Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques
So‐Yon Lim, Jina Lee, Christa E. Osuna, Pratik Vikhe, Dane Schalk, Elsa Chen, Emily J. Fray, Mithra R. Kumar, Nancy Schultz‐Darken, Eva G. Rakasz, Saverio Capuano, Ruby A. Ladd, Hwi Min Gil, David T. Evans, Emily K. Jeng, Michael S. Seaman, Malcolm A. Martin, Christiaan H. van Dorp, Alan S. Perelson, Hing C. Wong, Janet D. Siliciano, Robert F. Siliciano, Jeffrey T. Safrit, Douglas F. Nixon, Patrick Soon‐Shiong, Michel C. Nussenzweig, James B. Whitney
Abstract
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.