Cardiovascular Disease among HIV-positive and HIV-negative Kenyan Adults

Abstract

Over half of the people living with HIV (PLHIV) reside in Eastern and Southern Africa where cardiovascular related mortality has continued to increase in the past decade. Data from high income countries estimates that PLHIV have shown an estimated 2-fold increased risk of cardiovascular disease (CVD) compared to HIV-negative individuals. This may be the result of traditional risk factors, including smoking, hypertension, unhealthy diets and lack of physical activity. It may also be as result of inflammation due to HIV or the use of antiretroviral therapy (ART) that has been associated with dyslipidemia, insulin resistance, and glucose intolerance, which frequently manifest as metabolic syndrome (MetS), a significant predictor of CVD. Despite increasing concerns of elevated risk of CVD among PLHIV, there is limited data on CVD risk factors, metabolic syndrome, the role of inflammation and the cost of CVD screening in sub-Saharan Africa (SSA). Data comparing people living with and without HIV infection are especially limited. To fill the knowledge gap, we conducted a study that compares cardiovascular risk among HIV-positive and HIV-negative Kenyan adults in Western Kenya. This dissertation compares the burden of cardiovascular disease risk factors among HIV-positive and HIV negative adults, examines the relationship between inflammation and these risk factors, and determines the cost of introducing CVD screening in health settings in Kenya. The first aim was to determine the prevalence and predictors of MetS and its individual components (hypertension, diabetes, elevated triglycerides, low HDL cholesterol, and abdominal obesity) and to compare risk profiles using the atherosclerotic CVD (ASCVD) risk score among 300 HIV-positive and 300 HIV-negative Kenyan adults in Western Kenya. We hypothesized that HIV-positive adults would have a higher prevalence of MetS and a higher ASCVD risk profile compared to HIV-negative individuals. The second aim was to compare immune activation and inflammatory markers that have been associated with increased CVD risk among HIV-positive and HIV-negative Kenyan adults in Western Kenya. We hypothesized that inflammatory markers, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hsCRP) would be higher among HIV-positive individuals when compared to HIV-negative individuals. The third aim was to estimate the incremental costs of integrating cardiovascular disease screening into on-going outpatient and HIV services in Kisumu County Hospital in Kenya. In the first aim, we conducted a cross-sectional study among adults ≥30 years of age with and without HIV infection seeking care at Kisumu County Hospital. Participants completed a health questionnaire and vital signs, anthropomorphic measurements, and blood for fasting blood glucose and lipids were obtained. MetS was defined using 2009 Consensus Criteria and the 10-year Atherosclerotic CVD (ASCVD) risk score was calculated using the Pooled Cohort Equation as outlined in the 2019 American College of Cardiology (ACC) / American Heart Association (AHA) Guideline on the Primary Prevention of Cardiovascular Disease. MetS prevalence was high in both HIV-positive and HIV-negative adults in western Kenya (1 in 20 and 1 in 10, respectively). Importantly, PLHIV were less likely to have MetS and had lower ASCVD risk scores than HIV-negative participants. In the second aim, using a multiplex immunoassay, we measured IL-1β, IL-6, TNF-α, and hsCRP concentrations among the same participants. We found higher levels of inflammatory markers (IL-1β, IL-6, TNF-α, and hsCRP) among PLHIV compared to HIV-negative participants. The majority of PLHIV were virally suppressed and higher concentrations among PLHIV persisted even after adjusting for traditional risk CVD factors, including dyslipidemia, obesity, diabetes and smoking. In the third aim, using a societal perspective, we conducted a micro costing study using time-in-motion measurements and semi-structured questionnaires to assess the direct medical costs, direct non-medical costs and indirect costs of CVD screening. The incremental cost of CVD screening for diabetes, hypertension and dyslipidemia was estimated at $35 per person and this was reduced by 40% to $21 if we adopted a high-risk screening scenario. Laboratory supplies were the main cost driver, accounting for 74% of this cost. Together these findings emphasize the need for CVD risk assessment among people living with and without HIV infection and the importance of further longitudinal studies to determine those risk factors that are most predictive of CVD events. We found CVD screening to be feasible, but the cost could be further reduced through global negotiations for more affordable laboratory testing options. We anticipate that this dissertation work will inform future studies of CVD among PLHIV and in pushing forward the policy initiatives on CVD screening in countries of sub-Saharan Africa.