Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations.

The processes that permitted a few SIV strains to emerge epidemically as HIV groups remain elusive. Paradigmatic theories propose factors that may have facilitated adaptation to the human host (e.g., unsafe injections), none of which provide a coherent explanation for the timing, geographical origin, and scarcity of epidemic HIV strains. Our updated molecular clock analyses established relatively narrow time intervals (roughly 1880–1940) for major SIV transfers to humans. Factors that could favor HIV emergence in this time frame may have been genital ulcer disease (GUD), resulting in high HIV-1 transmissibility (4–43%), largely exceeding parenteral transmissibility; lack of male circumcision increasing male HIV infection risk; and gender-skewed city growth increasing sexual promiscuity. We surveyed colonial medical literature reporting incidences of GUD for the relevant regions, concentrating on cities, suffering less reporting biases than rural areas. Coinciding in time with the origin of the major HIV groups, colonial cities showed intense GUD outbreaks with incidences 1.5–2.5 orders of magnitude higher than in mid 20th century. We surveyed ethnographic literature, and concluded that male circumcision frequencies were lower in early 20th century than nowadays, with low rates correlating spatially with the emergence of HIV groups. We developed computer simulations to model the early spread of HIV-1 group M in Kinshasa before, during and after the estimated origin of the virus, using parameters derived from the colonial literature. These confirmed that the early 20th century was particularly permissive for the emergence of HIV by heterosexual transmission. The strongest potential facilitating factor was high GUD levels. Remarkably, the direct effects of city population size and circumcision frequency seemed relatively small. Our results suggest that intense GUD in promiscuous urban communities was the main factor driving HIV emergence. Low circumcision rates may have played a role, probably by their indirect effects on GUD.