PROJECT SUMMARY As HIV prevention and treatment efforts are successfully scaling up, life expectancies of individuals living with HIV are approaching to that in the general population. In rural KwaZulu-Natal, South Africa, where adult HIV prevalence exceeds 20%, a growing proportion of individuals living with HIV are aged over 50 years, putting them at the risk of developing age-associated co-morbidities. To ensure effective screening, diagnosis, and treatment efforts for HIV, TB and associated non-communicable diseases (NCDs), a comprehensive understanding of the disease drivers and distribution, as well as the interactive mechanisms of the co- epidemics among people living with HIV will be critical in sub-Saharan Africa (SSA). Our overarching goal in this project is to quantify the overlap in the infectious (HIV and TB) and non- communicable disease (hypertension, diabetes and obesity) epidemics and to determine their key individual, familial, household, and geospatial risk factors to ultimately design an effective and efficient care delivery model relevant to the overlapping epidemics in SSA. The project will take advantage of one of the largest ongoing population-based HIV cohorts in the world – the Africa Health Research Institute’s population cohort. Vukuzazi ("Wake up and know ourselves" in isiZulu), a multi-omics population science platform was established in 2018 to add comprehensive health phenotyping for multiple diseases, including HIV, TB, and diabetes, hypertension and diabetes to the ongoing longitudinal population surveillance platform. In light of the syndemic theory framework, the project will leverage the fully integrated data from both research platforms and utilize multilevel and spatial-temporal modelling to understand the interactive mechanisms and spatial distribution of the co-epidemics. The epidemiological and spatial understanding of the co-epidemics will also provide an opportunity to inform development of a co-care delivery model for integration of NCD care into HIV/TB co-delivery models in a HIV hyperendemic rural African setting. Building on one of the world’s largest ongoing population-based cohorts, the project will bring together a team of investigators with diverse and complementary areas of expertise to establish a multilevel analytical, methodological, and theoretical framework to address the emerging multimorbidity epidemic in South Africa and other similar settings in SSA. This framework will be co-developed by US, UK and South African investigators and trainees and will significantly enhance local capacity. Results from this study will be among the first to disentangle the complex associations between the individual, familial, household and community factors that impact HIV, TB and NCD risk in one of the world’s most severely affected populations. The results of the project will provide critical information for the design of an effective and efficient co-care delivery model for HIV and associated co-epidemics in rural SSA settings.

PROJECT NARRATIVE In the era of universal testing and treatment, a growing proportion of individuals living with HIV are over 50 years of age, putting them at the risk of developing age-associated non-communicable diseases (NCDs). By utilizing the comprehensive, integrated and geo-located data from the African Health Research Institute's population-based HIV cohort in rural KwaZulu-Nata, South Africa, this proposal seeks to fundamentally understand the spatial distribution and key individual, familial, household, community, and geospatial determinants associated with the overlapping burdens of HIV, TB, and NCDs to inform the development of effective and efficient health care delivery strategies.