Division of Infection and Immunity, University College London, London, UK.
Institute of Human Virology, Abuja, Nigeria.
J Antimicrob Chemother. 2019 May 1;74(5):1402-1407. doi: 10.1093/jac/dkz005.
Previous work showed that gag-protease-derived phenotypic susceptibility to PIs differed between HIV-1 subtype CRF02_AG/subtype G-infected patients who went on to successfully suppress viral replication versus those who experienced virological failure of lopinavir/ritonavir monotherapy as first-line treatment in a clinical trial. We analysed the relationship between PI susceptibility and outcome of second-line ART in Nigeria, where subtypes CRF02_AG/G dominate the epidemic.
Individuals who experienced second-line failure with ritonavir-boosted PI-based ART were matched (by subtype, sex, age, viral load, duration of treatment and baseline CD4 count) to those who achieved virological response ('successes'). Successes were defined by viral load <400 copies of HIV-1 RNA/mL by week 48. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with PI susceptibility expressed as IC50 fold change (FC) relative to a subtype B reference strain.
The median (IQR) lopinavir IC50 FC was 4.04 (2.49-7.89) for virological failures and 4.13 (3.14-8.17) for virological successes (P = 0.94). One patient had an FC >10 for lopinavir at baseline and experienced subsequent virological failure with ritonavir-boosted lopinavir as the PI. There was no statistically significant difference in single-round replication efficiency between the two groups (P = 0.93). There was a moderate correlation between single-round replication efficiency and FC for lopinavir (correlation coefficient 0.32).
We found no impact of baseline HIV-1 Gag-protease-derived phenotypic susceptibility on outcomes of PI-based second-line ART in Nigeria.
先前的研究表明，在接受洛匹那韦/利托那韦单药一线治疗的 HIV-1 型 CRF02_AG/亚型 G 感染者中，成功抑制病毒复制的患者与发生病毒学失败的患者之间， gag 蛋白酶衍生的对蛋白酶抑制剂（PI）的表型敏感性存在差异。本研究分析了尼日利亚（CRF02_AG/G 亚型占主导地位）接受二线抗逆转录病毒治疗（ART）的个体中，PI 敏感性与治疗结局的关系。
对接受利托那韦增强的 PI 为基础的 ART 二线治疗失败的个体（根据亚型、性别、年龄、病毒载量、治疗持续时间和基线 CD4 计数进行匹配）与实现病毒学应答（“成功”）的个体进行匹配。成功定义为在第 48 周时 HIV-1 RNA 病毒载量<400 拷贝/ml。从患者样本中扩增全长 gag 蛋白酶，用于体外表型药敏试验，PI 敏感性用相对于亚型 B 参考株的 IC50 倍变化（FC）表示。
病毒学失败患者的洛匹那韦 IC50 FC 的中位数（IQR）为 4.04（2.49-7.89），病毒学成功患者的洛匹那韦 IC50 FC 为 4.13（3.14-8.17）（P=0.94）。有 1 名患者基线时洛匹那韦的 FC>10，在利托那韦增强的洛匹那韦作为 PI 治疗时发生了随后的病毒学失败。两组之间单轮复制效率无统计学差异（P=0.93）。单轮复制效率与洛匹那韦的 FC 之间存在中度相关性（相关系数 0.32）。
本研究未发现基线 HIV-1 gag 蛋白酶衍生的表型敏感性对尼日利亚接受 PI 为基础的二线 ART 治疗结局有影响。
