@article{c2dfbcca010b4da6930b24a60cf8874c,
title = "HIV post-treatment controllers have distinct immunological and virological features",
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.",
keywords = "HIV, T cell, analytical treatment interruption, post-treatment controller, reservoir",
author = "Behzad Etemad and Xiaoming Sun and Yijia Li and Meghan Melberg and Daniela Moisi and Rachel Gottlieb and Hayat Ahmed and Evgenia Aga and Bosch, {Ronald J.} and Acosta, {Edward P.} and Yuko Yuki and Martin, {Maureen P.} and Mary Carrington and Gandhi, {Rajesh T.} and Jacobson, {Jeffrey M.} and Paul Volberding and Elizabeth Connick and Ronald Mitsuyasu and Ian Frank and Michael Saag and Eron, {Joseph J.} and Daniel Skiest and Margolis, {David M.} and Diane Havlir and Schooley, {Robert T.} and Lederman, {Michael M.} and Yu, {Xu G.} and Li, {Jonathan Z.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank the participants, staff, and investigators of the ACTG studies A371 (Paul Volberding and Elizabeth Connick), A5024 (J. Michael Kilby and R.M.), A5068 (J.M.J., I.F., M.S., and J.J.E.), A5170 (D.S., D.M.M., and D.H.), and A5197 (R.T.S., M.M.L., and D.H.). We appreciate Michael Bale{\textquoteright}s help with the panmixia testing, Laura Gray{\textquoteright}s assistance with single genome sequencing (SGS), and the help of Nicole Stange-Thomann and the Massachusetts General Hospital Center for Computational and Integrative Biology DNA Core. This study was funded in part by the American Foundation for AIDS Research and NIH grants AI068634, AI068636, AI106701, AI150396, AI164560, P30 AI045008, UM1 AI069534, and AI069412. Y.L. was funded by NIH T32 training grant (5T32AI007387-32, PI Kuritzkes, Daniel). R.T.G. and J.Z.L. received grant funding from the Harvard University Center for AIDS Research (NIH P30 AI060354). This project has also been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. Publisher Copyright: Copyright {\textcopyright} 2023 the Author(s).",
year = "2023",
month = mar,
day = "10",
doi = "10.1073/pnas.2218960120",
language = "English (US)",
volume = "120",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "11",
}