Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de virologie, Paris, France.
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié Salpêtrière, Service de maladies infectieuses, Paris, France.
J Antimicrob Chemother. 2018 Aug 1;73(8):2141-2146. doi: 10.1093/jac/dky130.
To investigate the dynamics of HIV-1 variants archived in cells harbouring drug resistance-associated mutations (DRAMs) to lamivudine/emtricitabine, etravirine and rilpivirine in patients under effective ART free from selective pressure on these DRAMs, in order to assess the possibility of recycling molecules with resistance history.
We studied 25 patients with at least one DRAM to lamivudine/emtricitabine, etravirine and/or rilpivirine identified on an RNA sequence in their history and with virological control for at least 5 years under a regimen excluding all drugs from the resistant class. Longitudinal ultra-deep sequencing (UDS) and Sanger sequencing of the reverse transcriptase region were performed on cell-associated HIV-1 DNA samples taken over the 5 years of follow-up.
Viral variants harbouring the analysed DRAMs were no longer detected by UDS over the 5 years in 72% of patients, with viruses susceptible to the molecules of interest found after 5 years in 80% of patients with UDS and in 88% of patients with Sanger. Residual viraemia with <50 copies/mL was detected in 52% of patients. The median HIV DNA level remained stable (2.4 at baseline versus 2.1 log10 copies/106 cells 5 years later).
These results show a clear trend towards clearance of archived DRAMs to reverse transcriptase inhibitors in cell-associated HIV-1 DNA after a long period of virological control, free from therapeutic selective pressure on these DRAMs, reflecting probable residual replication in some reservoirs of the fittest viruses and leading to persistent evolution of the archived HIV-1 DNA resistance profile.
在未对耐药相关突变（DRAMs）施加药物选择压力的情况下，研究携带拉米夫定/恩曲他滨、依曲韦林和利匹韦林耐药相关 DRAMs 的细胞中 HIV-1 变异体的动态变化，以评估具有耐药史的分子回收的可能性。
我们研究了 25 名患者，他们在病史中有至少一个 DRAMs（针对拉米夫定/恩曲他滨、依曲韦林和/或利匹韦林），在排除耐药类所有药物的方案下，经过至少 5 年的病毒学控制，实现了病毒学控制。在 5 年的随访期间，对细胞相关 HIV-1 DNA 样本进行了纵向超深度测序（UDS）和逆转录酶区的 Sanger 测序。
在 72%的患者中，UDS 在 5 年内未检测到携带分析 DRAMs 的病毒变异体，80%的 UDS 患者和 88%的 Sanger 患者在 5 年后发现了对感兴趣分子敏感的病毒。52%的患者检测到残留的<50 拷贝/ml 的病毒血症。中位 HIV DNA 水平保持稳定（基线时为 2.4，5 年后为 2.1 log10 拷贝/106 细胞）。
这些结果表明，在未对这些 DRAMs 施加治疗性选择压力的情况下，经过长期的病毒学控制，细胞相关 HIV-1 DNA 中逆转录酶抑制剂的耐药相关 DRAMs 明显清除，反映了最适病毒在某些储库中可能存在残留复制，并导致储存的 HIV-1 DNA 耐药谱持续进化。
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