Gender Differences in Immune Reconstitution: A Multicentric Cohort Analysis in Sub-Saharan Africa

University of Cape Town, South Africa
PLoS ONE (Impact Factor: 3.23). 02/2012; 7(2):e31078. DOI: 10.1371/journal.pone.0031078
Source: PubMed


In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution.
Antiretroviral-naïve adults who received ART for at least 9 months in four HIV programs in sub-Saharan Africa were included. Multivariate mixed linear models were used to examine gender differences in immune reconstitution on first line ART. A total of 21,708 patients (68% women) contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART were 149 [IQR 85-206] for women and 125 cells/µL [IQR 63-187] for men. After the first year on ART, immune recovery was higher in women than in men, and gender-based differences increased by 20 CD4 cells/µL per year on average (95% CI 16-23; P<0.001). Up to 6 years after ART start, patients with low initial CD4 levels experienced similar gains compared to patients with high initial levels, including those with CD4>250 cells/µL (difference between patients with <50 cells/µL and those with >250 was 284 cells/µL; 95% CI 272-296; LR test for interaction with time p = 0.63). Among patients with initial CD4 count of 150-200 cells/µL, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4-2.5) and men after 4.5 years (95% CI 4.1-4.8) of ART use.
Women achieved better long-term immune response to ART, reaching CD4 level associated with lower risks of AIDS related morbidity and mortality quicker than men.

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    • "The number of men was significantly greater than that of women for studies in Table 3 and could have affected study outcomes. Some studies, not included in our review because data on menopause were not reported, suggest that immunological and/or virological responses to ART differ by gender and among all age groups after adjusting for other factors [22, 65, 66]. "
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    ABSTRACT: More than half of persons living with HIV infection in the United States (U.S.) will be ≥50 years of age by 2020, including postmenopausal women. We conducted a systematic literature review about the effects of (1) HIV infection on age at menopause and (2) menopause on antiretroviral therapy (ART) response, in order to inform optimal treatment strategies for menopausal women living with HIV infection. We used the Ovid Medline database from 1980 to 2012. We included studies that focused on HIV-infected persons, included postmenopausal women, and reported outcome data for either age at menopause or response to ART across menopause. We identified six original research articles for age at menopause and five for response to ART across menopause. Our review revealed that current data were conflicting and inconclusive; more rigorous studies are needed. Disentangling the effects of menopause requires well-designed studies with adequate numbers of HIV-infected and HIV-uninfected women, especially disproportionately affected women of color. Future studies should follow women from premenopause through menopause, use both surveys and laboratory measurements for menopause diagnoses, and control for confounders related to normal aging processes, in order to inform optimal clinical management for menopausal women living with HIV.
    Full-text · Article · Dec 2013 · Obstetrics and Gynecology International
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    • "Contrary to other studies [4,9,23,37,38,39], in our analysis older age at initiation was not associated with lower immune recovery which has been attributed to decreasing thymic reserves [40,41]. Notwithstanding the differences in the definition of viral suppression, our findings were consistent with another study in Senegal with median age 37 years that did not demonstrate an effect of age on immune reconstitution [27]. "
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    ABSTRACT: There is conflicting data on long-term CD4 immune recovery after combination antiretroviral therapy (ART) in resource-limited settings. Virologic suppression is rarely documented in cohorts from sub-Saharan Africa so objective evidence of adherence is biologically unsubstantiated. We sought to investigate long-term patterns of immune recovery in Ugandan patients on ART with sustained viral suppression. A prospective cohort of patients starting ART between April, 2004 and April, 2005 at the Infectious Diseases Institute with sustained viral suppression (viral load ≤400 copies/ml at month 6 and 12) while on first-line ART. Propensity scores were used to adjust for treatment allocation (nevirapine or efavirenz) at ART initiation. Data were analyzed using Kaplan Meier methods and cross-sectional time series regression. Three hundred and fifty-six patients were included in the analysis.71.6% were female, 87% in WHO stage 3 or 4, median age was 37 years, (IQR:32-43), and median CD4 count was 108 cells/µL, (IQR:35-174) at ART start. At multivariable analysis, lower immune recovery (measured by change in CD4 from ART start at each time interval) was associated with male-gender (-59, 95% CI: 90, -28, P<0.001), baseline CD4 count of 101-200 cells/µL (-35, 95% CI: 62, -9, P=0.009) and >200 (-64, 95% CI: 101, -26, P=0.001), and use of AZT at baseline (-47, 95% CI: -74, -20, P=0.001). Median time to reach >400 cells/µL was longer in males (197.4 weeks, IQR:119.9-312.0), compared to females (144.7 weeks, IQR:96.6-219.7, P<0.001). The cumulative probability of attaining CD4 >400 cells/µL over 7 years was higher in females compared to males (P<0.001). There was long-term, continuous, immunologic recovery up to 7 years after ART initiation in an urban Ugandan cohort. Virologically suppressed women had better sustained immune recovery than men. Men take longer to immune reconstitute and have a lower probability of reaching a CD4 cell count >400 cells/µL. The biologic mechanisms of these gender differences need further exploration.
    Full-text · Article · Aug 2013 · PLoS ONE
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    • "The progression rates to AIDS and clinical manifestations of diseases associated with HIV infection might differ between women and men because of biological and socioeconomic factors [8]. Previous investigations found different rates of HIV disease progression and of virological and immunological response to antiretroviral therapy among HIV-infected women compared with men [9,10]. Some evidence suggests that HIV positive men have worse treatment outcomes than their women counterparts in Africa [11]. "
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    ABSTRACT: Background We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors. Methods We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. Results Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02). Conclusion We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences.
    Full-text · Article · Jan 2013 · BMC Public Health
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