Phylodynamic Structure in the Botswana HIV Epidemic

Background Studying viral sequences can provide insights into the structure of host contact networks through which the virus is transmitted. Uncovering the population structure of the HIV-1 epidemic in Botswana will help optimise public health interventions and may identify hidden sub-epidemics. We sought to determine the phylodynamic structure of the Botswana HIV-1 epidemic from viral sequence genetic data. Methods The Botswana Combination Prevention Project (BCPP) randomly sampled 20% of households in 30 villages in Botswana between 2013–2018 and tested for HIV-1. Extensive demographic data were collected from all participants and next-generation full-genome HIV-1 sequences were generated from HIV-1 positive participants (n = 4,164), 78% of whom were on antiretroviral treatment (ART). We inferred the stage of infection (< or > 1 year) among HIV-1 cases based on nucleotide diversity and clinical data using a previously trained machine learning model. We then reconstructed time-resolved gag and pol phylogenies from sequences, other Botswana cohorts and publicly available sequences that were genetically close to those from Botswana. We statistically explored phylogenies for partitions with diverging patterns of coalescence, indicating sub-epidemics, and estimated viral effective population size through time, a measure of viral incidence, for each partition. Finally, we compared the demographic makeup, clinical and geographic characteristics across partitions using χ2, ANOVA tests and Tukey analysis. Results We identified three partitions of time-resolved gag and pol phylogenies, revealing divergent patterns of coalescence and HIV-1 transmission. In both gag and pol phylogenies, partitions with persistent growth and transmission were characterised by lower treatment coverage and more recent infections when compared to other partitions. The Southern and South East regions of Botswana were over-represented in the fast-growing partitions. Conclusion Our findings suggest that transmission is slowing in segments of the population that have high ART coverage. However, recent infections are over-represented in ongoing sub-epidemics. The phylodynamic structure suggests that there are districts with higher growth and prioritising these in the deployment of public health interventions might curb new infections. Nonetheless the high mobility of Botswana residents should be taken into consideration in implementing effective interventions to combat HIV-1.