美国哈佛大学医学院James B. Whitney团队取得一项新突破。他们的研究发现在SHIV感染的抗逆转录病毒疗法（ART）耐受的猕猴中，双重免疫治疗可持续缓解病情。该项研究成果发表在2024年2月29日出版的《科学》上。

据了解，根除病毒库是临床治愈HIV-1感染的主要障碍。研究人员证明在停止抗逆转录病毒治疗后，给予Anktiva（N-803）和广谱中和抗体（bNAbs），可持续控制感染SHIV-AD8且ART耐受猕猴体内的病毒。

N-803⁺bNAbs治疗可诱导免疫激活和短暂的病毒血症，但只能有限地减少SHIV病毒库。在停止抗逆转录病毒疗法后，所有动物体内的病毒含量都会反弹，而在所有接受过N-803⁺bNAb治疗的猕猴中，约有70%猕猴体内的病毒得到了持久控制。

病毒控制和N-803⁺bNAb与CD8⁺ T细胞重编程的协同作用有关。因此，彻底清除具有复制能力的病毒库，可能并不是停用抗逆转录病毒疗法后诱导持续缓解的先决条件。

附：英文原文

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

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

Issue&Volume: 2024-02-29

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 Anktiva (N-803) and broadly neutralizing antibodies (bNAbs) resulted in sustained viral control after discontinuation of antiretroviral therapy (ART) in 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 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.

DOI: adf7966

Source: https://www.science.org/doi/10.1126/science.adf7966