Immune activation persists despite suppressive antiretroviral therapy (ART) and may be affected by sex or body composition. We hypothesized that weight gain, sex and BMI would be associated with changes in immune activation following ART initiation and explored these relationships in a selected subset of women and men initiating ART in two large randomized ACTG trials (A5202 and A5257).
A purposeful sampling design selected participants who achieved virologic suppression on ART and either maintained weight within +/- 0.5 kg/m2 (‘maintainers’) or gained 2.6-6.4 kg/m2 (‘gainers’) from baseline to 96 weeks. We measured IL-6, sTNF-RI and II, IP-10, hsCRP, sCD14 and sCD163 at weeks 0 and 96. Multivariable linear regression explored associations of weight gain (gainers vs maintainers), sex, and pre-ART BMI with outcomes of pre-ART biomarker concentrations and changes from baseline to week 96, adjusting for baseline age, race/ethnicity, ART regimen, CD4 count and HIV-1 RNA.
340 participants were selected; median pre-ART age 42 years, CD4+ cell count 273 cells/mm3, HIV-1 RNA 4.7 log10 copies/mL; 49% were women, 33% white, 42% black, and 24% Hispanic. Pre-ART biomarker concentrations were similar in women and men (data not shown). While pre-ART BMI was similar between gainers and maintainers (overall and within sex), gainers had significantly lower pre-ART CD4 vs maintainers. In adjusted models among those with normal pre-ART BMI, pre-ART IL-6, sTNF-RII, IP-10, and sCD163 were higher for gainers versus maintainers. Association of weight gain on week 96 changes of these 4 biomarkers differed by sex; women who gained weight had smaller declines in biomarkers compared to men who gained (see Table). For IL-6, for women, gaining weight was associated with attenuating changes by 0.05 (difference between model-based means), whereas for men, gaining weight was associated with increasing changes by 0.13. For sTNF-RII, the association between weight gain and changes in sTNF-RII also varied by pre-ART BMI.
Higher pre-treatment immune activation markers are significantly associated with weight gain following ART initiation even after controlling for pre-ART CD4 counts. Weight gain attenuates the decline in several immune activation markers following ART initiation among women; thus, women may be at increased risk for complications of weight gain. Identifying individuals at risk of weight gain may allow for targeted investigation of preventive interventions.