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

Journal name:
Nature Medicine
Volume:
21,
Pages:
1139–1141
Year published:
DOI:
doi:10.1038/nm.3932
Received
Accepted
Published online

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.

At a glance

Figures

  1. The positive relationship between HIV-1 diversity and viral loads over the first year after HIV-1 diagnosis.
    Figure 1: The positive relationship between HIV-1 diversity and viral loads over the first year after HIV-1 diagnosis.

    HIV-1 diversity was measured at the time of HIV-1 diagnosis. Individual log VL values, predicted means and 95% confidence intervals are shown at each post-infection visit. (a,b) Step (a) and RV144 (b) trial participants with homogeneous or heterogeneous viral populations. (c,d) Low, medium and high levels of env diversity in Step (c) and RV144 (d) trial participants. Models were adjusted for baseline subject characteristics and assumed that the effects of heterogeneity and diversity are constant over time.

  2. The negative relationship between HIV-1 diversity and CD4+ T cell counts 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.

    HIV-1 diversity was measured at the time of HIV-1 diagnosis. Individual CD4+ T cell count measurements and predicted means and 95% confidence intervals are shown at each post-infection visit. (a,b) Step (a) and RV144 (b) trial participants with homogeneous or heterogeneous viral populations. (c,d) Low, medium and high levels of env diversity in Step (c) and RV144 (d) trial participants. Models were adjusted for baseline subject characteristics and assumed that the effects of heterogeneity and diversity are constant over time.

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Author information

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

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.

Competing financial 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.

Corresponding author

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Supplementary information

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    Supplementary Note and Supplementary Figure 1

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