Cardiovascular disease risk among people living with HIV in South Central Uganda

Sammanfattning: Background: With the introduction of effective antiretroviral therapy (ART), the clinical management needs of people living with HIV are rapidly shifting from AIDS-related opportunistic infections to age-related co-morbidities. Research from high-income countries has demonstrated that people living with HIV are at an increased risk for developing cardiovascular disease (CVD) due to a combination of increased traditional CVD risk factors, HIV infection, and ART use. However, limited population-based data are available from Sub- Saharan Africa despite being home to close to 70% of the global people living with HIV population. This PhD thesis aimed to generate population-based data on the burden of CVD risk factors in people living with HIV among participants aged 35 to 49 in South Central Uganda to subsequently provide CVD-related epidemiological insights to inform HIV-related care services. Methods: Studies I-III are based on a cross-sectional study that collected data in 37 non- fishing communities among participants aged 35 to 49 years as part of the 18th survey round of the Rakia Community Cohort Study (RCCS) in South Central Uganda. Study IV is based on a pilot study that collected cross-sectional data in five non-fishing communities between October 2018 and January 2019 as part of the 19th survey round of the RCCS. Study I included a total of 1,968 participants (990 participants living with HIV and 978 HIV-negative participants), study II 423 participants living with HIV, and 1,463 participants (759 participants living with HIV and 704 HIV-negative participants) in study III. For study IV, a total of 118 participants were included, 34 participants living with HIV and 33 HIV-negative participants aged 35 to 49, and 23 participants living with HIV and 28 HIV-negative participants aged 50 and older. Differences in CVD risk factors explored by HIV status included lifestyle CVD risk factors, anthropometric risk factors, and physiological risk factors of hyperglycemia, hypertension, and dyslipidemia in study I, Non-alcoholic fatty liver disease (NAFLD) in study III, and Electrocardiogram (ECG) abnormalities and arterial stiffness in study IV. In addition, differences by HIV status in CVD and type 2 diabetes risk scores were explored in study I. Finally, the associations between untreated diagnosed HIV and ART use to metabolic syndrome were explored in study II. Results: In study I, people living with HIV presented with lower overall obesity (6% vs. 12%, p < .001), lower abdominal obesity (12% vs. 18%, p < .001), and dyslipidemia (54% vs. 72%, p < .001) as compared to HIV-negative participants. A positive HIV status was found to be associated with a lower odds of low high-density (HDL) [defined as <1.03 mmol/L in men and < 1.29 mmol/L in women] (odds ratio (OR) = 0.43, 95% Confidence Interval (CI): 0.35- 0.52). No difference by HIV status was found in CVD or type 2 diabetes risk scores. In study II, duration of ART use was found to be negatively associated with low HDL, with an adjusted OR of 0.87 per one-year increase (95% CI: 0.82-0.93). Female sex (OR = 4.87, 95% CI: 2.98-7.97) and alcohol consumption (OR = 2.29, 95% CI: 1.47-3.59) were additionally found to be associated with increased odds of low HDL. In study III, participants with HIV were found to have a comparable prevalence of NAFLD as compared to HIV-negative participants (13% vs. 11%, p = .17) and HIV infection was found not to be associated with NAFLD. In study IV, no differences were found in ECG abnormalities by HIV status in either the 35 to 49 or 50 and older age groups. Arterial stiffness, at the 11 m/s cutoff, p = .03, was found to be more common among participants living with HIV as compared to HIV- negative participants in the 35 to 49 population. Conclusion: The findings of this thesis point to people living with HIV presenting with a more favorable CVD risk factor profile, including NAFLD and ECG abnormalities, as compared to HIV-negative participants. There is however some evidence that arterial stiffness is more prevalent in people living with HIV aged 35 to 49. In addition, ART use, particularly first-line regimen, may offer a protective CVD risk factor benefit by reducing the odds of low HDL by 13% with each increasing year of reported ART use. Finally, females living with HIV presented with higher overall obesity and abdominal obesity rates as compared to males, and both overall obesity and abdominal obesity were found to be associated with hyperglycemia, hypertension, and dyslipidemia. This identifies a possible area in which HIV-related care services can target with CVD reduction prevention efforts.