Env-specific antibodies promote post-treatment control in SIV-infected macaques
Abstract Viral latency reversal was observed in simian immunodeficiency virus (SIV)-infected rhesus macaques receiving antiretroviral therapy (ART), CD8α lymphocyte depletion and N-803 immunotherapy. However, this therapeutic approach did not reduce the viral reservoir size and treatment interruption resulted in rapid virus rebound. Here, to address this shortfall, we used four anti-SIV Env-specific rhesus IgG1 monoclonal antibodies (RhmAbs) that recognize unique targets on the SIV envelope. SIV mac239 -infected macaques were treated with ART only (group 1); ART + RhmAbs (group 2); or ART + RhmAbs + CD8α-depletion + N-803 (group 3). Robust latency reversal was only achieved in group 3. Viraemia rebounded in all macaques with similar kinetics after treatment interruption. However, compared with pre-ART viral loads, a greater fold reduction in rebound viraemia was seen in groups 2 and 3 and post-treatment control (PTC) required SIV RhmAbs. CD4 + T cells from macaques with PTC maintained low levels of intact SIV proviruses off ART and expressed increased interferon and decreased TGF-β signalling genes. This antiviral gene expression profile was also observed in CD4 + T cells with lower human immunodeficiency virus (HIV)-DNA content from ART-treated people with HIV. These results suggest that reduced virus production may contribute to PTC following ART interruption and provide a target for immune-based strategies to achieve durable viral control.
Authors
- Amir Dashti (ORCID: https://orcid.org/0000-0002-4679-7962)
- Vinh B. Dinh (ORCID: https://orcid.org/0000-0002-8148-8508)
- Rosemarie D. Mason (ORCID: https://orcid.org/0000-0001-7123-4902)
- Janet D'Angelo Siliciano (ORCID: https://orcid.org/0000-0001-6712-3775)
- Jeffrey T. Safrit (ORCID: https://orcid.org/0000-0001-7441-4423)
- Ashish Sharma (ORCID: https://orcid.org/0000-0001-9444-7046)
- Maud Mavigner (ORCID: https://orcid.org/0000-0001-9898-317X)
- Rafick‐Pierre Sékaly (ORCID: https://orcid.org/0000-0002-7816-4828)
- Emily J. Fray (ORCID: https://orcid.org/0000-0002-5850-6237)
- Jeffrey D. Lifson (ORCID: https://orcid.org/0000-0002-9494-0268)
- Deanna A. Kulpa (ORCID: https://orcid.org/0000-0002-0411-7295)
- Mirko Paiardini (ORCID: https://orcid.org/0000-0002-7276-3600)
- Anushka Singhal (ORCID: https://orcid.org/0009-0000-7001-3366)
- Guido Silvestri (ORCID: https://orcid.org/0000-0001-6602-2470)
- Ann Chahroudi (ORCID: https://orcid.org/0000-0001-7479-9546)
- Robert F. Siliciano (ORCID: https://orcid.org/0000-0002-1764-1993)
- Mario Roederer (ORCID: https://orcid.org/0000-0001-7448-7040)
- Jordan N. Goldy (ORCID: https://orcid.org/0000-0001-8803-8713)
- Nils Schoof (ORCID: https://orcid.org/0000-0003-0343-2776)
- Vidisha Singh (ORCID: https://orcid.org/0000-0002-8942-519X)
- Zain Siddiqi
- Divine Burgess
- Hannah King
Institutions
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Emory University (US)
- Johns Hopkins Medicine (US)
- Frederick National Laboratory for Cancer Research (US)
- National Institute of Allergy and Infectious Diseases (US)
- ImmunityBio (United States) (US)
- Children's Healthcare of Atlanta (US)
- Emory National Primate Research Center (US)
- Leidos Biomedical Research Inc. (United States) (US)
- Vaccine Research Center (US)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2026-11-10
- DOI
- https://doi.org/10.1038/s41564-026-02426-z
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00