Cumulative Low-Level Viremia Is Not Associated With Endothelial Function in Black African Adults With HIV

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Abstract
Background: People with HIV (PWH) experience excess cardiovascular disease risk with persistent inflammation considered a key driver, despite antiretroviral therapy. Low-level viremia (LLV) may contribute to inflammation and vascular injury, but data in sub-Saharan Africa are limited. We assessed correlates of endothelial function among Black African PWH with a history of viremia despite antiretroviral therapy use. Methods: We conducted a cross-sectional substudy within the South African UTRA trial (NCT05333679). Endothelial function was measured with EndoPAT using the natural log-transformed Reactive Hyperemia Index (LnRHI); endothelial dysfunction was defined as LnRHI ≤ 0.51. The primary exposure was 12-month cumulative HIV viral load (VL) area under the curve. Body mass index, waist-to-hip ratio, and Body Roundness Index were modeled using adjusted natural cubic splines with robust standard errors. We evaluated associations of various covariates, including these body composition metrics, with LnRHI via multivariable regression. Results: Of 120 participants (median age 46 years, 69% women), 26% met criteria for endothelial dysfunction despite low 10-year cardiovascular disease risk. Median LnRHI was 0.69 (interquartile range 0.50–0.94). Mean cumulative VL area under the curve was 1.55 log 10 copy-yr/mL (interquartile range 1.30–2.20), consistent with LLV. Cumulative VL was not associated with endothelial function after adjustment. By contrast, LnRHI varied significantly and nonlinearly across body mass index, waist-to-hip ratio, and Body Roundness Index, with an overall downward trend with increasing adiposity. Conclusions: In this cross-sectional analysis of Black African PWH with LLV, no association between cumulative VL and endothelial dysfunction was observed. However, higher adiposity was consistently associated with declining endothelial function. Our data add to the growing evidence on the importance of addressing body composition as a multifactorial risk determinant and important correlate of early vascular risk in PWH.
Funding Information
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (R01AI152119)
  • Fogarty International Center (D43TW010937)
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (R01AI143340)
  • Division of Research Capacity Development
  • Discovery Foundation

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