Longitudinal cohort study of older-aged people living with HIV infection in southwestern Uganda and age and gender-matched HIV uninfected controls with the primary aim of measuring the epidemiology of cardiovascular and pulmonary disease in this study setting, and particularly the contribution of HIV infection to it.

This study recruits people living with HIV/AIDS (PLWH) aged 40 and older; and an HIV-uninfected age and gender-matched, community-based comparison group in the HIV clinic catchment area.

Study investigators will collect sociodemographic, clinical, immune activation, systemic inflammation, plasma and stool microbiome, and clinical pulmonary and cardiovascular disease measures. Our outcomes of interest are measures of carotid atherosclerosis, including carotid intima media thickness and presence of plaque, prior ischemic heart disease (as measured by electrocardiograms), peripheral arterial disease (as measured by ankle-branchial index), and lung function as measured by pulmonary function testing. Our exposures of interest are traditional cardiovascular disease risk factors (e.g. age, gender, family history of cardiovascular disease, smoking history, diet, activity, body mass index, prevalence of diabetes, and prevalence of hypertension) and HIV-related cardiovascular risk factors (e.g. nadir CD4 count, ART duration and regimen, gut and plasma microbiome composition, and markers of both immune activation and systemic inflammation).

Investigators will collect this data to accomplish the following aims:

Aim 1: Compare the prevalence of atherosclerosis, measured by cIMT, ankle-brachial index, and presence of q-waves on electrocardiogram, in PLWH taking ART aged 40 and older and age and gender-matched, population-based HIV-uninfected controls. This study aims to be among the first to capture high-quality measures of atherosclerotic disease among a population of PLWH in sub-Saharan Africa. The study aims to test the hypothesis that older-age Ugandans on ART will have thicker carotid intima media, higher prevalence of peripheral arterial disease, and higher prevalence of pathologic q-waves on electrocardiogram than age and gender-matched, HIV-uninfected controls.

Aim 2: Evaluate correlates of atherosclerosis in older-age PLWH on ART, including both traditional (age, gender, smoking, diabetes and hypertension prevalence) and HIV-related risk factors (immune activation, systemic inflammation, and stool and plasma microbiome composition). The study will leverage a collaboration with the Ragon Institute to perform immunologic and molecular testing for microbial translocation and markers of immune activation and systemic inflammation (e.g. soluble CD163, C-reactive protein, IL-6, CD8+ T-lymphocyte activation).

Aim 3: Compare the progression of atherosclerosis in PLWH versus HIV-uninfected individuals over five years of observation time. The study aims to test the hypothesis that the rate of change in carotid intima media thickness will be faster in among PLWH over 45 on ART than age and gender-matched HIV-uninfected controls, and that rates of change in carotid intima media thickness among the HIV-infected cohort will be associated with markers of microbial translocation, immune activation, and systemic inflammation.

Aim 4: Compare the prevalence and incidence of abnormal pulmonary function (FEV1, FVC, FEV1/FVC) in PLWH on ART and age- and gender-matched, population-based HIV-uninfected controls, utilizing handheld spirometry with bronchodilator challenge. The study aims to test the hypothesis that pulmonary function is worse and COPD is more common among people living with HIV/AIDS than age- and gender-match HIV-uninfected controls.

Group 1 Inclusion Criteria:

• HIV infected
• Age > 40 years old at enrollment
• Minimum 2 years of antiretroviral therapy

Group 1 Exclusion Criteria:

• Decline informed consent

Group 2 Inclusion Criteria:

• Living in catchment area of Mbarara Regional Referral Hospital (greater Mbarara)
• Age > 40 years old
• Age and gender matched to a participant in group 1

Group 2 Exclusion Criteria:

• HIV infection (tested annually as part of study procedures)
• Decline informed consent

The study recruits two sub-groups of participants:

Study Group 1:

-HIV infected persons aged 40 and older, in care at the Immune Suppression Syndrome HIV Clinic at Mbarara Regional Referral Hospital

Study Group 2:

-Community-based, HIV uninfected persons recruited from the catchment area of the Mbarara Regional Referral Hospital (greater Mbarara), and age and gender-matched to Group 1 participants