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Scaling HIV prevention from individuals to populations is hard. We are not short of efficacious tools, condoms, male circumcision, early antiretroviral therapy and pre-exposure prophylaxis chief among them. However, three recent African cluster randomised trials of different combinations of these tools (TasP, Search and Ya Tse) have reported disappointing results, demonstrating that achieving population effectiveness remains difficult. The largest of these trials - HPTN 071 (PopART) - will report in March 2019. Population-level incidence of HIV remains high in many settings. Definitive answers as to what works and why remain elusive. In this seminar, I will present work on the HPTN 071 (PopART) trial, and introduce the PANGEA-HIV consortium. PANGEA brings together six leading HIV epidemiology groups in sub-Saharan Africa. I will present new sequencing, phylogenetic and modelling tools that my collaborators and I have been developing. Combined together, these tools are identifying heterogeneities in transmission that could be exploited for better prevention.