临床免疫抑制剂和化疗药物对 HIV 的体外复制抑制作用。
Inhibition of HIV replication in vitro by clinical immunosuppressants and chemotherapeutic agents.
机构信息
National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, 10900, University Boulevard, Manassas, VA, USA.
出版信息
Cell Biosci. 2013 May 14;3(1):22. doi: 10.1186/2045-3701-3-22.
BACKGROUND
Recent studies have suggested that a functional cure for HIV-1 infection, purportedly resultant from allogeneic bone marrow transplantation, may be possible. Additionally, the first such patient was treated with whole-body irradiation, immunosuppressants, and the chemotherapeutic, cytarabine. However, the precise role of the coinciding medical interventions in diminishing detectable HIV reservoirs remains unstudied.
FINDINGS
In this article, we demonstrate that the immunosuppressants, mycophenolic acid and cyclosporine, and the chemotherapeutic, cytarabine, are potent antiretroviral agents at clinically relevant dosages. These drugs strongly inhibit HIV-1 replication in a GFP indicator T cell line and peripheral blood mononuclear cells (PBMC).
CONCLUSIONS
Our study suggests that certain clinical immunosuppressants and chemotherapeutic agents may act combinatorially to inhibit HIV infection. Additionally, chemotherapy-mediated cytotoxicity may also affect the stability of viral reservoirs. Thus, further study is needed to examine potential therapeutic value of these interventions in patients.
背景
最近的研究表明，异体骨髓移植可能会导致 HIV-1 感染的功能性治愈。此外，首例接受治疗的患者接受了全身放疗、免疫抑制剂和化疗药物阿糖胞苷。然而，在减少可检测到的 HIV 储存库方面，这些合并的医疗干预的确切作用仍未得到研究。
发现
在本文中，我们证明了免疫抑制剂霉酚酸和环孢菌素以及化疗药物阿糖胞苷在临床相关剂量下是有效的抗逆转录病毒药物。这些药物在 GFP 指示剂 T 细胞系和外周血单核细胞（PBMC）中强烈抑制 HIV-1 的复制。
结论
我们的研究表明，某些临床免疫抑制剂和化疗药物可能会联合作用抑制 HIV 感染。此外，化疗介导的细胞毒性也可能影响病毒储存库的稳定性。因此，需要进一步研究这些干预措施在患者中的潜在治疗价值。
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