Obesity is prevalent among HIV-infected individuals on antiretroviral therapy (ART). Cross-sectional studies have suggested that HIV-infected women are more likely to be overweight or obese than men. Observational studies evaluating sex differences in body mass index (BMI) increases following ART initiation are conflicting. Three ACTG U.S.-based randomized trials (A5142, A5202 and A5257) assessed changes in BMI over 96 weeks during 2005-2013 in treatment-naïve individuals initiating ART. We performed a pooled analysis of these studies to estimate whether BMI changes in the first 96 weeks following initiation of ART differed by sex at birth.
BMI data over 96 weeks following ART initiation were compared between 760 women and 3041 men in the three contributing clinical trials. Analysis excluded participants not starting ART and women who became pregnant. Multivariable linear regression estimated the relationship between sex and change in BMI from baseline to week 96.
Women were older than men (mean 40.5 vs 37.7 years), and more likely to be black, non-Hispanic (58% vs 31%). Baseline CD4 count did not differ (mean 261 cells/mm3). Mean baseline BMI was higher in women vs men (28.4 vs 25.2 kg/m2), and fewer women were categorized as normal weight (32% vs 51%). After 96 weeks, women gained an average of 1.91 kg/m2 (95% CI 1.64, 2.19), men 1.39 kg/m2 (95% CI 1.30, 1.48); p for sex difference <.001; the sex difference persisted within each baseline BMI subgroup (see Table). After adjusting for baseline age, BMI, CD4 count, HIV-1 RNA, race/ethnicity, study and ART, mean BMI change for women was on average 0.63 kg/m2 (95% CI 0.41, 0.85) more than for men (p<.001). More women moved from normal to overweight/obese BMI category (40% of normal-weight women vs. 33% of normal-weight men). Statistical interactions were observed between sex and both baseline CD4 count and baseline HIV-1 RNA and suggest that for subgroups with higher viral load and lower CD4 at baseline, the estimated BMI changes in women are even larger than the average estimated difference.
In this pooled analysis, HIV-1 infected women experienced a significantly greater increase in BMI following ART initiation than men. These sex differences, even for women in the obese BMI category at baseline, suggest a problem of real clinical significance to women living with HIV. Future work will explore the impact of immune activation on these observations.