Male sex and high body mass index (BMI) were found to be independently associated with residual viremia in people with HIV-1 on long-term suppressive antiretroviral therapy (ART), according to study results published in the Journal of Infectious Diseases.

This cross-sectional study included 295 adults who had initiated ART for chronic HIV-1 infection and had sustained virologic suppression (duration of ART was ≥4 years) to determine whether sex, adiposity, and/or ART regimen were associated with markers of HIV-1 persistence including residual viremia. Participants had plasma HIV-1 RNA levels <50 copies/mL as determined by commercial assays at or before week 48 of ART and at all subsequent time points, with no reported ART interruptions >21 days. Measurements of HIV-1 persistence, inflammation, and T-cell activation were performed on blood samples obtained during ART and with plasma HIV-1 RNA <40 copies/mL.

Of the 295 participants, 18% were women and the median age was 48 years. Median weight, hip circumference, and waist circumference were 81.6 kg, 99.5 cm, and 94.4 cm, respectively. Median BMI was 27.0 kg/m2;31% were normal/underweight, 42% were overweight, and 27% were obese.

Men were found to be substantially more likely than women to have detectable plasma HIV-1 RNA ≥0.4 copies/mL (52% vs 29%; P =.003). This relationship between sex and residual viremia persisted after adjusting for participant age, pre-ART plasma HIV-1 RNA and CD4+ T-cell counts, years on ART, and BMI (P =.004). Furthermore, the association remained when further adjusting for race and ethnicity.


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Higher BMI and larger waist circumference were each associated with more frequent detection of residual viremia (r=0.12 and 0.13, respectively; P <.04). These associations persisted after adjustment for age, sex, pre-ART HIV-1 RNA and CD4+ cell counts, and years on ART. Again, the associations remained when correlations were further adjusted for race and ethnicity. Although the correlation between BMI and residual viremia was modest, the proportion of participants with detectable viremia increased in a stepwise fashion by BMI category: normal/underweight, 38%; overweight, 50%; obese, 55%.

Of the soluble inflammatory markers measured (interleukin [IL]-6, P-10, neopterin, sCD163, sCD14, and tumor necrosis factor), women had higher peripheral levels of IL-6, sCD14, and sCD163 than men, but there was no significant association between T-cell activation or proliferation with sex or BMI; only IL-6 was positively associated with BMI (r=0.3; P <.001). None of the soluble inflammatory markers assayed were associated with any of the measures of HIV-1 persistence.

After controlling for ART duration, ART regimen type was not associated with measures of HIV-1 persistence.

“Further study is needed to determine whether the origin of residual viremia is adipose tissue or if there are indirect effects of fat on virus production and/or clearance at other sites,” concluded the researchers. “Additional studies to confirm these relationships and to define the mechanisms by which sex and obesity affect HIV-1 persistence are needed to inform HIV-1 cure strategies,” they added.

Disclosure: John W. Mellors, MD, and Rajesh T. Gandhi, MD, declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of their disclosures.

Reference

Cyktor JC, Bosch RJ, Mar H, et al; ACTG A5321 Team. Male sex and obesity are associated with residual plasma HIV-1 viremia in persons on long-term antiretroviral therapy [published online June 30, 2020]. J Infect Dis. doi:10.1093/infdis/jiaa373