Camilla Pennefather

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.

Stroke among people with HIV (PWH) has been linked to initiating or reinitiating antiretroviral therapy (ART) within six months.1,2,3 We examined this association in a large prospective cohort. We conducted a descriptive interim analysis of data from the ongoing AVALON study investigating stroke in PWH (NIH-1R21TW012384-01A1). Over 12 months (September 2024–August 2025), we included all PWH presenting with neuroimaging-confirmed acute/subacute stroke (imaging within three weeks of symptom onset) to Western Cape public sector hospitals with brain imaging facilities (n = 10). We identified 605 PWH with stroke. Median age was 44 years (interquartile range [IQR] 36–54), with 51% female at birth (Table 1). Ischaemic stroke comprised 85% of cases, mostly involving the middle cerebral artery territory (63%). Previous stroke (> 4 weeks before current) was evident in 17%. At presentation, 76% were on ART for a median 8.2 years (IQR 3.8–11.9), most commonly tenofovir/lamivudine/dolutegravir (73%). ART was initiated/reinitiated within six months prior to stroke in 24.4%, with a median of 68 days (IQR 26–119) from initiation/reinitiation to stroke. ART adherence derived from pharmacy refills was 57% in the preceding six months. The most recent median viral load was < 50 copies/mL (IQR < 20–6777), measured a median of 85 days (IQR 4–420) before stroke. We report the largest South African cohort of PWH with stroke to date. Participants were young, on currently recommended ART, and 28% had no comorbidities. A quarter initiated/reinitiated ART within six months of stroke, supporting previous reports suggesting a potential immune reconstitution-like syndrome.

The South African Family Practice is a peer-reviewed scientific journal, which strives to provide primary care physicians (and their teams), as well as researchers, with a broad range of scholarly work in the disciplines of family medicine, primary health care, rural medicine, district health and other related fields. SAFP publishes original research, clinical reviews, and pertinent commentary that advance the knowledge base of these disciplines.