.Socio-demographic variables and laboratory results including platelets,CD4+ cell count,and viral load were obtained from medical records.Factors and outcomes associated with thrombocytopenia were assessed using logistic regression.Results:A total of 1730 adult ART-na(i)ve HIV-infected patients was included.The mean age was 38 years.The prevalence of thrombocytopenia was 4.5%.There were significant differences in the prevalence of thrombocytopenia between patients <30 years of age (2.8%) and 30-39 years (4.0%) compared with patients greater than 50 years (7.0%) (P =0.006 and P =0.044,respectively).The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm3 (3.3%) and >350 cells/mm3 (2.8%) compared with patients with CD4+ counts of50-199 cells/mm3 (7.1%) (P =0.002 and P =0.005,respectively).The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs.3.9% for HCV-Ab negative,P =0.001).We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection:Blood transmission (10.7%) versus men who have sex with men (3.9%) (P =0.002) and versus heterosexual transmission (3.9%) (P =0.001).In binary logistic regression analyses,age ≥>50 years,HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]:1.167,5.281,P=0

  17. Potential drug–drug interactions in HIV-perinatally infected adolescents on antiretroviral therapy in Buenos Aires, Argentina

    Directory of Open Access Journals (Sweden)

    Ezequiel Cordova

    2014-11-01

    Full Text Available Introduction: An increasing number of treatment-experienced perinatally HIV-infected adolescents (PHA are being transitioned from paediatric centres to adult HIV-care [1]. Most of them had been heavily exposed to antiretroviral drugs (ARVs, harbour drug-resistant viruses and require non-antiretroviral medication due to comorbidities [2]. This may predispose for clinically significant drug–drug interactions (CSDDIs [3]. There are no studies concerning CSDDIs in PHA. We aimed to evaluate the prevalence of concomitant medications and CSDDIs in PHA who were transitioned for adult HIV-care to the Infectious Diseases Unit, Cosme Argerich Hospital, Buenos Aires City, Argentina. Materials and Methods: Descriptive pilot cross-sectional study (March to June 2014. PHA under ARVs at the time of the study were assessed for concomitant medication. CSDDIs were screened and categorized using the University of Liverpool Drug Interactions Program (www.hiv-druginteractions.org [4]. Results: Forty-five patients were included. Female sex: 53%. Median (IQR age: 20 years (18–22. CDC-stage C was observed in 27 (79%; 50% had ≥1 comorbidities including 3 with HCV co-infection. Drug abuse was observed in 6 (13%. The median of prior ARV regimens was 3 (3–5. Current ARV regimen included: PI: 87%, NNRTI: 27%, INSTI: 20%, enfuvirtide: 7% and CCR5 inhibitor: 4%. Median CD4 T-cell count: 568 cells/mL (279–771. Viral load <50 copies/mL: 80%. Sixty percent (27/45 had ≥1 co-medications (median 1. The most frequent co-medications were NSAIDs (40%, hormonal therapy (19% and antimicrobials (19%. Use of herbal supplements was observed in 10 (22%. Overall, 23 (51% had ≥ 1 CSDDIs: 19/27 (70% with co-medication (orange flag=18 and red flag=1; and 2/10 (20% with herbal supplements. ARV–ARV interactions were observed in 4/45 (9%: unboosted atazanavir+tenofovir (n=2, unboosted atazanavir+efavirenz (n=1 and lopinavir/ritonavir+efavirenz (n=1 (all orange flag. Considering

  18. The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

    Science.gov (United States)

    Spada, Celso; Treitinger, Arício; Reis, Marcellus; Masokawa, Ivete Y; Verdi, Júlio C; Luiz, Magali C; Silveira, Mariete V S; Michelon, Cleonice M; Avila-Junior, Silvio; Gil, lone D O; Ostrowskyl, Stephanie

    2002-05-01

    Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

  19. The efficacy and safety of maraviroc addition to a stable antiretroviral regimen in subjects with suppressed plasma HIV-RNA is not influenced by age.

    Science.gov (United States)

    Blanco, José-Ramón; Arroyo-Manzano, David; Rojas-Liévano, John F; Crespo, Manuel; Bravo, Isa; Pasquau, Juan; Garcia Del Toro, Miguel; Herrero, Cristina; Rivero, Antonio; Moreno, Santiago; Llibre, Josep Maria

    2015-09-01

    There are few data about the immunovirological efficacy, safety/tolerability, and durability of maraviroc (MVC) addition to aging patients on suppressive antiretroviral therapy (cART) and undetectable viral load (HIV clinical trials. This study included 80 patients aged ≥50 years and 161 aged HIV history (≥15 years) (OR 0.43; p=0.016) or having <200/mm(3) CD4(+) T cells at MVC initiation (OR 0.27; p=0.004). Meanwhile, achieving a CD4/CD8 ratio ≥0.5 at week 48 was less likely in those with CD4(+) T cell counts <200 at MVC initiation (OR 0.09; p<0.0001) or with a previous AIDS event (OR 0.43; p=0.028). In summary, the immunovirological efficacy, safety/tolerability, and durability of MVC addition in patients virologically suppressed were independent of the patient's age at treatment onset.

  20. Impact of injecting drug use on response to highly active antiretroviral treatment in HIV-1-infected patients: a nationwide population-based cohort study

    DEFF Research Database (Denmark)

    Larsen, Mette Vang; Omland, Lars; Gerstoft, Jan;

    2010-01-01

    The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted...... for non-IDUs, and IDUs initiated HAART later than non-IDUs. In conclusion, more than half of the HIV-infected patients in Denmark infected through injecting drug use gained full viral suppression after initiating HAART. Absolute CD4(+) cell count was lower and mortality higher among IDUs than non-IDUs....... a nationwide population-based cohort study of all HIV-infected patients who initiated HAART during the study period of 1 January 1995 to 31 December 2007. We compared changes in CD4(+) cell counts, percentage of full viral suppression (