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. Clinical Trials Registration. NCT00811954 and NCT00811954.