Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Unità Operativa Complessa Malattie Infettive, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
PLoS One. 2019 Nov 21;14(11):e0225381. doi: 10.1371/journal.pone.0225381. eCollection 2019.
The study aimed to survey maraviroc use and assess effectiveness and durability of maraviroc-containing antiretroviral treatment (ART) in routine practice across Europe.
Data were retrieved from 26 cohorts in 8 countries comprising adults who started maraviroc in 2005-2016 and had ≥1 follow-up visit. Available V3 sequences were re-analysed centrally for tropism determination by geno2pheno[coreceptor]. Treatment failure (TF) was defined as either virological failure (viral load >50 copies/mL) or maraviroc discontinuation for any reason over 48 weeks. Predictors of TF were explored by logistic regression analysis. Time to maraviroc discontinuation was estimated by Kaplan-Meier survival analysis.
At maraviroc initiation (baseline), among 1,381 patients, 67.1% had experienced ≥3 ART classes and 45.6% had a viral load <50 copies/mL. Maraviroc was occasionally added to the existing regimen as a single agent (7.3%) but it was more commonly introduced alongside other new agents, and was often (70.4%) used with protease inhibitors. Accompanying drugs comprised 1 (40.2%), 2 (48.6%) or ≥3 (11.2%) ART classes. Among 1,273 patients with available tropism data, 17.6% showed non-R5 virus. Non-standard maraviroc use also comprised reported once daily dosing (20.0%) and a total daily dose of 150mg (12.1%). Over 48 weeks, 41.4% of patients met the definition of TF, although the 1-year estimated retention on maraviroc was 82.1% (95% confidence interval 79.9-84.2). Among 1,010 subjects on maraviroc at week 48, the viral load was >50 copies/mL in 19.9% and >200 copies/mL in 10.7%. Independent predictors of TF comprised a low nadir CD4 count, a detectable baseline viral load, previous PI experience, non-R5 tropism, having ≥3 active drugs in the accompanying regimen, and a more recent calendar year of maraviroc initiation.
This study reports on the largest observation cohort of patients who started maraviroc across 8 European countries. In this overall highly treatment-experienced population, with a small but appreciable subset that received maraviroc outside of standard treatment guidelines, maraviroc was safe and reasonably effective, with relatively low rates of discontinuation over 48 weeks and only 2 cases of serum transaminase elevations reported as reasons for discontinuation.
本研究旨在调查马拉维若在欧洲常规实践中的使用情况，并评估马拉维若为基础的抗逆转录病毒治疗（ART）的有效性和持久性。
数据来自 8 个国家的 26 个队列，包含 2005-2016 年开始使用马拉维若且至少有 1 次随访的成年人。对可用的 V3 序列进行中心重新分析，通过 geno2pheno[核心受体]确定趋化性。治疗失败（TF）定义为病毒载量>50 拷贝/mL（病毒载量失败）或 48 周内因任何原因停止使用马拉维若。通过逻辑回归分析探讨 TF 的预测因素。使用 Kaplan-Meier 生存分析估计马拉维若停药时间。
在马拉维若开始治疗（基线）时，1381 例患者中，67.1%有≥3 种 ART 类药物治疗史，45.6%病毒载量<50 拷贝/mL。马拉维若偶尔作为单一药物（7.3%）添加到现有方案中，但更常见的是与其他新药物一起使用，通常（70.4%）与蛋白酶抑制剂一起使用。伴随药物包括 1（40.2%）、2（48.6%）或≥3（11.2%）种 ART 类药物。在 1273 例有可用趋化性数据的患者中，17.6%显示非 R5 病毒。非标准马拉维若的使用还包括报告的每日一次剂量（20.0%）和 150mg 的总日剂量（12.1%）。48 周时，41.4%的患者符合 TF 定义，尽管 1 年的马拉维若保留率为 82.1%（95%置信区间 79.9-84.2）。在 48 周时接受马拉维若治疗的 1010 例患者中，病毒载量>50 拷贝/mL 的患者占 19.9%，>200 拷贝/mL 的患者占 10.7%。TF 的独立预测因素包括：CD4 计数最低、基线病毒载量可检测、既往 PI 治疗史、非 R5 趋化性、伴随治疗方案中有≥3 种活性药物、以及马拉维若开始治疗的最近日历年份。
本研究报告了在 8 个欧洲国家开始使用马拉维若的最大观察队列的患者。在这个整体高度治疗经验丰富的人群中，一小部分患者接受了不符合标准治疗指南的马拉维若治疗，马拉维若是安全且相对有效的，停药率相对较低，仅报告了 2 例因血清转氨酶升高而停药。
