Service de Maladies Infectieuses et Tropicales, Hôpital Saint-Louis-APHP, Paris, France INSERM U941, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
INSERM SC10, Villejuif, France.
J Antimicrob Chemother. 2015 Feb;70(2):562-5. doi: 10.1093/jac/dku395. Epub 2014 Oct 25.
Efavirenz and nevirapine failure is associated with a rapid selection of resistance-associated mutations (RAMs), which may impact on etravirine or rilpivirine susceptibility. However, RAMs for rilpivirine and etravirine cannot be reported on previous resistance genotypes because these specific RAMs were not analyzed at that time. Therefore, our objective was to determine, in virologically suppressed HIV-1-infected individuals, the presence of RAMs to rilpivirine, etravirine and the combination of tenofovir/emtricitabine/rilpivirine in HIV-1 DNA from individuals previously exposed to efavirenz and/or nevirapine.
The studied population included 169 treatment-experienced individuals enrolled in the ANRS 138-EASIER trial who previously failed on and/or were intolerant to efavirenz and/or nevirapine and who had plasma HIV-1 RNA<400 copies/mL. Resistance to rilpivirine, etravirine, tenofovir and emtricitabine by bulk sequencing was performed on extracted HIV-1 DNA from whole blood collected at the time of trial inclusion.
Reverse transcriptase gene amplification was successful in 128/169 (76%) individuals and 95% of HIV-1 were infected with subtype B. Rilpivirine RAMs were detected in 41 (32%) individuals, with highest frequency for the mutations Y181C/I/V (18%), K101E/P (7%) and E138A/G/K/Q/R/S (6%) and the association L100I+K103N/S (5%). Etravirine RAMs were detected in five (4%) individuals. Resistance to emtricitabine, tenofovir and at least one drug included in the combination of tenofovir/emtricitabine/rilpivirine were detected in 72 (56%), 12 (9%) and 88 (69%), respectively.
In individuals with suppressed viraemia under antiretroviral therapy (ART), but who had been previously exposed to an efavirenz and/or nevirapine-based regimen, rilpivirine RAMs are frequent and etravirine RAMs are rare. This finding suggests that the switch to a rilpivirine-based regimen should not be recommended.
依非韦伦和奈韦拉平耐药与耐药相关突变（RAMs）的快速选择相关，这可能影响依曲韦林或利匹韦林的敏感性。然而，由于当时没有分析这些特定的 RAMs，因此无法报告利匹韦林和依曲韦林的 RAMs。因此，我们的目的是在先前接受依非韦伦和/或奈韦拉平治疗的病毒学抑制的 HIV-1 感染者中，确定先前暴露于依非韦伦和/或奈韦拉平的个体中 HIV-1 DNA 中利匹韦林、依曲韦林和替诺福韦/恩曲他滨/利匹韦林组合的 RAMs 的存在。
研究人群包括 169 名曾接受过治疗的个体，他们参加了 ANRS 138-EASIER 试验，先前因依非韦伦和/或奈韦拉平耐药和/或不耐受而失败，且血浆 HIV-1 RNA<400 拷贝/ml。采用批量测序法对纳入试验时采集的全血中提取的 HIV-1 DNA 进行利匹韦林、依曲韦林、替诺福韦和恩曲他滨的耐药性检测。
169 名个体中有 128 名（76%）的逆转录酶基因扩增成功，95%的 HIV-1 感染了 B 亚型。在 41 名（32%）个体中检测到利匹韦林 RAMs，最常见的突变是 Y181C/I/V（18%）、K101E/P（7%）和 E138A/G/K/Q/R/S（6%），以及 L100I+K103N/S（5%）的关联。在 5 名（4%）个体中检测到依曲韦林 RAMs。在 72 名（56%）、12 名（9%）和 88 名（69%）个体中分别检测到对恩曲他滨、替诺福韦和包含在替诺福韦/恩曲他滨/利匹韦林组合中的至少一种药物的耐药性。
在接受抗逆转录病毒治疗（ART）的病毒血症受抑制的个体中，但曾接受过依非韦伦和/或奈韦拉平为基础的治疗方案，利匹韦林 RAMs 很常见，而依曲韦林 RAMs 很少见。这一发现表明，不应推荐改用利匹韦林为基础的方案。
