Structural Cardiac Abnormalities, Ventricular Dysfunction Phenotypes, and Heart Failure Risk among Antiretroviral Therapy-treated People Living with HIV in South Africa

Background

The manifestations of cardiovascular disease (CVD) among people with HIV (PWH) differ by region globally. While HIV disease is associated with increased atherosclerotic CVD risk in the global North, non-ischemic heart failure (HF) is more common in sub-Saharan Africa, the global HIV epicenter. We estimated the effect of treated HIV on the frequency and phenotype of HF and its cardiac precursors in South Africa (SA).

Methods

In an observational study, we recruited PWH on antiretroviral therapy (ART), age ≥40 years and people without HIV (PWoH) with similar distributions of age, sex, ethnicity, and hypertension, from a community clinic in Khayelitsha (Cape Town, SA). Procedures included a clinical assessment, echocardiography (Echo), and b-type natriuretic peptide (BNP) measure. Echo parameters defined structural abnormalities, left ventricle (LV) filling pressure, and LV systolic and diastolic dysfunction (DD). HF was defined by symptoms and/or BNP ≥35pg/mL and LV dysfunction, subcategorized as reduced, mildly reduced, or preserved ejection fraction (HFrEF, HFmrEF, and HFpEF). Comparisons by HIV status were adjusted for age, sex, hypertension, smoking, obesity, diabetes, elevated LDL-cholesterol, and hazardous alcohol use.

Results

Between September 2022 and August 2025, we enrolled 1008 PWH and 500 controls [median (Q1-Q3) age 48 years (43-53), 77% female]. Among PWH and controls respectively, 37% and 39% had hypertension, 21% and 25% were current smokers, 40% and 45% were obese, and 9% and 17% had diabetes. LV systolic dysfunction (1%) and HFrEF (1%) were rare, and undiagnosed HFpEF (8%) was the predominant HF phenotype. Compared to controls, PWH had higher odds of elevated LV mass index (LVMI) (OR 2.1; 95%CI 1.5-3.0) and DD (OR 1.4; 95%CI 1.0-2.0). Risk for elevated LVMI and DD was greatest among women with HIV, who also had an increased risk for undiagnosed HFpEF (OR 1.9; 95%CI 1.2-3.2), compared to women without HIV; effects which were not seen among men (p=0.051 for HIV*Sex interaction).

Conclusions

In a peri-urban SA community with a high burden of cardiometabolic risk factors, the frequency of abnormal structural and functional cardiac precursors of HFpEF was greater amongst ART-treated PWH. This was most pronounced amongst women with HIV, who also had increased risk of undiagnosed HFpEF.

Clinical Perspective

1) What is new? (maximum 100 words, formatted as 2-3 bullets)

• In this community with a high prevalence of HIV, tuberculosis, and cardiometabolic risk factors, heart failure (HF) frequency (10%) was high and dominated by preserved ejection fraction (HFpEF) (8%).

• Echocardiographic defined structural and functional precursors of HFpEF were comparatively more frequent in people with HIV,

• Women with HIV were at highest risk of HFpEF.

2) What are the clinical implications? (maximum 100 words, formatted as 2-3 bullets).

• There is a need for resource efficient tools for screening and early detection of HFpEF in primary care clinics serving similar communities.

• The relationship between HIV, sex, and adiposity in HFpEF pathogenesis needs further study.