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HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders

Nature Medicine volume 21, pages 1139–1141 (2015)Cite this article

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Abstract

Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically linked HIV-1 founder variants represent a minority of HIV-1 infections, we found—in two different cohorts—that more diverse HIV-1 populations in early infection were associated with significantly higher VL 1 year after HIV-1 diagnosis.

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Figure 1: The positive relationship between HIV-1 diversity and viral loads over the first year after HIV-1 diagnosis.
Figure 2: The negative relationship between HIV-1 diversity and CD4+ T cell counts over the first year after HIV-1 diagnosis.

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Acknowledgements

We would like to thank the participants in the Step study and the RV144 trial for their contributions to this research and Lisa Reilly for editorial help. Sequencing and analysis were performed under grants from the National Institute of Allergy and Infectious Diseases: US Public Health Service grant AI41505; Interagency Agreement Y1-AI-2642-12 with the US Army Medical Research and Material Command; US National Institutes of Health (NIH) grant 2R37AI05465-10 to P.B.G. This work was also supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the US Department of Defense. The opinions expressed herein are those of the authors and should not be construed as official or representing the views of the US Department of Defense or the Department of the Army. This does not alter our adherence to policies on sharing data and materials.

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Authors and Affiliations

  1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Holly Janes, Nicole Frahm, Ann Duerr, John Hural, Lawrence Corey, Steve G Self, Susan P Buchbinder, M Juliana McElrath & Peter B Gilbert

  2. Department of Global Health, University of Washington, Seattle, Washington, USA

    Joshua T Herbeck, Nicole Frahm & M Juliana McElrath

  3. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

    Sodsai Tovanabutra, Rasmi Thomas, Robert M Paris, Merlin L Robb, Nelson L Michael, Jerome H Kim & Morgane Rolland

  4. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA

    Sodsai Tovanabutra, Rasmi Thomas, Merlin L Robb & Morgane Rolland

  5. Department of Medicine, University of Washington, Seattle, Washington, USA

    M Juliana McElrath

  6. Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA

    M Juliana McElrath

  7. Royal Thai Army Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

    Robert J O'Connell & Sorachai Nitayaphan

  8. Thai Ministry of Public Health, Nonthaburi, Thailand

    Supachai Rerks-Ngarm

  9. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    Punnee Pitisuttihum & Jaranit Kaewkungwal

  10. Department of Microbiology, University of Washington, Seattle, Washington, USA

    James I Mullins

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  1. Holly Janes
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Contributions

H.J. and M.R. designed and performed experiments, analyzed data and wrote the manuscript. S.T., A.D., J.T.H., L.C., S.G.S., S.P.B., M.J.M., R.J.O'C., R.M.P., S.R.-N., S.N., P.P., J.K., M.L.R., N.L.M., J.H.K. and P.B.G. oversaw the vaccine trials and clinical aspects. J.T.H., R.T., N.F., M.J.M., M.L.R., N.L.M., J.I.M., J.H.K. and P.B.G. edited the manuscript.

Corresponding author

Correspondence to Morgane Rolland.

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Competing interests

M.R., S.T., R.T. and M.L.R. are employees of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

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Supplementary Note and Supplementary Figure 1 (PDF 1044 kb)

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Janes, H., Herbeck, J., Tovanabutra, S. et al. HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders. Nat Med 21, 1139–1141 (2015). https://doi.org/10.1038/nm.3932

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