Institute for Medical Virology, Johann Wolfgang Goethe-University Hospital, Paul-Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
J Clin Virol. 2012 Mar;53(3):248-50. doi: 10.1016/j.jcv.2011.12.012. Epub 2011 Dec 30.
Analysis of the 3D structure of the HIV-1 reverse transcriptase led to the development of TMC278 (rilpivirine), a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), which proved to be effective against wild-type HIV-1 strains and NNRTI-resistant mutants emerging after failure of NNRTI-containing therapy regimens. Recently, rilpivirine associated mutations (e.g. at positions 138, 181 or 101) have been described in vitro and in vivo; however, some of these mutations have also been observed in the past.
Objective of our investigation was to determine the prevalence of mutations E138K, Y181I/V, and K101E/P before the approval of rilpivirine.
The Frankfurt Resistance Database consists of 7295 samples which have been sent for resistance testing since 1995.
The E138K, Y181I/V, and the K101E mutations were found in 0.4%, 0.9%, and 2.4% of the patients, respectively.
Based on these findings we do not expect a broad cross-resistance to rilpivirine due to previous treatment failures of NNRTI-containing regimens.
对 HIV-1 逆转录酶的 3D 结构进行分析，导致了 TMC278（利匹韦林）的开发，这是一种下一代非核苷类逆转录酶抑制剂（NNRTI），对野生型 HIV-1 株和 NNRTI 治疗方案失败后出现的 NNRTI 耐药突变体均有效。最近，已在体外和体内描述了利匹韦林相关突变（例如位置 138、181 或 101）；然而，其中一些突变过去也曾被观察到过。
我们研究的目的是确定在批准利匹韦林之前 E138K、Y181I/V 和 K101E/P 突变的流行率。
法兰克福耐药数据库包含自 1995 年以来为耐药检测而送检的 7295 个样本。
E138K、Y181I/V 和 K101E 突变分别在 0.4%、0.9%和 2.4%的患者中被发现。
基于这些发现，我们预计由于之前 NNRTI 治疗方案失败，不会出现广泛的交叉耐药。
