Predicting Early Cardiovascular Risk among HIV-Infected and Uninfected Kenyan Adults

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ABSTRACT Despite the high prevalence of HIV in sub-Saharan Africa, cardiovascular disease (CVD) is the leading cause of morbidity and mortality in this region. Predictors of CVD are well-established in resource-rich countries, but whether these same risk factors are strongly associated with CVD in sub-Saharan Africa is not known. Growing evidence from the US and Europe suggests that HIV itself may be a risk factor for CVD, through a combination of medication side effects, inflammation and immune activation, but how HIV disease and treatment impacts CVD risk in Kenya and other countries with generalized HIV epidemics is less well studied. The overall goal of this proposal is to determine the prevalence of traditional and non-traditional risk factors for CVD in HIV-infected and uninfected men and women in western Kenya. Metabolic risk factors include hyperlipidemia, glucose intolerance and obesity, which when taken together define a metabolic syndrome (MetS) that has been associated with myocardial infarction and stroke in high-income countries. This will be the focus of the first aim. In the second aim, we determine prevalence and predictors of chronic inflammation and immune activation, comparing risk factor prevalence among HIV-infected and uninfected and defining contributions of high HIV RNA levels, antiretroviral use, and other HIV-specific risk factors among those with HIV. In our third aim, we define rates of subclinical atherosclerosis among these Kenyan adults using high resolution ultrasound to measure carotid intima media thickness (C-IMT). Our multidisciplinary team from the University of Washington (UW), University of Nairobi, Kenyatta National Hospital and the Kenya Ministry of Health will conduct this cross-sectional study of 600 participants, 300 of whom will be HIV-infected, in a part of Kenya where >10% of the adult population is infected with HIV. We will leverage 30 years of experience doing research and training in Kenya, and 10 years implementing studies in the Kisumu District Hospital and surrounding community, to identify young and middle aged individuals with CVD risk factors and abnormal C- IMT. HIV-infected men and women >30 years old will be recruited from HIV clinics and uninfected participants at voluntary HIV testing sites and through outreach to partners. During a single follow-up visit, an interview, blood draw, and carotid ultrasound will be performed; assays will be conducted at a local research laboratory (glucose, lipids) and UW (Interleukin-6, highly sensitive C-reactive protein). This exploratory R21 application is innovative in its use of new technologies to assess C-IMT in HIV-infected and uninfected Kenyans. It will lay a solid foundation for expanding our established research infrastructure into research on CVD and non- communicable diseases by significantly advancing our understanding of subclinical atherosclerosis and how risk is modulated by HIV, metabolic risk factors, inflammation and immune activation. These data will be critical to developing targeted, feasible intervention trials to combat CVD in sub-Saharan Africa over the next decade.