Laboratoire de Virologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UPMC University Paris 06, INSERM U943, Paris, France.
Antimicrob Agents Chemother. 2010 Feb;54(2):728-33. doi: 10.1128/AAC.01335-09. Epub 2009 Dec 14.
Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02_AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02_AG than in other non-B subtypes (P=0.004). Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. In conclusion, although the prevalence of ETR RAMs in treatment-naïve patients infected with non-B HIV-1 subtypes was 10%, in most cases this had no significant impact on ETR susceptibility. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility.
依发韦仑（ETR）易感性取决于非核苷类逆转录酶抑制剂（NNRTI）耐药相关突变（RAMs）的类型和数量。研究表明，一些 HIV-1 亚型可能存在天然的多态性，被描述为 ETR RAMs。本研究旨在探讨非 B 亚型 HIV-1 感染的初治患者中 ETR RAMs 的流行率及其对 ETR 易感性的潜在影响。研究了 726 例未接受过抗逆转录病毒治疗的感染非 B HIV-1 亚型的患者中 ETR RAMs 的流行率。根据法国国家艾滋病研究署和斯坦福算法解释 ETR 基因型耐药。对至少存在一个 ETR RAM 的样本进行 NNRTI 表型敏感性测定。总体而言，726 个序列中有 75 个（10.3%）携带至少一个 ETR RAM：72 名患者（10%）的序列各有一个 ETR RAM，3 名患者（0.4%）的序列各有两个 ETR RAM（一个病例中为 V90I 和 Y181C，另一个病例中为 V90I 和 A98G）。没有病毒携带三个或更多 ETR RAM，因此均未被归类为 ETR 耐药。所有携带两个 ETR RAM 的序列均属于 CRF02_AG 亚型。在携带一个 ETR RAM 的患者中，CRF02_AG 亚型比其他非 B 亚型更为常见（P=0.004）。鉴定出三种新的突变谱（E138A 和 V179I、Y181C 和 H221Y 以及 V90I 和 Y181C），表现出 ETR 表型敏感性降低。结论：尽管非 B HIV-1 亚型感染的初治患者中 ETR RAMs 的流行率为 10%，但在大多数情况下，这对 ETR 易感性没有显著影响。然而，在非 B 遗传背景下传播携带 Y181C 的耐药病毒可能对 ETR 易感性产生影响。
