Pharmaceutical approaches to eradication of persistent HIV infection
Pharmaceutical approaches to eradication of persistent HIV infection
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DOI：
10.1017/s1462399409000970
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发表时间：
2009-02-11
影响因子：
6.2
通讯作者：
Margolis, David M.
中科院分区：
文献类型：
--
作者：
Bowman, Mary-Catherine;Archin, Nancie M.;Margolis, David M.
在发达国家，高效抗逆转录病毒疗法（HAART）显著降低了人类免疫缺陷病毒1型（HIV-1）感染者的发病率和死亡率。成功的治疗通常导致HIV-1 RNA的稳定血浆水平低于商业检测的检测限。尽管如此，HIV-1还没有被HAART治愈。在目前的治疗中，HIV感染持续存在的原因似乎是多方面的：静息CD 4（+）T细胞中潜伏但具有复制能力的前病毒，低于临床检测检测限的隐蔽病毒表达，以及病毒避难所位点都可能导致持续存在。清除HIV感染几乎肯定需要一种多模式方法，包括有效抑制HIV复制，达到残留HIV复制的所有隔室的治疗以及消除任何持续性、静止性前病毒感染的储存库。这篇综述强调了建立和维持病毒库的基本机制以及消除病毒库的药物方法。
Highly active antiretroviral therapy (HAART) has markedly decreased morbidity and mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals in the developed world. Successful therapy often results in stable plasma levels of HIV-1 RNA below the limits of detection of commercial assays. Nonetheless, HIV-1 has not been cured by HAART. The causes of persistence of HIV infection in the face of current therapy appear to be multifactorial: latent but replication-competent provirus in resting CD4(+) T cells, cryptic viral expression below the limits of detection of clinical assays, and viral sanctuary sites might all contribute to persistence. Clearance of HIV infection will almost certainly require a multimodality approach that includes potent suppression of HIV replication, therapies that reach all compartments of residual HIV replication and depletion of any reservoirs of persistent, quiescent proviral infection. This review highlights the basic mechanisms for the establishment and maintenance of viral reservoirs and pharmaceutical approaches towards their elimination.