INSERM, Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, laboratoire de virologie, Paris, France.
INSERM, Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
J Antimicrob Chemother. 2024 Aug 1;79(8):1974-1984. doi: 10.1093/jac/dkae194.
Doravirine is the latest NNRTI to be approved for the treatment of HIV-1 and has a different resistance profile from first-generation NNRTIs. Our aim was to investigate the virological efficacy of antiretroviral treatment including doravirine in people living with HIV-1 (PLWHIV), the factors associated with virological failure (VF) and those associated with the emergence of reverse transcriptase (RT) mutations in the case of VF.
A retrospective national survey of PLWHIV who were either naive or experienced on antiretroviral treatment including doravirine was conducted. VF was defined as two consecutive plasma viral loads (VLs) of ≥50 copies/mL or one VL of ≥200 copies/mL. Genotypic resistance tests were interpreted using the Stanford (v9.4.1) and ANRS (v33) algorithms.
Of the 589 PLWHIV treated with a doravirine-containing regimen, 8.5% were naive and 91.5% had prior antiretroviral experience; 56.9% were infected with HIV-1 B subtype. Overall, 88.3% and 85.1% of participants were virologically controlled at Month (M)3 and M6 of doravirine treatment, respectively. In multivariable analysis, CRF02_AG subtype, higher zenith plasma HIV-1 RNA VL, doravirine initiation in the context of failure and baseline V179D mutation presence were associated with VF. Among 88 PLWHIV who experienced virological failure at M6, 15.9% had a median of 2 (IQR 1-3) HIV RT mutations. In multivariable analysis, the only factor associated with the occurrence of mutations was a genotypic sensitivity score that was not fully sensitive.
This study is one of the largest to characterize the virological efficacy of doravirine-containing regimens in clinical practice and to identify factors associated with VF or emergence of resistance mutations that should be considered in clinical management.
多伟拉韦是最新被批准用于治疗 HIV-1 的 NNRTI，与第一代 NNRTI 相比具有不同的耐药谱。我们的目的是研究包含多伟拉韦的抗逆转录病毒治疗在 HIV-1 感染者（PLWHIV）中的病毒学疗效，以及与病毒学失败（VF）相关的因素，以及与 VF 情况下逆转录酶（RT）突变出现相关的因素。
对接受包含多伟拉韦的抗逆转录病毒治疗的 PLWHIV 进行了一项回顾性全国性调查。VF 定义为两次连续的血浆病毒载量（VL）≥50 拷贝/ml 或一次 VL≥200 拷贝/ml。使用斯坦福大学（v9.4.1）和法国国家艾滋病研究署（v33）算法对基因型耐药性检测进行解释。
在接受多伟拉韦治疗方案的 589 名 PLWHIV 中，8.5%为初治，91.5%有既往抗逆转录病毒治疗史；56.9%感染 HIV-1 B 亚型。总体而言，分别有 88.3%和 85.1%的患者在多伟拉韦治疗的第 3 个月和第 6 个月病毒学得到控制。多变量分析显示，CRF02_AG 亚型、较高的 HIV-1 RNA 病毒载量、多伟拉韦在失败背景下的起始治疗和基线 V179D 突变的存在与 VF 相关。在 88 名在第 6 个月时发生病毒学失败的 PLWHIV 中，15.9%有中位数为 2（IQR 1-3）个 HIV RT 突变。多变量分析显示，唯一与突变发生相关的因素是基因型敏感性评分不完全敏感。
这项研究是描述多伟拉韦治疗方案在临床实践中的病毒学疗效并确定与 VF 或耐药突变出现相关的因素的最大研究之一，这些因素应在临床管理中加以考虑。
