PROJECT SUMMARY/ABSTRACT The global burden of HIV associated cardiovascular disease (CVD) has tripled over the last two decades with the majority of the burden experienced in sub-Saharan Africa (SSA). Reducing the burden of CVD in this population will require a firm understanding of region-specific risk factors, particularly those known to modulate the inflammatory response involved in CVD. Although alteration of the gut bacteria communities (dysbiosis) has been linked to CVD in healthy adults, the role of gut dysbiosis on CVD risk is not well investigated among HIV-infected patients receiving suppressive ART. This K01 proposal details a five-year plan to provide the candidate, Dr. Tecla Temu, with the training and expertise needed to evaluate the relationship between gut dysbiosis and markers of early CVD in an established cohort of HIV-infected adults enrolled in the Kenya HIV- CVD study (R21 TW010459; PI: Farquhar). Taking advantage of stool specimens, archived blood samples, extensive data on HIV-infection related factors, co-infections (latent TB, helminths), and measures of early atherosclerotic disease (carotid intima media thickness) and metabolic disease in the Kenya HIV-CVD study, this project proposes to 1) characterize gut microbiota of HIV-infected adults in SSA and 2) determine the relationship of gut microbiota with measures of inflammation and subclinical CVD. Dr. Temu's long-term goal is to be a successful physician-scientist and independent investigator focused on understanding the pathogenesis of HIV-associated CVD in resource-limited settings. She aims to develop new preventive and therapeutic methods that will improve the health of disadvantaged, underserved populations in SSA and globally. The proposed program will build on the candidate's extensive experience with international clinical and laboratory research and improve her skills in cardiovascular research, specifically study design, as well as analysis and interpretation of microbiome data, and HIV mucosal immunology. Dr. Temu has strong institutional support from the University of Washington's Department of Global Health where she is currently a Clinical Assistant Professor. Her training plan incorporates an outstanding mentoring environment, one that includes experts in HIV, cardiovascular disease, and gut microbiome research in SSA, and it leverages more than 30 years of Fogarty-funded research and training collaborations between the University of Washington and University of Nairobi. This highly supportive environment will enable Dr. Temu to not only accomplish her proposed research and training goals and successfully position herself for an independent research career, but also allow her to achieve her full potential for productivity and creativity as a physician-scientist in the UW Department of Global Health.