Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, laboratoire de virologie, F75013 Paris, France.
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F75013 Paris, France.
J Antimicrob Chemother. 2020 Jul 1;75(7):1943-1949. doi: 10.1093/jac/dkaa090.
The ANRS-163 ETRAL trial, a switch study to an etravirine 200 mg/raltegravir 400 mg twice-daily regimen in 165 patients with HIV-1 infection, showed durable efficacy until Week 96. The aim of this work was to investigate in detail the virological rebounds (VRs), defined as at least one plasma HIV viral load (VL) >50 copies/mL.
Quantification of HIV-DNA level was assessed at baseline, Week 48 and Week 96 (n = 157). VLs were measured in seminal plasma at Week 48 (n = 26). Genotypic resistance testing by ultra-deep sequencing (UDS) for reverse transcriptase (RT) and integrase regions was performed at baseline and at the time of VR.
In this study, 19 patients experienced VR, with 2 patients having virological failure (VF; two consecutive VLs >50 copies/mL). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). For the second patient with VF, neither RT nor integrase mutations were detected at baseline and VF. Median HIV-DNA level was similar at baseline, Week 48 and Week 96 (2.17, 2.06 and 2.11 log10 copies/106 cells, respectively). Only one patient had a detectable seminal HIV VL (505 copies/mL).
The dual etravirine/raltegravir regimen as maintenance therapy was effective and the emergence of mutations in cases of VF was similar to that seen in other dual-regimen studies. No HIV-DNA level modification was evidenced by Week 96.
ANRS-163 ETRAL 试验是一项转换研究，165 例 HIV-1 感染患者由每日两次依曲韦林 200mg/拉替拉韦 400mg 方案转换为该方案，结果显示直至第 96 周仍具有持久疗效。本研究旨在详细分析病毒学反弹（VR），即至少一次血浆 HIV 病毒载量（VL）>50 拷贝/ml。
在基线、第 48 周和第 96 周（n=157）时评估 HIV-DNA 水平。在第 48 周（n=26）时检测精液中 VL。在基线和 VR 时通过超深度测序（UDS）进行逆转录酶（RT）和整合酶区域的基因型耐药性检测。
本研究中 19 例患者出现 VR，2 例患者发生病毒学失败（VF；连续两次 VL>50 拷贝/ml）。对于第 1 例 VF 患者，UDS 在基线时仅检测到 RT 中少数耐药变异（K103N，9.6%；Y181C，4.9%）。在 VF 时，一些 RT 变异成为主要变异（K101E，86.3%；Y181C，100.0%；G190A，100.0%），而其他变异出现在整合酶中（Y143C，2.4%；Q148R，6.2%；N155H，18.8%）。对于第 2 例 VF 患者，基线和 VF 时均未检测到 RT 或整合酶突变。基线、第 48 周和第 96 周时 HIV-DNA 中位数水平相似（分别为 2.17、2.06 和 2.11 log10 拷贝/106 细胞）。仅有 1 例患者的精液 HIV VL 可检测到（505 拷贝/ml）。
依曲韦林/拉替拉韦双联维持治疗方案有效，VF 病例中突变的出现与其他双联治疗研究相似。第 96 周时未发现 HIV-DNA 水平改变。
