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1970s and ‘Patient 0’ HIV-1 genomes illuminate early HIV/AIDS history in North America

Nature volume 539, pages 98101 (03 November 2016) | Download Citation

This article has been updated


The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s1,2 and an even older presence in the Caribbean2. However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious3,4 and the earliest movements of the virus within the US are unknown. We serologically screened >2,000 1970s serum samples and developed a highly sensitive approach for recovering viral RNA from degraded archival samples. Here, we report eight coding-complete genomes from US serum samples from 1978–1979—eight of the nine oldest HIV-1 group M genomes to date. This early, full-genome ‘snapshot’ reveals that the US HIV-1 epidemic exhibited extensive genetic diversity in the 1970s but also provides strong evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian phylogenetic analyses estimate the jump to the US at around 1970 and place the ancestral US virus in New York City with 0.99 posterior probability support, strongly suggesting this was the crucial hub of early US HIV/AIDS diversification. Logistic growth coalescent models reveal epidemic doubling times of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid early expansion in each location3. Comparisons with more recent data reveal many of these insights to be unattainable without archival, full-genome sequences. We also recovered the HIV-1 genome from the individual known as ‘Patient 0’ (ref. 5) and found neither biological nor historical evidence that he was the primary case in the US or for subtype B as a whole. We discuss the genesis and persistence of this belief in the light of these evolutionary insights.

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  • 02 October 2016

    In the online version of this paper the images in Figures 2 and 3 were switched, this has been corrected.


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We thank C. Stevens and D. Hemmerlein for facilitating access to archival sera; G.-Z. Han, A. Bjork, W. Switzer, V. Sullivan, R. Ruboyianes and P. Sprinkle for technical assistance; T. Spira and M. Owen for geographical data on some published sequences; and the NIH AIDS Reagent program for providing reference virus samples US657 and HT599. W. W. Darrow led the initial 1982 cluster investigation and provided R.A.M. with access to his copies of archival CDC documents. This work was supported by NIH/NIAID R01AI084691 and the David and Lucile Packard Foundation (M.W.); the Wellcome Trust (080651), the University of Oxford’s Clarendon Fund, the Economic and Social Research Council (PTA-026-27-2838), and a J. Armand Bombardier Internationalist Fellowship (R.A.M.); the Research Fund KU Leuven (Onderzoeksfonds KU Leuven, Program Financing no. PF/10/018) and the ‘Fonds voor Wetenschappelijk Onderzoek Vlaanderen’ (FWO) (G066215N) (P.L); and NSF DMS 1264153, NIH R01 HG006139 and NIH R01 AI107034 (M.A.S.).

Author information


  1. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona 85721, USA

    • Michael Worobey
    •  & Thomas D. Watts
  2. Department of History and Philosophy of Science, University of Cambridge, Cambridge CB2 3RH, UK

    • Richard A. McKay
  3. Departments of Biomathematics, Biostatistics and Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA

    • Marc A. Suchard
  4. Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA

    • Timothy Granade
    • , Walid Heneine
    •  & Harold W. Jaffe
  5. UCB, Brussels BE-1070, Belgium

    • Dirk E. Teuwen
  6. Laboratory of Infectious Disease Prevention, The New York Blood Center, New York, New York 10065, USA

    • Beryl A. Koblin
  7. Department of Microbiology and Immunology, Rega Institute, KU Leuven—University of Leuven, Minderbroedersstaat 10, 3000 Leuven, Belgium

    • Philippe Lemey


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M.W., H.W.J., P.L. and R.A.M. conceived the study. T.D.W and M.W. designed the RNA jackhammering method. T.D.W. generated the sequences. B.A.K. provided serum samples from New York City. W.H. and T.G. acquired specimens and provided serological data. D.E.T. provided conceptual input. M.W., M.A.S. and P.L. prepared the data sets and performed the phylogenetic analyses. R.A.M. performed the historical analyses. M.W., H.W.J., P.L. and R.A.M. wrote the paper. All authors discussed the results and commented on the manuscript. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Competing interests

A patent, ‘Methods and systems for RNA or DNA detection and sequencing’ (US patent application 62/325,320), has been filed with the United States Patent and Trademark Office. It will be used to facilitate the licensing of this methodology.

Corresponding authors

Correspondence to Michael Worobey or Richard A. McKay.

Reviewer Information Nature thanks K. Andersen and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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