Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques

Lim, So-Yon; Lee, Jina; Osuna, Christa E.; Vikhe, Pratik; Schalk, Dane R.; Chen, Elsa; Fray, Emily; Kumar, Mithra; Schultz-Darken, Nancy; Rakasz, Eva; Capuano, Saverio; Ladd, Ruby A.; Gil, Hwi Min; Evans, David T.; Jeng, Emily K.; Seaman, Michael; Martin, Malcolm; Van Dorp, Christiaan; Perelson, Alan S.; Wong, Hing C.; Siliciano, Janet D.; Siliciano, Robert; Safrit, Jeffrey T.; Nixon, Douglas F.; Soon-Shiong, Patrick; Nussenzweig, Michel; Whitney, James B.

doi:10.1126/science.adf7966

Title: Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques

Journal Article · 29 February 2024 · Science

DOI: https://doi.org/10.1126/science.adf7966 · OSTI ID:2470538

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Harvard Medical School, Boston, MA (United States)
Univ. of Wisconsin, Madison, WI (United States)
Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine
Altor Biosciences, Miramar, FL (United States)
National Institutes of Health (NIH), Bethesda, MD (United States)
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Santa Fe Inst. (SFI), Santa Fe, NM (United States)
ImmunityBio, Culver City, CA (United States)
Cornell Univ., Ithaca, NY (United States). Weill Medical College
Rockefeller Univ., New York, NY (United States)
Harvard Medical School, Boston, MA (United States); Boston College, Chestnut Hill, MA (United States)

The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)–infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Furthermore, upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb–treated macaques. Viral control was correlated with the reprogramming of CD8⁺T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 2470538

Journal Information:: Science, Journal Name: Science Journal Issue: 6687 Vol. 383; ISSN 0036-8075

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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