The age and sex dynamics of heterosexual HIV transmission in Zambia: an HPTN 071 (PopART) phylogenetic and modelling study

While much progress has been made in reducing the incidence of HIV-1 infection in sub-Saharan Africa in recent years, bringing the epidemic to an end will require identification of the demographic groups that continue to contribute to transmission. Pathogen phylogenetics and individual-based mathematical models (IBMs) of transmission are approaches that enable researchers to explore such questions. Here, we used both methods to characterise the ages and sexes of the individuals involved in heterosexual transmission in the context of the HPTN 071 (PopART) trial in Zambia. The results were concordant, and show that the male partner was on average older than the female by less than seven years, with larger age gaps in male-to-female than female-to-male transmissions. We found that the largest gaps for female recipients were amongst the youngest of those recipients. Conversely, the youngest male recipients saw the smallest gaps. We further used the IBM to demonstrate that transmission to new age cohorts first entering into sexual activity is driven predominantly by male-to-female transmission. We also simulated the PopART universal testing and treatment intervention into the future to show that effective treatment of under-35-year-olds accounts for 93.8% of the reduction in incidence by 2039, while effective treatment of under-35-year-old men accounts for 62.1%. Finally, we simulated a one-year cessation of ART treatment for the whole population, which resulted in an immediate increase in the average age at transmission of both sources and recipients. With it becoming ever more expensive and difficult to find treatment-naive individuals and link them to care, targeted interventions for demographic groups such as under-35 men may be the key to finally ending HIV.