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SEX AND OBESITY ARE ASSOCIATED WITH RESIDUAL VIREMIA IN ART-SUPPRESSED INDIVIDUALS
Joshua C. Cyktor1, Hanna Mar2, Ann Collier3, Evelyn Hogg4, Catherine Godfrey5, Joseph J. Eron6, Ronald Bosch2, Deborah McMahon1, John W. Mellors1, Rajesh T. Gandhi7
1University of Pittsburgh, Pittsburgh, PA, USA,2Harvard University, Boston, MA, USA,3University of Washington, Seattle, WA, USA,4Social & Scientific Systems, Silver Spring, MD, USA,5DAIDS, NIAID, Bethesda, MD, USA,6University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,7Massachusetts General Hospital, Boston, MA, USA
The sex of an individual influences HIV levels prior to antiretroviral therapy (ART) and adipose tissue has been proposed to harbor part of the HIV reservoir. The effect of host characteristics, including sex and body-mass index (BMI), on HIV persistence during ART remains incompletely understood. We evaluated factors associated with HIV persistence in a cohort of people with long-term virologic suppression (ACTG A5321).
Participants who initiated ART during chronic infection with sustained virologic suppression had measurements of plasma HIV RNA by single copy assay (SCA), cell-associated HIV DNA and RNA (CA-DNA, CA-RNA). We assessed the effect of age, sex (reported at birth), BMI, waist circumference (WC), years on ART, pre-ART HIV RNA, pre-ART CD4 count, initial ART regimen (PI, NNRTI or INSTI) on HIV persistence. Assessments were done at study entry or, for WC, at pre-study visit.
295 participants (53 females) were evaluated; median (IQR) age 48yr (41, 54); yrs on ART 7 (6, 10); BMI 27 (24, 31); WC 94cm (87, 102). CA-DNA, CA-RNA and plasma SCA were positively correlated with pre-ART HIV RNA (r=0.35, 0.29, 0.20; respectively, p-values <0.001), and negatively with pre-ART CD4 count (-0.35, -0.21, -0.12, respectively, all p <0.05). Regimen type was not associated with HIV persistence markers after controlling for ART duration. Males were more likely than females to have plasma SCA values ≥0.4 copies/mL (52% vs 29%, p=0.003) (Figure), even after adjusting for age, pre-ART HIV RNA and CD4 count, years on ART and BMI (p=0.004). Higher BMI and higher WC were each associated with higher SCA levels (r=0.12 and 0.13, p<0.04) after adjustment for age, sex, pre-ART HIV RNA and CD4 count, and years on ART. The proportion of participants with detectable residual viremia increased in a step-wise fashion by BMI category: normal/underweight 38%; overweight 50%; obese 55% (Figure). Sex, BMI and WC were not associated with CA-DNA or CA-RNA.
Higher BMI and obesity are associated with higher levels of residual viremia in persons on long-term ART. Adipose tissue may be an important site of HIV production due to its proinflammatory milieu or altered ARV penetration. The finding that females have lower residual viremia than males may reflect effects of estrogen on HIV expression or other biologic and immunologic differences. Studies of the mechanism by which obesity and sex affect HIV persistence are needed to inform cure strategies.