The Rakai Community Cohort Study (RCCS) is an open cohort of ~15,800 persons, 15-49 in 50 communities in rural Rakai, Uganda (HIV prevalence ~12.3%, incidence ~1.0/100 py.) Using partnership-based transmission models, we estimate that 40% of annual transmissions are due to extra-household partners of whom ~62% are from known partners outside an individual's community of residence (i.e., extra-community contacts seed infections into the general population.) The sources of these infections are largely unknown. In 2011-13, surveillance was extended to key communities including fishing communities (HIV prevalence 35-43%, incidence ~3.9/100 py) and transport hubs. With PEPFAR support, the Program will scale up combination HIV prevention (CHP) using antiretroviral therapy, male circumcision, prevention of mother-to-child HIV transmission and demand creation/behavioral modification in Rakai District (population ~400,000). We will test the hypotheses that: i) Key communities seed infection into the general RCCS population, and ii) that CHP will reduce HIV incidence through changing transmission dynamics within and between the general rural and key populations.
Aim 1 will assess transmission dynamics in and between general and key communities prior to CHP scale-up (2011-13). The spatial scale of sexual networks will be assessed using household GPS, location of partners and mobility. Phylogenetic analyses (Sanger sequencing of gag and env) will assess patterns, timing and directionality of HIV transmission. Transmission modeling based on sexual partner and phylogenetic data will quantify the proportions of transmissions occurring within and between general and key communities. This addresses hypothesis 1, and provides the counterfactual for CHP Impact Evaluation.
Aim 2 will assess HIV incidence and transmission dynamics during scale up of CHP services (2013-17.) CHP coverage will be monitored. The hazard ratio of population-level HIV incidence associated with community CHP coverage and individual risk characteristics will quantify the impact of CHP. The study is powered to detect an expected 46% reduction in HIV incidence. Changes in transmission dynamics will be assessed by the methods for Aim 1. Results will inform CHP programs in rural Africa.

Public Health Relevance

In Uganda's predominantly rural populations the HIV epidemic may be driven by introduced infections from high risk communities. We will determine sources of HIV infections in the agrarian population (2011-13), and evaluate scaled up combination HIV prevention using proven efficacious interventions (2013-17). Evaluation will assess service coverage and impact on HIV incidence, with an expected reduction of 46%. Results will guide CHP scale up in rural Africa.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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AIDS Clinical Studies and Epidemiology Study Section (ACE)
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Bacon, Melanie C
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Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
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Grabowski, Mary K; Reynolds, Steven J; Kagaayi, Joseph et al. (2018) The validity of self-reported antiretroviral use in persons living with HIV: a population-based study. AIDS 32:363-369
Kankaka, Edward Nelson; Ssekasanvu, Joseph; Prodger, Jessica et al. (2018) Sexual risk behaviors following circumcision among HIV-positive men in Rakai, Uganda. AIDS Care 30:990-996
Olawore, Oluwasolape; Tobian, Aaron A R; Kagaayi, Joseph et al. (2018) Migration and risk of HIV acquisition in Rakai, Uganda: a population-based cohort study. Lancet HIV 5:e181-e189
Billioux, Veena G; Grabowski, Mary K; Ssekasanvu, Joseph et al. (2018) HIV viral suppression and geospatial patterns of HIV antiretroviral therapy treatment facility use in Rakai, Uganda. AIDS 32:819-824
Mwinnyaa, George; Gray, Ronald H; Grabowski, Mary K et al. (2018) Brief Report: Age-Disparate Relationships and HIV Prevalence Among Never Married Women in Rakai, Uganda. J Acquir Immune Defic Syndr 79:430-434
Seremba, Emmanuel; Ssempijja, Victor; Kalibbala, Sarah et al. (2017) Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda. AIDS 31:781-786
Abassi, Mahsa; Morawski, Bozena M; Nakigozi, Gertrude et al. (2017) Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda. J Neurovirol 23:369-375
Grabowski, M Kate; Serwadda, David M; Gray, Ronald H et al. (2017) HIV Prevention Efforts and Incidence of HIV in Uganda. N Engl J Med 377:2154-2166
Chang, Larry W; Grabowski, Mary K; Ssekubugu, Robert et al. (2016) Heterogeneity of the HIV epidemic in agrarian, trading, and fishing communities in Rakai, Uganda: an observational epidemiological study. Lancet HIV 3:e388-e396