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Re-evaluating evolution in the HIV reservoir

Nature volume 551, pages E6–E9 (2017)Cite this article

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ARISING FROM R. Lorenzo-Redondo et al. Nature 530, 51–56 (2016); doi:10.1038/nature16933

Despite antiretroviral therapy (ART), a latent reservoir of replication-competent HIV-1 persists in resting memory CD4+ T cells and precludes a cure1,2,3,4,5,6. Lorenzo-Redondo et al.7 analysed HIV-1 sequences collected from three individuals during the first six months of ART, discovered specific patterns of sequence evolution, and concluded that viral replication persists during therapy. We believe that these evolutionary patterns are artefacts of rapidly decaying viral subpopulations present during the first months of therapy and are not characteristic of the long-lived reservoir. We therefore argue that ref. 7 does not provide evidence that ongoing replication is an additional barrier to a cure for treated individuals who consistently maintain low viral loads. There is a Reply to this Comment by Lorenzo-Redondo, R. et al. Nature 551, 10.1038/nature24635 (2017).

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Figure 1: For the first six months of ART, the persistent latent reservoir makes up a minority of sampled sequences.
Figure 2: Simulated decay of labile infected cell population creates misleading appearance of viral replication and evolution in first six months of treatment.

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Authors and Affiliations

  1. Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, USA

    Daniel I. S. Rosenbloom

  2. Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, USA

    Alison L. Hill

  3. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Sarah B. Laskey & Robert F. Siliciano

  4. Howard Hughes Medical Institute, Baltimore, Maryland, USA

    Robert F. Siliciano

Authors
  1. Daniel I. S. Rosenbloom
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  2. Alison L. Hill
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  3. Sarah B. Laskey
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  4. Robert F. Siliciano
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Contributions

Wrote the manuscript: D.I.S.R., A.L.H., S.B.L., R.F.S. Simulations and phylogenetic analyses: D.I.S.R., A.L.H., R.F.S. Estimation of labile compartments: S.B.L., R.F.S.

Corresponding author

Correspondence to Robert F. Siliciano.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Table 1 Analysis of post-treatment simulated samples based on sequences obtained before treatment14
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This file contains Supplementary Methods and Supplementary References. (PDF 428 kb)

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Supplementary Data

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Rosenbloom, D., Hill, A., Laskey, S. et al. Re-evaluating evolution in the HIV reservoir. Nature 551, E6–E9 (2017). https://doi.org/10.1038/nature24634

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