P5340HIV-infected participants on combination ART (tenofovir, emtricitabine, efavirenz) have improved endothelial function and smaller retinal venular calibers compared to treatment naive participants
Authors: Strijdom H , Essop M F , Goswami N , De Boever P , Webster I , Everson F , Kamau F M , Charania S , Nawrot T S 
Published: October 2019

Abstract

Background
Cumulative data from several studies suggest that HIV-infected populations have a 2-fold increased cardiovascular risk. Evidence is also pointing to a link between HIV and early vascular changes, including endothelial dysfunction and subclinical atherosclerosis. There is a paucity of data from sub-Saharan Africa (the epicenter of the global HIV burden and a region with a rapidly increasing cardiovascular disease [CVD] incidence); furthermore, the contribution of specific combination ART (c-ART) regimens to HIV-related CVD and early vascular changes remain unclear.

Purpose
To investigate the association between HIV-infection, c-ART (TDF+FTC+EFV), CVD risk and vascular markers of CVD in an adult cohort in South Africa.

Methods
Cross-sectional study, participants assigned to 3 groups: HIV-free (HIV−), HIV-infected ART naïve (HIV+/−) and HIV-infected on ART (HIV+/+). Data collection: demographic information, anthropometrics, CVD risk factors, and blood chemistry. Vascular endpoints assessed: brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (C-IMT) and retinal microvascular calibers.

Results
Cohort size: n=427 (HIV− n=148; HIV+/− n=69; HIV+/+ n=210), mean age: 39.4 years, 68.9% females. Analysis of cardiovascular risk showed no differences in smoking and alcohol consumption, and blood pressure was unaffected by HIV-status. The untreated HIV group had a high % participants with clinically low HDL-cholesterol levels, whereas c-ART seemed to reduce the prevalence (HIV+/−: 58% vs 31% in HIV− and 26% in HIV+/+; p<0.01). Prevalence of hyper-LDL-cholesterolemia and hypertriglyceridemia were similar. High sensitivity CRP levels were unaffected by HIV-status. Markers of end-organ damage showed renal involvement in the HIV+ groups (median regression of urine albumin-creatinine ratio in HIV+/+ and HIV+/− vs HIV−: Beta±SEM: 0.5±0.3 and 0.8±0.2 in HIV+/+ and HIV+/− respectively, p=0.02; adjusted for age, gender and ethnicity), as well as hepatic injury in the treated group (gamma-GT in HIV+/+ vs HIV−: Beta±SEM: 23.3±4.4, p<0.01, adjustment as above). Multiple regression of vascular markers showed increased FMD in HIV+/+ vs HIV+/− (Beta±SEM: 1.8±0.8, p=0.01; adjusted for age, gender, ethnicity and BMI), and decreased central retinal venular equivalent (CRVE) in HIV+/+ vs HIV+/− (Beta±SEM: −11.9±3.8, p=0.002) and vs HIV− (Beta±SEM: −7.1±3.2, p=0.03), adjustment as above. Carotid IMT was not affected by HIV or treatment status.

Conclusions
Combination ART consisting of TDF+FTC+EFV conferred vascular protection in HIV-infected participants as shown by improved endothelial function (increased FMD) and smaller CRVE compared to ART naïve counterparts. There was no evidence of subclinical atherosclerosis involvement (C-IMT). The vasculoprotective effects in the treated group were supported by a favourable HDL-cholesterol profile, despite unchanged inflammation (hs-CRP), and evidence of renal and hepatic impairment.

Acknowledgement/Funding
Dept of Science and Technology (South Africa); National Research Foundation (South Africa); Belgian Science Policy, Belgium; Austrian Grants Agency.