de Goede A L, Vulto A G, Osterhaus A D M E, Gruters R A
Department of Viroscience, Erasmus MC, 's-Gravendijkwal 230, PO box 2040, 3000 CA Rotterdam, The Netherlands; Department of Hospital Pharmacy, Erasmus MC, 's-Gravendijkwal 230, PO box 2040, 3000 CA Rotterdam, The Netherlands.
Department of Hospital Pharmacy, Erasmus MC, 's-Gravendijkwal 230, PO box 2040, 3000 CA Rotterdam, The Netherlands.
Ann Pharm Fr. 2015 May;73(3):169-79. doi: 10.1016/j.pharma.2014.11.003. Epub 2014 Dec 17.
HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies.
HIV感染会导致具有免疫能力的CD4(+) T淋巴细胞逐渐丧失，并发展为艾滋病。联合抗逆转录病毒药物（cART）进行有效治疗可将病毒载量降低至检测不到的水平，但无法从体内清除病毒。cART的成功受到昂贵的终身服药要求、累积的药物毒性以及慢性免疫激活的阻碍，即使病毒复制受到抑制，这也会增加患几种非艾滋病疾病的风险。因此，迫切需要替代cART的治疗策略。免疫疗法或治疗性疫苗接种旨在增强现有的针对HIV的免疫反应或诱导全新的免疫反应。这些免疫反应应通过在不使用cART的情况下控制病毒复制和预防疾病进展来实现功能性治愈。开发HIV疫苗的关键困难在于我们对控制病毒复制的免疫反应一无所知，因此也不知道如何引发这些反应以及如何对其进行监测。本综述的第一部分对HIV感染的（病理）生理学进行了广泛概述。它描述了HIV的结构和复制周期、HIV感染的流行病学和发病机制以及针对HIV的固有免疫和适应性免疫反应。本综述的第二部分讨论了HIV的治疗选择。简要介绍了预防方式和抗逆转录病毒疗法，之后对HIV疫苗接种策略进行了广泛概述，包括免疫原的选择和递送策略。
