实现艾滋病治愈的障碍和策略。
Barriers and strategies to achieve a cure for HIV.
机构信息
The Peter Doherty Institute for Infection and Immunity, University of Melbourne, and Royal Melbourne Hospital, Melbourne, VIC, Australia.
Department of Infectious Diseases, Monash University, Alfred Hospital, Melbourne, VIC, Australia.
出版信息
Lancet HIV. 2018 Jun;5(6):e317-e328. doi: 10.1016/S2352-3018(18)30039-0.
Abstract
9 years since the report of a cure for HIV after C-C chemokine receptor type 5 Δ32 stem cell transplantation, no other case of HIV cure has been reported, despite much research. However, substantial progress has been made in understanding the biology of the latent HIV reservoir, and in measuring the amount of virus that persists after antiretroviral therapy (ART) with increasingly sophisticated approaches. This knowledge is being translated into a long pipeline of clinical trials seeking to reduce viral persistence in participants on suppressive treatment and ultimately to allow safe cessation of ART. In this Review, we discuss the main barriers preventing the development of an HIV cure, methods used to measure HIV persistence in individuals on ART, clinical strategies that aim to cure HIV, and future directions for studies in the field of HIV cure research.
摘要
自 C-C 趋化因子受体 5 Δ32 干细胞移植后治愈 HIV 的报告发布 9 年后，尽管进行了大量研究，但仍未报告其他治愈 HIV 的病例。然而，在理解潜伏 HIV 储库的生物学特性以及通过越来越复杂的方法测量抗逆转录病毒治疗 (ART) 后持续存在的病毒量方面，已经取得了实质性进展。这些知识正在转化为一系列临床试验，旨在减少接受抑制性治疗的参与者中的病毒持续存在，并最终允许安全停止 ART。在这篇综述中，我们讨论了阻止 HIV 治愈发展的主要障碍、用于测量接受 ART 的个体中 HIV 持续存在的方法、旨在治愈 HIV 的临床策略，以及 HIV 治愈研究领域的未来研究方向。
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2
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3
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