PMID- 36877848 OWN - NLM STAT- MEDLINE DCOM- 20230308 LR - 20230923 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 120 IP - 11 DP - 2023 Mar 14 TI - HIV post-treatment controllers have distinct immunological and virological features. PG - e2218960120 LID - 10.1073/pnas.2218960120 [doi] LID - e2218960120 AB - 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 /=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. FAU - Etemad, Behzad AU - Etemad B AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139. FAU - Sun, Xiaoming AU - Sun X AUID- ORCID: 0000-0001-6266-6869 AD - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139. FAU - Li, Yijia AU - Li Y AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139. FAU - Melberg, Meghan AU - Melberg M AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139. FAU - Moisi, Daniela AU - Moisi D AUID- ORCID: 0000-0003-2326-7683 AD - School of Medicine, Case Western Reserve University, Cleveland, OH 44106. FAU - Gottlieb, Rachel AU - Gottlieb R AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139. FAU - Ahmed, Hayat AU - Ahmed H AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139. FAU - Aga, Evgenia AU - Aga E AD - Harvard T. H. Chan School of Public Health, Boston, MA 02115. FAU - Bosch, Ronald J AU - Bosch RJ AD - Harvard T. H. Chan School of Public Health, Boston, MA 02115. FAU - Acosta, Edward P AU - Acosta EP AD - School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233. FAU - Yuki, Yuko AU - Yuki Y AUID- ORCID: 0000-0003-1721-6003 AD - Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702. AD - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814. FAU - Martin, Maureen P AU - Martin MP AUID- ORCID: 0000-0002-0990-3500 AD - Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702. AD - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814. FAU - Carrington, Mary AU - Carrington M AUID- ORCID: 0000-0002-2692-2180 AD - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139. AD - Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702. AD - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814. FAU - Gandhi, Rajesh T AU - Gandhi RT AD - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114. FAU - Jacobson, Jeffrey M AU - Jacobson JM AD - School of Medicine, Case Western Reserve University, Cleveland, OH 44106. FAU - Volberding, Paul AU - Volberding P AD - School of Medicine, University of California San Francisco, San Francisco, CA 94143. FAU - Connick, Elizabeth AU - Connick E AUID- ORCID: 0000-0002-0465-6248 AD - Department of Medicine, University of Arizona, Tucson, AZ 85724. FAU - Mitsuyasu, Ronald AU - Mitsuyasu R AUID- ORCID: 0000-0002-2627-6246 AD - School of Medicine, University of California Los Angeles, Los Angeles, CA 90095. FAU - Frank, Ian AU - Frank I AD - School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. FAU - Saag, Michael AU - Saag M AUID- ORCID: 0000-0002-8866-1043 AD - School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233. FAU - Eron, Joseph J AU - Eron JJ AUID- ORCID: 0000-0002-4938-0644 AD - Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. FAU - Skiest, Daniel AU - Skiest D AD - Department of Medicine, University of Massachusetts Chan Medical School - Baystate, Springfield, MA 01199. FAU - Margolis, David M AU - Margolis DM AUID- ORCID: 0000-0001-5714-0002 AD - Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. FAU - Havlir, Diane AU - Havlir D AD - School of Medicine, University of California San Francisco, San Francisco, CA 94143. FAU - Schooley, Robert T AU - Schooley RT AD - Department of Medicine, University of California San Diego, San Diego, CA 92103. FAU - Lederman, Michael M AU - Lederman MM AUID- ORCID: 0000-0001-9247-8025 AD - School of Medicine, Case Western Reserve University, Cleveland, OH 44106. FAU - Yu, Xu G AU - Yu XG AD - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139. FAU - Li, Jonathan Z AU - Li JZ AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139. LA - eng GR - UM1 AI069501/AI/NIAID NIH HHS/United States GR - U01 AI069412/AI/NIAID NIH HHS/United States GR - UM1 AI069534/AI/NIAID NIH HHS/United States GR - UM1 AI164560/AI/NIAID NIH HHS/United States GR - U01 AI068636/AI/NIAID NIH HHS/United States GR - HHSN261200800001C/RC/CCR NIH HHS/United States GR - P30 AI060354/AI/NIAID NIH HHS/United States GR - HHSN261200800001E/CA/NCI NIH HHS/United States GR - T32 AI007387/AI/NIAID NIH HHS/United States GR - UM1 AI069423/AI/NIAID NIH HHS/United States GR - P30 AI045008/AI/NIAID NIH HHS/United States GR - UM1 AI069412/AI/NIAID NIH HHS/United States GR - UM1 AI068634/AI/NIAID NIH HHS/United States GR - R01 AI150396/AI/NIAID NIH HHS/United States GR - UM1 AI106701/AI/NIAID NIH HHS/United States GR - U01 AI068634/AI/NIAID NIH HHS/United States GR - UM1 AI068636/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230306 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 63231-63-0 (RNA) SB - IM MH - Humans MH - *CD8-Positive T-Lymphocytes MH - Killer Cells, Natural MH - Lymphocyte Activation MH - RNA MH - *HIV Infections/drug therapy/immunology MH - Viremia PMC - PMC10089217 OTO - NOTNLM OT - HIV OT - T cell OT - analytical treatment interruption OT - post-treatment controller OT - reservoir COIS- J.Z.L has received research support from Merck. M.M.L. and X.G.Y have received research support from Gilead Sciences. I.F. has received honoraria as a consultant to Gilead Sciences, ViiV Healthcare, and Merck and has received research support from Janssen Therapeutics, Sanofi, Moderna, and Pfizer. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. EDAT- 2023/03/07 06:00 MHDA- 2023/03/09 06:00 PMCR- 2023/09/06 CRDT- 2023/03/06 15:23 PHST- 2023/03/06 15:23 [entrez] PHST- 2023/03/07 06:00 [pubmed] PHST- 2023/03/09 06:00 [medline] PHST- 2023/09/06 00:00 [pmc-release] AID - 202218960 [pii] AID - 10.1073/pnas.2218960120 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2218960120. doi: 10.1073/pnas.2218960120. Epub 2023 Mar 6.