The Association Between Weight Gain, Sex, and Immune Activation Following the Initiation of Antiretroviral Therapy

Background. Immune activation persists despite suppressive antiretroviral therapy (ART) and may be affected by sex or body composition. We explored these relationships in a subset of participants who initiated ART in two large randomized trials. Methods. Purposeful sampling selected participants who achieved virologic suppression on ART and either maintained weight within ± 0.5 kg/m² or gained 2.6–6.4 kg/m² from baseline to 96 weeks. We measured 7 markers of inflammation and immune activation at weeks 0 and 96. Multivariable linear regression explored associations of weight gain, sex, and pre-ART BMI with pre-ART and changes in biomarker concentrations. Results. 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. Among participants with a normal pre-ART BMI, higher pre-ART levels of IL-6, sTNF-RI and RII, CXCL-10, sCD163 and hsCRP were associated with weight gain. Association of weight gain with week 96 changes of these biomarkers differed by sex; women who gained weight had smaller declines in most measured biomarkers compared to men who gained. Conclusions. Among women, weight gain is associated with attenuated decline in several immune activation markers following ART initiation.