Moderately age-disparate relationships dominate phylogenetically linked pairs involving young women with HIV in KwaZulu-Natal, South Africa

Abstract BACKGROUND Young women aged 15–24 bear a disproportionate burden of new HIV infections in sub-Saharan Africa. Age-disparate relationships with older men have been proposed as a major contributor to this pattern. METHODS We conducted whole-genome sequencing of HIV in large cohort of individuals in KwaZulu-Natal, South Africa, (the Vukuzazi cohort). Samples with viral loads >50 copies/ml were sequenced. Genomes passing quality control were grouped into clusters using maximum-likelihood phylogenetic analysis. Potential transmission pairs were analysed alongside participant age and sex data. A Bayesian random-effects model estimated transmission rates between demographic groups while accounting for population age–sex structure. FINDINGS Among 18,025 participants enrolled 2018–2020, 6,096 were HIV-positive. Sequencing yielded 1,097 genomes, identifying 89 clusters containing 205 individuals and 73 likely male–female linked phylogenetic pairs. Across pairs, men were a median of 5 years older than women (IQR −1, 12). Women <30 years paired with men a median of 7 years older, whereas among women ≥30 years men were typically younger. After accounting for population structure, the strongest signal for transmission was between women aged 25–29 and men up to four years older. CONCLUSIONS Relative transmission rates were greatest with moderate age differences. Large intergenerational age gaps were not dominant.