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AbstractDuring sexual transmission, the large genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection1. Understanding the drivers of this bottleneck is crucial to develop effective infection control strategies2. Genetic characteristics of the potential founder viruses and events in the recipient partner are both known to contribute to this bottleneck, but little is understood about the importance of the source partner3. To test the hypothesis that the source partner affects the multiplicity of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results demonstrate the importance of infection stage of the source partner, and not exposure route, in determining founder variant multiplicity. Specifically, acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple variant transmission when compared with someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple founder strain infections and can inform clinical intervention study design and interpretation.

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