Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy
Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy
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DOI：
10.1172/jci200214522
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发表时间：
2002-03-01
影响因子：
15.9
通讯作者：
Pantaleo, G
中科院分区：
文献类型：
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作者：
Rizzardi, GP;Harari, A;Pantaleo, G
原发性HIV-1感染引起广泛的免疫激活，在此期间，CD 4（+）T细胞激活支持大量HIV-1产生。我们测试的安全性和免疫调节作用的联合环孢素A（CsA）治疗与高效抗逆转录病毒疗法（HAART）在原发性HIV-1感染。9名原发性HIV-1感染的成人接受了CsA沿着HAART治疗。在第8周，所有患者停用CsA，但维持HAART。在CsA + HAART队列和29例仅用HAART治疗原发性感染的对照患者中，病毒复制受到相当程度的抑制。CsA恢复正常的CD 4（+）T细胞水平，无论是在百分比和绝对数量。CD 4（+）T细胞的增加在一周内明显，并持续整个研究期间。CsA对病毒特异性CD 8（+）或CD 4（+）T细胞应答无损害。在第48周，CsA + HAART队列中分泌IFN-γ的CD 4（+）和CD 4（+）CCR 7（-）T细胞的比例显著高于HAART单独队列。总之，在原发性HIV-1感染的早期阶段快速关闭T细胞活化可以产生长期的有益效果，并建立更有利的免疫设定点。适当的，基于免疫的治疗干预可能是一个有价值的补充HAART治疗艾滋病毒感染。
Primary HIV-1 infection causes extensive immune activation, during which CD4(+) T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4(+) T cell levels, both in terms of percentage and absolute numbers. The increase in CD4(+) T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8(+) or CD4(+) T cell responses. At week 48, the proportion of IFN-gamma-secreting CD4(+) and CD4(+)CCR7(-) T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection.