Department of Biomedical Sciences, University of Catania, Italy.
Br J Clin Pharmacol. 2010 Dec;70(6):784-93. doi: 10.1111/j.1365-2125.2010.03735.x.
The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1 replication in vitro through different mechanisms including, but not limited, to down regulation of CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also inhibits HIV-1 infection in human peripheral blood leucocytes-SCID reconstituted mice. In addition, a prospective nonrandomized trial of HIV patient series receiving RAPA monotherapy after liver transplantation indicated significantly better control of HIV and hepatitis C virus (HCV) replication among patients taking RAPA monotherapy. Taken together, the evidence presented in this review suggests that RAPA may be a useful drug that should be evaluated for the prevention and treatment of HIV-1 infection.
开发替代抗 HIV 药物的强烈需求主要归因于耐药病毒的出现、对复杂治疗方案持续坚持的需求以及现有抗病毒药物的毒性。本综述分析了概念验证研究的结果，表明免疫调节剂雷帕霉素（RAPA）具有体外和体内抗 HIV 的特性，使其有资格成为一种潜在的新型抗 HIV 药物。这是对评估 RAPA 在 HIV 中体外和体内活性的已发表研究的文献综述。RAPA 通过不同的机制抑制 HIV-1 的复制，包括但不限于下调 CCR5。此外，RAPA 还协同增强了进入抑制剂（如 vicriviroc、aplaviroc 和 enfuvirtide）的抗 HIV 活性。RAPA 还抑制了人类外周血白细胞-SCID 重建小鼠中的 HIV-1 感染。此外，一项对接受肝移植后接受 RAPA 单药治疗的 HIV 患者系列的前瞻性非随机试验表明，接受 RAPA 单药治疗的患者 HIV 和丙型肝炎病毒（HCV）复制的控制明显更好。综上所述，本综述中提出的证据表明，RAPA 可能是一种有用的药物，值得评估其在预防和治疗 HIV-1 感染中的应用。
