Abdi Basma, Palich Romain, Seang Sophie, Fauchois Antoine, Cocherie Théophile, Faycal Antoine, Sayon Sophie, Teyssou Elisa, Saliba Sanaa, Soulie Cathia, Valantin Marc Antoine, Pourcher Valérie, Katlama Christine, Calvez Vincent, Marcelin Anne-Geneviève, Wirden Marc
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), AP-HP, Hôpital Pitié Salpêtrière, Service des Maladies Infectieuses et Tropicales, Paris, France.
JAC Antimicrob Resist. 2024 Dec 5;6(6):dlae194. doi: 10.1093/jacamr/dlae194. eCollection 2024 Dec.
We assessed the kinetics of the clearance of integrase strand transfer inhibitors resistance mutations (INSTIs-RMs) and associated factors from people living with HIV (PWH) displaying suppressed viral replication after virological failure (VF) on an INSTI regimen.
We included PWH with HIV-RNA viral loads ≤20 copies/mL for at least 5 years in whom INSTIs-RM had been identified at least once in a prior RNA resistance genotyping test. HIV DNAs were sequenced by Sanger sequencing (SS) and ultra-deep sequencing (UDS; detection threshold: 5%) every year over the preceding 5 years.
We included 39 PWH in the study. Most (95%) had experienced VF on a raltegravir-containing regimen. The past INSTIs-RMs were not detected in the peripheral blood mononuclear cells of 35 of the 39 (90%) PWH by SS at the end of follow-up. In a longitudinal analysis (2017-21) based on UDS, the previously detected INSTIs-RMs were not detected in 29 of the 35 (83%) PWH. In multivariable analysis, the duration of viral replication and the level of HIV-RNA during prior VF were significantly associated with the persistence of INSTIs-RM, with odds ratios of 1.05 per week of replication (95% CI, 1.00-1.11; = 0.024) and 8.26 per log copies/mL (95% CI, 1.46-46.59; = 0.017).
We observed a clear trend towards the clearance of archived INSTIs-RM after a long period of virological control leading to changes in the resistance profile in cellular DNA, raising the possibility of studies assessing the recycling of INSTI classes even in the presence of a history of resistance.
我们评估了整合酶链转移抑制剂耐药突变（INSTIs-RMs）的清除动力学以及来自在基于整合酶链转移抑制剂（INSTI）方案的病毒学失败（VF）后病毒复制受到抑制的HIV感染者（PWH）的相关因素。
我们纳入了HIV-RNA病毒载量≤20拷贝/mL至少5年且在先前的RNA耐药基因分型检测中至少一次鉴定出INSTIs-RM的PWH。在过去5年中，每年通过桑格测序（SS）和超深度测序（UDS；检测阈值：5%）对HIV DNA进行测序。
我们在研究中纳入了39名PWH。大多数（95%）曾在含raltegravir的方案中经历病毒学失败。在随访结束时，通过SS在39名PWH中的35名（90%）的外周血单个核细胞中未检测到既往的INSTIs-RMs。在基于UDS的纵向分析（2017 - 2021年）中，在35名PWH中的29名（83%）中未检测到先前检测到的INSTIs-RMs。在多变量分析中，先前病毒学失败期间的病毒复制持续时间和HIV-RNA水平与INSTIs-RM的持续存在显著相关，复制每周的比值比为1.05（95%CI，1.05 - 1.11；P = 0.024），每log拷贝/mL为8.26（95%CI，1.46 - 46.59；P = 0.017）。
我们观察到在长期病毒学控制后，存档的INSTIs-RM清除有明显趋势，导致细胞DNA耐药谱发生变化，这增加了即使在存在耐药史的情况下评估整合酶链转移抑制剂类药物再利用研究的可能性。
