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HIV post-treatment controllers have distinct immunological and virological features

  1. Author:
    Etemad, Behzad
    Sun, Xiaoming [ORCID]
    Li, Yijia
    Melberg, Meghan
    Moisi, Daniela [ORCID]
    Gottlieb, Rachel
    Ahmed, Hayat
    Aga, Evgenia
    Bosch, Ronald J
    Acosta, Edward P
    Yuki,Yuko [ORCID]
    Martin, Maureen P [ORCID]
    Carrington,Mary [ORCID]
    Gandhi, Rajesh T
    Jacobson, Jeffrey M
    Volberding, Paul
    Connick, Elizabeth [ORCID]
    Mitsuyasu, Ronald [ORCID]
    Frank, Ian
    Saag, Michael [ORCID]
    Eron, Joseph J [ORCID]
    Skiest, Daniel
    Margolis, David M [ORCID]
    Havlir, Diane
    Schooley, Robert T
    Lederman, Michael M [ORCID]
    Yu, Xu G
    Li, Jonathan Z

  2. Author Address

    Department of Medicine, Brigham and Women 39;s Hospital, Harvard Medical School, Boston, MA 02139., Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139., School of Medicine, Case Western Reserve University, Cleveland, OH 44106., Harvard T. H. Chan School of Public Health, Boston, MA 02115., School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233., Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702., Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814., Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., School of Medicine, University of California San Francisco, San Francisco, CA 94143., Department of Medicine, University of Arizona, Tucson, AZ 85724., School of Medicine, University of California Los Angeles, Los Angeles, CA 90095., School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Department of Medicine, University of Massachusetts Chan Medical School - Baystate, Springfield, MA 01199., Department of Medicine, University of California San Diego, San Diego, CA 92103.,
    1. Year: 2023
    2. Date: Mar 14
    3. Epub Date: 2023 03 06
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 120
    2. 11
    3. Pages: e2218960120
  4. Type of Article: Article
  5. Article Number: e2218960120
  1. Abstract:

    HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads =400 copies/mL for =24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4+ and CD8+ T cell activation, lower CD4+ T cell exhaustion, and more robust Gag-specific CD4+ T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4+ T cell% and CD4+/CD8+ ratio, more functional NK cells, and a lower CD4+ T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.

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External Sources

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  2. DOI: 10.1073/pnas.2218960120
  3. PMID: 36877848

Library Notes

  1. Fiscal Year: FY2022-2023
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