PT - JOURNAL ARTICLE AU - David A. Rasmussen AU - Eduan Wilkinson AU - Alain Vandormael AU - Frank Tanser AU - Deenan Pillay AU - Tanja Stadler AU - Tulio de Oliveira TI - External introductions helped drive and sustain the high incidence of HIV-1 in rural KwaZulu-Natal, South Africa AID - 10.1101/119826 DP - 2017 Jan 01 TA - bioRxiv PG - 119826 4099 - http://biorxiv.org/content/early/2017/03/24/119826.short 4100 - http://biorxiv.org/content/early/2017/03/24/119826.full AB - Despite increasing access to antiretroviral therapy, HIV incidence in rural KwaZulu-Natal communities remains among the highest ever reported in Africa. While many epidemiological factors have been invoked to explain this high incidence, widespread human mobility and movement of viral lineages between geographic locations have implicated high rates of transmission across communities. High rates of crosscommunity transmission call into question how effective increasing local coverage of antiretroviral therapy will be at preventing new infections, especially if many new cases arise from external introductions. To help address this question, we use a new phylodynamic modeling approach to estimate both changes in epidemic dynamics through time and the relative contribution of local transmission versus external introductions to overall incidence from HIV-1 subtype C phylogenies. Our phylodynamic estimates of HIV prevalence and incidence are remarkably consistent with population-based surveillance data. Our analysis also reveals that early epidemic dynamics in this population were largely driven by a wave of external introductions. More recently, we estimate that anywhere between 20-60% of all new infections arise from external introductions from outside the local community. These results highlight the power of using phylodynamic methods to study generalized HIV epidemics and the growing need to consider larger-scale regional transmission dynamics above the level of local communities when designing and testing prevention strategies.