AIDS research and human retroviruses
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AIDS Res. Hum. Retroviruses · Feb 2017
Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4+ T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses.
HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4+ T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4+ T cell deficiency on ART. Aviremic HIV patients with nadir CD4+ T cell counts <100 cells/μL and who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (<350 cells/μL; n = 13) or normal (>500 cells/μL; n = 20) CD4+ T cell counts. ⋯ After anti-CD3 stimulation, induction of CD27hiCD28hi expression was independent of CD4+ T cell counts, but lower in HIV patients than in healthy controls. Induction of CD27hiCD28hi expression correlated with induction of Ki67 expression in total, naïve, and CD31+ naïve CD4+ T cells from patients. In HIV patients responding to ART, impaired induction of CD27 and CD28 on CD4+ T cells after stimulation with anti-CD3 is associated with poor proliferative responses as well as greater CD4+ T cell activation and immunosenescence.
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AIDS Res. Hum. Retroviruses · Jan 2017
Review Meta AnalysisAssociation Between the Interleukin-10-1082G/A, -592C/A, -819C/T Gene Polymorphism and HIV-1 Susceptibility: A Meta-Analysis.
The Interleukin-10 (IL-10) gene polymorphism influences the pathogenesis and evolution of HIV-1 disease. Many studies in this regard have evaluated the association between this polymorphism and HIV-1 susceptibility, yet, the exact relationship between them remains ambiguous and contradictory. A systematic literature search was conducted and the found case-control studies assessing the association between IL-10-1082G/A, -592C/A, -819C/T gene polymorphism and HIV-1 susceptibility were analyzed. ⋯ AA model: OR = 1.32, 95% CI = 0.95-1.84, p = .094; GG+AA vs. AG model: OR = 0.92, 95% CI = 0.72-1.19, p = .537). In general, the meta-analysis found no marked association between the IL-10-1082G/A gene polymorphism and HIV-1 susceptibility, IL-10-529C/A gene polymorphism might lead to a decreased risk of HIV-1 infection, and IL-10-819C/T gene polymorphism might lead to an increased risk of HIV-1 infection.
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AIDS Res. Hum. Retroviruses · Apr 2016
The Association of Gender, Age, Efavirenz Use, and Hypovitaminosis D Among HIV-Infected Adults Living in the Tropics.
Vitamin D, which is important for calcium homeostasis and bone metabolism, has several noncalcemic actions. Low vitamin D levels have been observed in HIV-infected patients from high latitudes, with consequently reduced bone mineral density (BMD), but data from the tropics are scarce. We aimed to determine the prevalence of and risk factors for hypovitaminosis D among HIV-infected patients in the tropics. ⋯ In multivariate analysis, female gender [odds ratio: OR (95% confidence interval: 95% CI) 1.7 (1.2-2.3), p = 0.005], age >37 years [OR (95% CI) 1.6 (1.1-2.4), p = 0.01], and EFV use [OR (95% CI) 2.0 (1.3-3.2), p = 0.004] were independent predictors of hypovitaminosis D. Even in tropical areas where the sun is abundant, hypovitaminosis D is highly prevalent. Thus, treatment of low vitamin D in HIV-infected patients at high risk should not be ignored to prevent reductions in BMD and other hypovitaminosis D-related comorbidities.
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AIDS Res. Hum. Retroviruses · Jan 2016
Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada.
The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4(+) count. ⋯ After 3 years of ART, 22% of individuals with a normal BMI (18.5-24.9 kg/m(2)) at baseline had become overweight (BMI 25.0-29.9 kg/m(2)), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future.
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AIDS Res. Hum. Retroviruses · Nov 2015
Randomized Controlled TrialA Phase 1 Randomized, Blinded Comparison of the Pharmacokinetics and Colonic Distribution of Three Candidate Rectal Microbicide Formulations of Tenofovir 1% Gel with Simulated Unprotected Sex (CHARM-02).
CHARM-02 is a crossover, double-blind, randomized trial to compare the safety and pharmacokinetics of three rectally applied tenofovir 1% gel candidate rectal microbicides of varying osmolalities: vaginal formulation (VF) (3111 mOsmol/kg), the reduced glycerin vaginal formulation (RGVF) (836 mOsmol/kg), and an isoosmolal rectal-specific formulation (RF) (479 mOsmol/kg). Participants (n = 9) received a single, 4 ml, radiolabeled dose of each gel twice, once with and once without simulated unprotected receptive anal intercourse (RAI). The safety, plasma tenofovir pharmacokinetics, colonic small molecule permeability, and SPECT/CT imaging of lower gastrointestinal distribution of drug and virus surrogate were assessed. ⋯ VF had the most adverse events, highest plasma tenofovir concentrations, greater mucosal permeability of the drug surrogate, and most proximal colonic luminal migration compared to RF and RGVF formulations. There were no major differences between RF and RGVF formulations. Simultaneous assessment of toxicity, systemic and luminal pharmacokinetics, and colocalization of drug and viral surrogates substantially informs rectal microbicide product development.