Schwartz Christian, Bouchat Sophie, Marban Céline, Gautier Virginie, Van Lint Carine, Rohr Olivier, Le Douce Valentin
University of Strasbourg, EA7292, DHPI, Institute of Parasitology and Tropical Pathology, Strasbourg, France; University of Strasbourg, IUT Louis Pasteur, Schiltigheim, France.
Université Libre de Bruxelles (ULB), Service of Molecular Virology, Institute for Molecular Biology and Medicine (IBMM), 12 rue des Profs Jeener et Brachet, 6041 Gosselies, Belgium.
Biochem Pharmacol. 2017 Dec 15;146:10-22. doi: 10.1016/j.bcp.2017.07.001. Epub 2017 Jul 4.
Introduction of cART in 1996 has drastically increased the life expectancy of people living with HIV-1. However, this treatment has not allowed cure as cessation of cART is associated with a rapid viral rebound. The main barrier to the eradication of the virus is related to the persistence of latent HIV reservoirs. Evidence is now accumulating that purging the HIV-1 reservoir might lead to a cure or a remission. The most studied strategy is the so called "shock and kill" therapy. This strategy is based on reactivation of dormant viruses from the latently-infected reservoirs (the shock) followed by the eradication of the reservoirs (the kill). This review focuses mainly on the recent advances made in the "shock and kill" therapy. We believe that a cure or a remission will come from combinatorial approaches i.e. combination of drugs to reactivate the dormant virus from all the reservoirs including the one located in sanctuaries, and combination of strategies boosting the immune system. Alternative strategies based on cell and gene therapy or based in inducing deep latency, which are evoked in this review reinforce the idea that at least a remission is attainable.
1996年开始使用的抗逆转录病毒疗法(cART)极大地延长了HIV-1感染者的预期寿命。然而,这种治疗方法尚未实现治愈,因为停止使用cART会导致病毒迅速反弹。根除病毒的主要障碍与潜伏性HIV储存库的持续存在有关。现在越来越多的证据表明,清除HIV-1储存库可能会实现治愈或缓解。研究最多的策略是所谓的“激活并清除”疗法。该策略基于从潜伏感染的储存库中重新激活休眠病毒(激活),然后清除储存库(清除)。本综述主要关注“激活并清除”疗法的最新进展。我们相信,治愈或缓解将来自联合方法,即联合使用药物从所有储存库(包括位于免疫赦免部位的储存库)中重新激活休眠病毒,以及联合使用增强免疫系统的策略。本综述中提到的基于细胞和基因疗法或诱导深度潜伏的替代策略强化了至少可以实现缓解的观点。