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

Abstract

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.

Keywords: HIV; immune activation; inflammation; sex differences; weight gain.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Estimated biomarker levels before ART initiation. Estimates from final multivariable model with the following inputs across subgroups: age 40–49 years, white race, non-Hispanic ethnicity, pre-ART CD4 cell count of 272 cells/mm3, pre-ART plasma HIV-1 RNA of 4.65 log10 copies/mL, assigned ART regimen atazanavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate, and in models not showing subgroups by sex, male. Abbreviations: ART, antiretroviral therapy; BMI, body mass index; CXCL-10, C-X-C motif chemokine 10; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; sCD163, soluble CD163.

Figure 2.

A, Estimated differences between weight gainers and maintainers by sex in biomarker level changes from pre-ART to week 96. Estimates from final multivariable model including the following covariates: race/ethnicity, age (decade), pre-ART CD4 count and plasma HIV-1 RNA, and pre-ART BMI group. B, Estimated differences between pre-ART BMI category (vs normal BMI) in biomarker level changes from pre-ART to week 96. Estimates from final multivariable model including the following covariates: sex, race/ethnicity, age (decade), pre-ART CD4 count, and plasma HIV-1 RNA. Differences were significantly larger than normal BMI for IL-6 and hsCRP. Untransformed units for biomarkers were pg/mL for IL-6, sTNF-RI, and CXCL-10; μg/mL for hsCRP; and ng/mL for sCD163. Abbreviations: ART, antiretroviral therapy; BMI, body mass index; CXCL-10, C-X-C motif chemokine 10; HIV, human immunodeficiency virus; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; sCD163, soluble CD163; sTNF-RI, soluble TNF-α receptor I.