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Sex-associated differences in pre-antiretroviral therapy plasma HIV-1 RNA in diverse areas of the world vary by CD4(+) T-cell count.

ABSTRACT: BACKGROUND:Sex differences in the natural history of HIV infection may vary between resource-rich and resource-limited settings. METHODS:Baseline characteristics from a randomized clinical trial of treatment-naive subjects conducted at sites in Africa, Asia, the Caribbean, and North and South America were analysed to determine if there were significant differences by sex. RESULTS:Of the 1,571 participants, 740 (47.1%) were women. Women had higher mean screening CD4(+) T-cell counts (mean 15 cells higher; P<0.001), lower mean haemoglobin and creatinine clearance, a lower mean baseline HIV-1 viral load (4.85 log(10) versus 5.05 log?? copies/ml; P<0.001) and were less likely to have a prior AIDS diagnosis than men. The sex difference in viral load was related to CD4(+) T-cell count; however, it was independent of country and persisted within the strata with CD4(+) T-cell count <200 cells/mm³. CONCLUSIONS:Women in resource-limited settings have lower levels of plasma HIV-1 RNA and appear to present for enrolment into clinical trials at an earlier stage of disease than men. The biological basis for lower viral load in women compared to men remains unexplained. It will be important to determine if the sex differences observed at baseline impact clinical outcomes once the PEARLS clinical trial is completed.

SUBMITTER: Grinsztejn B

PROVIDER: S-EPMC3205462 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Sex-associated differences in pre-antiretroviral therapy plasma HIV-1 RNA in diverse areas of the world vary by CD4(+) T-cell count.

Grinsztejn Beatriz B Smeaton Laura L Barnett Ronald R Klingman Karin K Hakim James J Flanigan Timothy T Kumarasamy N N Campbell Thomas T Currier Judith J

Antiviral therapy 20110101 7

<h4>Background</h4>Sex differences in the natural history of HIV infection may vary between resource-rich and resource-limited settings.<h4>Methods</h4>Baseline characteristics from a randomized clinical trial of treatment-naive subjects conducted at sites in Africa, Asia, the Caribbean, and North and South America were analysed to determine if there were significant differences by sex.<h4>Results</h4>Of the 1,571 participants, 740 (47.1%) were women. Women had higher mean screening CD4(+) T-cel ...[more]

PMID: 22024521

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Project description:High levels of adherence to antiretroviral therapy (ART) are necessary for achieving and maintaining optimal virological suppression, as suboptimal adherence leads to therapy failure and disease progression. It is well known that adherence to ART predicts therapy response, but it is unclear whether clinical outcomes of ART predict adherence. To examine the predictive power of current CD4+ T cell count for adherence of HIV-infected individuals to ART, we performed a cross-sectional analysis of 133 Dutch HIV patients with electronically measured adherence. In a multivariate analysis adjusting for a number of sociodemographic and clinical variables, high current CD4+ T cell count (>660 cells/mm3) was most strongly associated with lower adherence to ART (assessed as a continuous variable) during a two-month period immediately following the measurements of variables (P = 0.008). The twice-per-day (versus once-per-day) dosing regimen was also significantly associated with lower adherence (P = 0.014). In a second multivariate analysis aimed at determining the predictors of suboptimal (<100% of the doses taken) adherence, high current CD4+ T cell count was again the strongest independent predictor of suboptimal adherence to ART (P = 0.015), and the twice-per-day dosing regimen remained associated with suboptimal adherence (P = 0.025). The association between suboptimal adherence and virological suppression was significant in patients with high CD4+ T cell counts, but not in patients with low or intermediate CD4+ T cell counts (P = 0.036 and P = 0.52, respectively; P = 0.047 for comparison of the effects of adherence on virological suppression between patients with high vs. low or intermediate CD4+ T cell counts), suggesting that apart from promoting suboptimal adherence, high CD4+ T cell count also strengthens the effect of adherence on virological suppression. Therefore, sustained efforts to emphasize continued adherence are necessary, especially for patients with high CD4+ T cell counts.

Project description:BackgroundThere is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.Methodology/principal findingsTo estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (? = 42.8; 95% CI, -2.1 to 87.7) or after the first year of ART (? = ?-9.9; 95% CI, -24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (? = 63.0; 95% CI, 6.0 to 120.1) in females.Conclusions/significanceEmpiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

Dataset Information

Sex-associated differences in pre-antiretroviral therapy plasma HIV-1 RNA in diverse areas of the world vary by CD4(+) T-cell count.

Publications

Sex-associated differences in pre-antiretroviral therapy plasma HIV-1 RNA in diverse areas of the world vary by CD4(+) T-cell count.

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