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

Abstract

BACKGROUND: People with HIV (PWH) experience excess cardiovascular disease (CVD) risk with persistent inflammation considered a key driver, despite antiretroviral therapy (ART). Low-level viraemia (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 viraemia despite ART use. METHODS: We conducted a cross-sectional sub-study within the South African UTRA trial (NCT05333679). Endothelial function was measured with EndoPAT using the natural log-transformed reactive hyperaemia 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 (AUC). Body-mass index (BMI), waist-to-hip ratio (WHR), and body roundness index (BRI) were modelled 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 CVD risk. Median LnRHI was 0.69 (IQR 0.50-0.94). Mean cumulative VL AUC was 1.55 log10 copy-years/mL (IQR 1.30-2.20), consistent with LLV. Cumulative VL was not associated with endothelial function after adjustment. In contrast, LnRHI varied significantly and non-linearly across BMI, WHR, and BRI, 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 adds 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.