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<p>Antiretroviral therapy (ART) interruption typically leads to rapid HIV-1 viral rebound in people with HIV-1. To develop an HIV-1 cure, insight into immunological mechanisms capable of preventing HIV-1 viral rebound is urgently needed. Here, we describe three exceptional post-intervention controllers (PICs) who maintained ART-free virological control for &gt;6.5 years (ongoing), &gt;7.5 years (ongoing) and 2.5 years following administration of broadly neutralizing antibodies. PICs had quantifiable genetically intact/inducible infectious proviral reservoirs that were increasingly clonal and located in nongenic/centromeric chromosomal regions, indicating immune-mediated selection. Potent autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. In one PIC, viral rebound following 2.5 years of ART-free control was associated with accumulated viral mutations that resulted in escape from neutralizing antibody and T cell responses. Collectively, our findings support developing HIV-1 curative strategies aimed at enhancing pre-existing adaptive immune responses.</p>

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Autologous neutralizing antibodies and polyfunctional T cells contribute to long-term HIV-1 post-intervention control

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月3日

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  • Katie Fisher,
  • Mauro A. Garcia,
  • Giacomo S. Frattari,
  • Chloé Naasz,
  • Junlin Zhuo,
  • Miriam Rosás-Umbert,
  • Lisa L. Dietz,
  • Anna Karina Juhl,
  • Emma Falling Iversen,
  • Rikke Olesen,
  • Mariane H. Schleimann,
  • Marie H. Pahus,
  • Isik S. Johansen,
  • Merle Henderson,
  • Leah Carrere,
  • Isabelle Roseto,
  • Ce Gao,
  • Xu G. Yu,
  • Emily J. Fray,
  • Beril Aydin,
  • Donald Lubbeck,
  • Jun Lai,
  • Francesco R. Simonetti,
  • Ali Danesh,
  • Itzayana Miller,
  • Pilar Mendoza,
  • Julia Niessl,
  • Christian Gaebler,
  • Michael S. Seaman,
  • Daniel E. Kaufmann,
  • Clara Lehmann,
  • Henning Gruell,
  • Florian Klein,
  • Marina Caskey,
  • Michel C. Nussenzweig,
  • Martin Tolstrup,
  • R. Brad Jones,
  • Jesper D. Gunst,
  • Janet D. Siliciano,
  • Mathias Lichterfeld,
  • Robert F. Siliciano,
  • Ole S. Søgaard

摘要

Antiretroviral therapy (ART) interruption typically leads to rapid HIV-1 viral rebound in people with HIV-1. To develop an HIV-1 cure, insight into immunological mechanisms capable of preventing HIV-1 viral rebound is urgently needed. Here, we describe three exceptional post-intervention controllers (PICs) who maintained ART-free virological control for >6.5 years (ongoing), >7.5 years (ongoing) and 2.5 years following administration of broadly neutralizing antibodies. PICs had quantifiable genetically intact/inducible infectious proviral reservoirs that were increasingly clonal and located in nongenic/centromeric chromosomal regions, indicating immune-mediated selection. Potent autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4+ and CD8+ T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. In one PIC, viral rebound following 2.5 years of ART-free control was associated with accumulated viral mutations that resulted in escape from neutralizing antibody and T cell responses. Collectively, our findings support developing HIV-1 curative strategies aimed at enhancing pre-existing adaptive immune responses.