The precise origins of the western hemispheric HIV/AIDS pandemic remain contentious. Phylogenetic studies based upon HIV-1 sequences sampled after (in most cases long after) the recognition of AIDS in 1981 have suggested a lengthy cryptic period of circulation in the U.S. and Canada throughout the 1970s, and an even older presence in the Caribbean. However, no comprehensive evolutionary genomic analysis of HIV-1 in North America closer to the putative emergence of the virus in the 1970s has been possible since no non-African HIV-1 complete genomes from that era have been sequenced to date.

Here, we combine approaches from molecular biology, phylogenetics, and historical analysis to investigate the timing and geography of the emergence of HIV-1 group M subtype B in the U.S. We designed an approach to overcome the challenge of recovering HIV-1 genetic material from older serum specimens in which viral RNA template material is highly fragmented and at low concentration. We recovered near-full length HIV-1 genome sequences from eight U.S. patient serum samples from 1978-79 (comprising eight of the nine earliest HIV-1 group M genomes sequenced worldwide to date) and also from the individual known as ‘Patient 0’. We then used maximum likelihood and Bayesian ‘relaxed molecular clock’ phylogenetic and phylogenomic methods to infer timing and geography.

This early genomic ‘snapshot’ of HIV-1 reveals that by 1978-79 the HIV-1 epidemic in the U.S. already exhibited extensive genetic diversity – particularly in New York City (NYC) – having emerged around 1970 from a founder virus drawn from an older and more diverse subtype B epidemic in the Caribbean. Moreover, there is neither biological nor historical evidence that Patient 0 was the primary case in the U.S. or for subtype B as a whole.

Our findings reveal a series of key founder events in the genesis of the subtype B epidemic, with a single virus moving from the African epicenter of HIV-1 group M to the Caribbean by 1967 [1964-1970], a single virus moving from the Caribbean to establish an epidemic in NYC by 1971 [1969-73], and yet another single virus moving from there to San Francisco by ~1975 (but with extensive geographical mixing in the U.S. and beyond shortly thereafter). We discuss, in the context of these insights into the early spread of HIV/AIDS in North America, the genesis and persistence of beliefs about ‘Patient 0’ that are unsupported by scientific data.