To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Risk ratios (relative risks, odd ratios, and hazard ratios) and 95% confidence intervals were obtained. Sixty-five articles were included in this review. Thirty-nine studies were from North America and Europe and 26 were from Latin America, Asia, and Africa. Forty-four studies (68%) showed no statistically significant difference in risk of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Decreased risk of death among females compared to males was observed in 24 of the 25 articles that included mortality analyses [pooled risk ratio 0.72 (95% confidence interval=0.69-0.75)], and decreased risk of death or AIDS was observed in 9 of the 13 articles that examined the composite outcome [pooled risk ratio=0.91 (0.84-0.98)]. There was no significant effect of sex on the risk of progression to AIDS [pooled risk ratio=1.15 (0.99-1.31)]. In this systematic review, females starting HAART appeared to have improved survival compared to males. However, this benefit was not associated with decreased progression to either AIDS or to differences in virologic or immunologic treatment outcomes.

This retrospective cohort study of HIV-infected women receiving highly active antiretroviral therapy (HAART) while pregnant assessed the effect of postpartum HAART discontinuation on maternal AIDS-defining events (ADEs), non-AIDS-defining events (non-ADEs), and death 1997-2008 in Nashville, Tennessee. Cox proportional hazards models compared rates of ADE or all-cause death and non-ADE or all-cause death, and competing risks analyses compared rates of ADE or ADE-related death and non-ADE or non-ADE-related death across the groups. There were two groups: women who stopped HAART postpartum (discontinuation, n ¼ 54) and women who continued HAART postpartum (continuation, n ¼ 69). Fifty percent were African American, 40% had prior non-HAART antiretroviral therapy (ART) use, and 38% had a history of illicit drug use. Median age was 27.5 years, baseline CD4(%) was 532 (34%) and CD4 nadir was 332 cells=mm 3 , baseline and peak HIV-1 RNA were 2.6 and 4.32 log 10 copies per milliliter, respectively. Women in the continuation group were older, had lower baseline CD4, CD4%, and CD4 nadir, and had higher peak HIV-1 RNA. In multivariable proportional hazards models, the hazard ratios [95% confidence interval (CI)] of ADE or all-cause death and non-ADE or all-cause death were lower in the continuation group, but not statistically significantly: 0.50 (0.12, 2.12; p ¼ 0.35) and 0.69 (0.24, 1.95; p ¼ 0.48), respectively. The results were similar in competing risks analyses. Despite having characteristics associated with worse prognosis, women who continued HAART postpartum had lower hazard ratio point estimates for ADEs or death and non-ADEs or death than women who discontinued HAART. Larger studies with longer follow-up are indicated to assess this association.

BackgroundPregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.MethodsWe conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).ResultsWomen initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (−0.35 vs. 0.10 log10 copies/mL, P = 0.03 and 183.8 vs. −70.8 cells/mm3, P = 0.03, respectively) but similar to those initiating HAART before pregnancy (−0.32 log10 copies/mL, P = 0.96 and 155.8 cells/mm3, P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups.ConclusionsHAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

BackgroundSome retrospective studies have found that HIV-infected women have a higher mortality risk than men after adjusting for baseline characteristics, while others have not. Anemia is a known predictor of HIV-related mortality. We assessed whether anemia contributed to the sex difference in mortality in our cohort.MethodsWe conducted a retrospective cohort study among HIV-infected persons in care at the Comprehensive Care Center (Nashville, TN) between 1998 and 2009. Cox proportional hazards models compared time from first clinic visit to death and AIDS-defining events (ADE), adjusted for baseline characteristics with and without baseline hemoglobin.ResultsOf 3,633 persons, 879 (24%) were women. Women had lower median baseline hemoglobin compared to men: 12.4 g/dL (inter-quartile range (IQR) 11.3–13.4) vs. 14.4 (IQR 13.1–15.5), respectively (P<0.001). In multivariable models without hemoglobin, the risk of death was higher among women: hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.17, 1.82; P = 0.001). In multivariable models with hemoglobin, the risk of death in women was diminished and no longer statistically significant: HR 1.2 (95% CI 0.93, 1.55; P = 0.17). The risk of ADE was higher among women in both models, but not statistically significant: HR 1.1 (95% CI 0.85–1.42; P = 0.46) in the model without hemoglobin and 1.11 (95% CI 0.82–1.48; P = 0.50) in the model with hemoglobin. Hemoglobin was a strong predictor of death: HR 0.88 per 1 g/dL increase (95% CI 0.83, 0.93; P<0.001).ConclusionIn our study population of HIV-infected persons in care, women had lower baseline hemoglobin, and lower hemoglobin contributed to their higher risk of ADE and death.