Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA.
Science. 2024 Mar 8;383(6687):1104-1111. doi: 10.1126/science.adf7966. Epub 2024 Feb 29.
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.
消除病毒储存库是开发针对已建立的 HIV-1 感染的临床治愈方法的主要障碍。在这里，我们证明在受感染的恒河猴（ART 抑制的 SHIV-AD8）中，停止抗逆转录病毒治疗（ART）后，N-803（商品名 Anktiva）和广泛中和抗体（bNAb）的给药可导致持续的病毒控制。N-803+bNAb 治疗诱导免疫激活和短暂的病毒血症，但对 SHIV 储存库的减少有限。停止 ART 后，所有动物均发生病毒反弹，随后在接受 N-803+bNAb 治疗的大约 70％的所有恒河猴中均出现持久控制。病毒控制与 N-803+bNAb 协同作用对 CD8 T 细胞的重新编程有关。因此，完全消除复制能力的病毒储存库可能不是在停止 ART 后诱导持续缓解的必要条件。
