# Epidemiology of coronary artery disease among people with HIV in rural sub-Saharan Africa

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $759,919

## Abstract

ABSTRACT
More than $50 billion has been invested to expand access to antiretroviral therapy (ART) for people living with
HIV (PLWH) in sub-Saharan Africa. Yet, regional HIV programs largely overlook causes of non-AIDS morbidity,
thereby threatening to undermine the tremendous gains achieved. In the US, coronary artery disease (CAD) is
significantly more common among PLWH than HIV-uninfected individuals. However, determinants of CAD
among PLWH in the US are unlikely to generalize to rural Africa, due to unique environmental, inflammatory,
and social risk factors. For example, in an NHLBI R21-funded pilot, we enrolled a cohort of PLWH on ART in
rural Uganda and population-based, HIV-negative controls, and demonstrated that PLWH have greater rates of
arterial stiffness and electrocardiographic abnormalities despite having lower blood pressure, lower low density
lipoprotein and lower rates of active smoking. We also identified inflammatory pathways in Uganda, such as
the kynurenine:tryptophan ratio, which differ by sex, and correlate more strongly with atherosclerosis and
mortality in Uganda than the US. We now propose to augment our established research infrastructure with
contrast enhanced computed tomography of the coronary arteries, to directly and non-invasively measure the
impact of HIV on CAD in rural Uganda, and identify regional determinants of CAD through the following aims:
 Aim 1: Determine whether CAD is more prevalent and severe among PLWH than HIV-uninfected
comparators in rural Uganda. We will complete coronary CT angiography in 600 participants, and compare
the prevalence and severity of CAD between PLWH and HIV uninfected comparators. Hypothesis: PLWH in
Uganda have a higher prevalence and severity of CAD compared to HIV-uninfected comparators.
 Aim 2: Determine the extent to which the association between HIV infection and CAD is
modified by sex and region. Within our cohort, we will test for effect modification by sex (Aim 2a). Then, by
pooling our data with US data from PLWH enrolled in the REPREIVE study, we will test for effect modification
by country of origin (Aim 2b). Hypothesis: The association between HIV infection and CAD is greater among
women (vs. men) and among PLWH in Uganda (vs. PLWH in the US).
 Aim 3: Identify regional correlates of CAD, and develop a risk prediction score for the presence
of CAD among PLWH in rural sub-Saharan Africa. We will collect data on traditional (e.g. age, smoking,
diabetes), HIV-specific (e.g. macrophage activation, CD4 count, ART history), and region-specific factors (e.g.
biomass exposure, tuberculosis history, K:T ratio). In Aim 3a we will include traditional, HIV-specific and
regional risk factors in models to identify correlates of CAD. In Aim 3b, we will propose a simplified risk score to
identify PLWH with CAD. Hypothesis: Non-traditional risk factors provide substantive explanatory power for
estimating CAD risk beyond traditional factors typically used in risk prediction models in ...

## Key facts

- **NIH application ID:** 10169499
- **Project number:** 5R01HL141053-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** MARK J SIEDNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $759,919
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169499

## Citation

> US National Institutes of Health, RePORTER application 10169499, Epidemiology of coronary artery disease among people with HIV in rural sub-Saharan Africa (5R01HL141053-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10169499. Licensed CC0.

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