Autologous neutralizing antibodies and polyfunctional T cells contribute to long-term HIV-1 post-intervention control
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<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.
Authors
- Merle Henderson (ORCID: https://orcid.org/0000-0003-3326-9674)
- Henning Gruell (ORCID: https://orcid.org/0000-0002-0725-7138)
- Janet D. Siliciano (ORCID: https://orcid.org/0000-0001-6712-3775)
- S. Schieber
- Giacomo S. Frattari (ORCID: https://orcid.org/0000-0001-7765-6428)
- Julia Niessl (ORCID: https://orcid.org/0000-0001-8852-1924)
- J. Lai
- Pilar Mendoza (ORCID: https://orcid.org/0000-0003-2957-1811)
- Katie Fisher (ORCID: https://orcid.org/0000-0002-8732-706X)
- Francesco R. Simonetti (ORCID: https://orcid.org/0000-0002-4165-660X)
- Míriam Rosás-Umbert (ORCID: https://orcid.org/0000-0002-2850-6586)
- Mauro Garcia (ORCID: https://orcid.org/0000-0002-8520-7144)
- Emily J. Fray (ORCID: https://orcid.org/0000-0002-5850-6237)
- Ole S. Søgaard (ORCID: https://orcid.org/0000-0001-9107-2023)
- Emma Falling Iversen (ORCID: https://orcid.org/0000-0003-2770-1942)
- Jesper Damsgaard Gunst (ORCID: https://orcid.org/0000-0002-3787-0259)
- Marie H. Pahus (ORCID: https://orcid.org/0000-0003-0776-3847)
- Junlin Zhuo (ORCID: https://orcid.org/0000-0002-5311-6707)
- Christian Gaebler (ORCID: https://orcid.org/0000-0001-7295-8128)
- Anna Karina Juhl (ORCID: https://orcid.org/0000-0001-6079-5173)
- Xiaojuan Yu (ORCID: https://orcid.org/0000-0003-4600-7841)
- Beril Aydin
- Leah Carrere (ORCID: https://orcid.org/0009-0000-2481-5501)
- Chloé M. Naasz
- Florian Klein (ORCID: https://orcid.org/0000-0002-7082-0317)
- Marina F. Caskey
- Ce Gao
- Michel C. Nussenzweig
- Ali Danesh
- Isik S. Johansen
- Mathias Lichterfeld
- Donald Lubbeck
- Lisa L. Dietz
- Daniel E. Kaufmann
- Rikke Olesen
- Isabelle Roseto
- Robert F. Siliciano
- R. Brad Jones
Institutions
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Johns Hopkins University (US)
- University of Cologne (DE)
- Aarhus University (DK)
- Cornell University (US)
- Johns Hopkins Medicine (US)
- Odense University Hospital (DK)
- Aarhus University Hospital (DK)
- Ragon Institute of MGH, MIT and Harvard (US)
- Humboldt-Universität zu Berlin (DE)
- NIHR Imperial Biomedical Research Centre (GB)
- German Center for Infection Research (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Centre Hospitalier de l’Université de Montréal (CA)
- University Hospital Cologne (DE)
- Weill Cornell Medicine (US)
- Imperial College London (GB)
- Université de Montréal (CA)
- Rockefeller University (US)
- University of Lausanne (CH)
Publication Details
- Journal
- Nature Immunology
- Published
- 2026-03-03
- DOI
- https://doi.org/10.1038/s41590-026-02448-z
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00