A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption

Viviane M. Andrade, Carla Mavian, Dunja Babic, Thaissa Cordeiro, Mark Sharkey, Labelle Barrios, Christian Brander, Javier Martinez-Picado, Judith Dalmau, Anuska Llano, Jonathan Z. Li, Jeffrey Jacobson, Christy L. Lavine, Michael S. Seaman, Marco Salemi, Mario Stevenson

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

HIV-1 persists in cellular reservoirs that can reignite viremia if antiretroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses constructed with individual envelope genes that were obtained from plasma of six individuals undergoing analytic treatment interruption (ATI). M-tropic viruses could also be enriched from post-ATI plasma using macrophagespecific (CD14) but not CD4+ T cell-specific (CD3) antibodies, suggesting that M-tropic viruses had a macrophage origin. Molecular clock analysis indicated that the establishment of M-tropic HIV-1 variants predated ATI. Collectively, these data suggest that macrophages are a viral reservoir in HIV-1-infected individuals on effective ART and that M-tropic variants can appear in rebounding viremia when treatment is interrupted. These findings have implications for the design of curative strategies for HIV-1.

Original languageEnglish (US)
Pages (from-to)9981-9990
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number18
DOIs
StatePublished - May 5 2020

Keywords

  • Analytical treatment interruption
  • HIV-1 reservoirs
  • Macrophages

ASJC Scopus subject areas

  • General

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    Andrade, V. M., Mavian, C., Babic, D., Cordeiro, T., Sharkey, M., Barrios, L., Brander, C., Martinez-Picado, J., Dalmau, J., Llano, A., Li, J. Z., Jacobson, J., Lavine, C. L., Seaman, M. S., Salemi, M., & Stevenson, M. (2020). A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption. Proceedings of the National Academy of Sciences of the United States of America, 117(18), 9981-9990. https://doi.org/10.1073/pnas.1917034117