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

• 成果类型: Article
• 署名作者: 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.
• 署名单位: Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; University of Wisconsin System; University of Wisconsin Madison; Johns Hopkins University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); United States Department of Energy (DOE); Los Alamos National Laboratory; Johns Hopkins University; Howard Hughes Medical Institute; Cornell University; Weill Cornell Medicine; Rockefeller University; Howard Hughes Medical Institute; Rockefeller University; Boston College; Emory University; NewYork-Presbyterian Hospital; Columbia University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12476
• DOI: 10.1126/science.adf7966
• 发表日期: 2024-03-08
• 页码: 1104-1111
• 关键词: cd4(+) t-cells; rhesus macaques; hiv-1; siv; responses; assay; reservoir; therapy

摘要

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. 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.