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

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.