Tracking external introductions of HIV using phylodynamics reveals a major source of infections in rural KwaZulu-Natal, South Africa.

Despite increasing access to antiretrovirals, HIV incidence in rural KwaZulu-Natal remains among the highest ever reported in Africa. While many epidemiological factors have been invoked to explain such high incidence, widespread human mobility and viral movement suggest that transmission between communities may be a major source of new infections. High cross-community transmission rates call into question how effective increasing the coverage of antiretroviral therapy locally will be at preventing new infections, especially if many new cases arise from external introductions. To help address this question, we use a phylodynamic model to reconstruct epidemic dynamics and estimate the relative contribution of local transmission versus external introductions to overall incidence in KwaZulu-Natal from HIV-1 phylogenies. By comparing our results with population-based surveillance data, we show that we can reliably estimate incidence from viral phylogenies once viral movement in and out of the local population is accounted for. Our analysis reveals that early epidemic dynamics were largely driven by external introductions. More recently, we estimate that 35 per cent (95% confidence interval: 20-60%) of new infections arise from external introductions. These results highlight the growing need to consider larger-scale regional transmission dynamics when designing and testing prevention strategies.