Department of Infection & Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Future Microbiol. 2011 Mar;6(3):295-315. doi: 10.2217/fmb.11.7.
In this article, we summarize recent knowledge on drug-resistance mutations within HIV reverse transcriptase (RT). Several large-scale HIV-1 genotypic analyses have revealed that the most prevalent nucleos(t)ide analog RT inhibitor (NRTI)-resistance mutation is M184V/I followed by a series of thymidine analog-associated mutations: M41L, D67N, K70R, L210W, T215Y/F and K219Q/E. Among non-nucleoside RT inhibitor (NNRTI)-resistance mutations, K103N was frequently observed, followed by Y181C and G190A. Interestingly, V106M was identified in HIV-1 subtype C as a subtype-specific multi-NNRTI-resistance mutation. Regarding mutations in the HIV-1 RT C-terminal region, including the connection subdomain and RNase H domain, their clinical impacts are still controversial, although their effects on NRTI and NNRTI resistance have been confirmed in vitro. In HIV-2 infections, the high prevalence of the Q151M mutation associated with multi-NRTI resistance has been frequently observed.
在本文中，我们总结了 HIV 逆转录酶（RT）中耐药突变的最新知识。几项大规模的 HIV-1 基因型分析表明，最常见的核苷（酸）逆转录酶抑制剂（NRTI）耐药突变是 M184V/I，其次是一系列与胸苷类似物相关的突变：M41L、D67N、K70R、L210W、T215Y/F 和 K219Q/E。在非核苷逆转录酶抑制剂（NNRTI）耐药突变中，经常观察到 K103N，其次是 Y181C 和 G190A。有趣的是，V106M 被鉴定为 HIV-1 亚型 C 中的一种亚型特异性多 NNRTI 耐药突变。关于 HIV-1 RT C 末端区域的突变，包括连接亚结构域和 RNase H 结构域，尽管它们在体外已被证实对 NRTI 和 NNRTI 耐药性有影响，但它们的临床影响仍存在争议。在 HIV-2 感染中，经常观察到与多 NRTI 耐药相关的 Q151M 突变的高流行率。
