Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac<sub>239</sub>-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8<sup>+</sup> T cells in lymph nodes and reduced expression of BCL-2 in CD4<sup>+</sup> T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.
Authors
- Jacob D. Estes (ORCID: https://orcid.org/0000-0002-9652-6394)
- Guido Silvestri (ORCID: https://orcid.org/0000-0001-6602-2470)
- Chelsea Wallace
- Susan Pereira Ribeiro (ORCID: https://orcid.org/0000-0002-3127-3138)
- Perla M. Del Río Estrada (ORCID: https://orcid.org/0000-0003-3366-3268)
- Gabriela Pacheco Sánchez (ORCID: https://orcid.org/0000-0002-0394-0589)
- Sherrie Jean (ORCID: https://orcid.org/0000-0001-8028-8160)
- Timothy N. Hoang (ORCID: https://orcid.org/0000-0002-7781-1130)
- Kevin Nguyen (ORCID: https://orcid.org/0000-0002-4348-1110)
- Ruy M. Ribeiro (ORCID: https://orcid.org/0000-0002-3988-8241)
- Rafick‐Pierre Sékaly (ORCID: https://orcid.org/0000-0002-7816-4828)
- Jeffrey D. Lifson (ORCID: https://orcid.org/0000-0002-9494-0268)
- G. Raghunathan
- Luca Micci (ORCID: https://orcid.org/0000-0003-1980-4271)
- Mirko Paiardini (ORCID: https://orcid.org/0000-0002-7276-3600)
- Bonnie J. Howell (ORCID: https://orcid.org/0000-0002-5915-9943)
- Khader Ghneim (ORCID: https://orcid.org/0000-0003-0548-1942)
- Eric Rimmer
- Hugo Soudeyns (ORCID: https://orcid.org/0000-0001-5857-3176)
- Justin Harper (ORCID: https://orcid.org/0000-0002-6948-3501)
- Robert Balderas (ORCID: https://orcid.org/0000-0002-8734-8629)
- Giuliana Xavier de Medeiros (ORCID: https://orcid.org/0000-0003-0464-3188)
- Chi Ngai Chan (ORCID: https://orcid.org/0000-0001-9106-9481)
- Zachary Strongin
- Felipe ten-Caten (ORCID: https://orcid.org/0000-0001-7771-1490)
- Daria J. Hazuda (ORCID: https://orcid.org/0000-0002-6894-1056)
- Guoxin Wu (ORCID: https://orcid.org/0009-0008-8449-8155)
- Cinthia Pastuskova
- Adam‐Nicolas Pelletier
- Daniel M. Gorman
Institutions
- Oregon National Primate Research Center (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Emory Healthcare (US)
- Los Alamos National Laboratory (US)
- Becton Dickinson (United States) (US)
- Emory University (US)
- Oregon Health & Science University (US)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Quantitative BioSciences (US)
- Instituto Nacional de Enfermedades Respiratorias (MX)
- Frederick National Laboratory for Cancer Research (US)
- Children's Cancer Therapy Development Institute (US)
- Biolog (United States) (US)
- Atlanta VA Medical Center (US)
- Université de Montréal (CA)
Publication Details
- Journal
- Nature Immunology
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1038/s41590-024-01952-4
- Citations
- 20
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 5.87
Funders
- U.S. Department of Health and Human Services
- Gilead Sciences
- Emory University
- National Institutes of Health
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases