Analysis of the history and spread of HIV-1 in Uganda using phylodynamics

Abstract

HIV prevalence has decreased in Uganda since the 1990s, but remains substantial within high-risk groups. Here, we reconstruct the history and spread of HIV subtypes A1 and D in Uganda and explore the transmission dynamics in high-risk populations. We analysed HIV pol sequences from female sex workers in Kampala (n = 42), Lake Victoria fisher-folk (n = 46) and a rural clinical cohort (n = 74), together with publicly available sequences from adjacent regions in Uganda (n = 412) and newly generated sequences from samples taken in Kampala in 1986 (n = 12). Of the sequences from the three Ugandan populations, 60 (37.1 %) were classified as subtype D, 54 (33.3 %) as subtype A1, 31 (19.1 %) as A1/D recombinants, six (3.7 %) as subtype C, one (0.6 %) as subtype G and 10 (6.2 %) as other recombinants. Among the A1/D recombinants we identified a new candidate circulating recombinant form. Phylodynamic and phylogeographic analyses using BEAST indicated that the Ugandan epidemics originated in 1960 (1950-1968) for subtype A1 and 1973 (1970-1977) for D, in rural south-western Uganda with subsequent spread to Kampala. They also showed extensive interconnection with adjacent countries. The sequence analysis shows both epidemics grew exponentially during the 1970s-1980s and decreased from 1992, which agrees with HIV prevalence reports in Uganda. Inclusion of sequences from the 1980s indicated the origin of both epidemics was more recent than expected and substantially narrowed the confidence intervals in comparison to previous estimates. We identified three transmission clusters and ten pairs, none of them including patients from different populations, suggesting active transmission within a structured transmission network.

Fig. 1.. (a) Three clusters identified among 162 HIV-infected individuals. (b) Complete A/D recombinant lineage identified through possession of common breakpoints. Clusters were defined using a maximum pairwise genetic distance of 1.5 %. Subtype assignations are indicated in the panel on the right (between position 2253 to 3277; HXB2). All clusters and the recombinant clade correspond to sequences from the RCC in Masaka District. The numbers at the nodes indicate the MRCA and the purple rectangles indicate the 95 % highest posterior density. The numbers at the tips represent the sampling time for each sequence, and the colour of the squares denotes the patient’s sex (blue, male; red, female). The horizontal axis is expressed in calendar years.

Fig. 2.. Bayesian Skyride plot showing the changes in the estimated viral effective population size for subtypes A1 and D in Uganda across time. The horizontal axis is expressed in calendar years.

Fig. 3.. Inferred routes of HIV subtypes A1 (in blue) and D (in green) spread between the four Ugandan locations considered, highlighted with red rectangles. Only the statistically significant routes (supported by BF >3) are shown. The dates accompanying each arrow indicate approximately when these movements occurred in time. This figure was constructed using maps from MapBox (www.mapbox.com).