整合酶抑制剂在实际应用中的耐受性。

Tolerability of integrase inhibitors in a real-life setting.

作者信息

Peñafiel Judit, de Lazzari Elisa, Padilla Mireia, Rojas Jhon, Gonzalez-Cordon Ana, Blanco Jose L, Blanch Jordi, Marcos Maria A, Lonca Montserrat, Martinez-Rebollar Maria, Laguno Montserrat, Tricas Amparo, Rodriguez Ana, Mallolas Josep, Gatell Jose M, Martinez Esteban

机构信息

Hospital Clínic, University of Barcelona, Barcelona, Spain.

出版信息

J Antimicrob Chemother. 2017 Jun 1;72(6):1752-1759. doi: 10.1093/jac/dkx053.

DOI:10.1093/jac/dkx053

PMID:28333231

Abstract

BACKGROUND

Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them.

AIMS

We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients.

METHODS

Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit. Major outcomes were early discontinuation (≤1 year) due to any reason and more specifically due to toxicity. Incidence was calculated as number of episodes per 1000 person-years. Risk factors for discontinuation were assessed by multivariate Cox models.

RESULTS

Early discontinuations due to any reason were 271 (raltegravir), 168 (elvitegravir) and 264 (dolutegravir) per 1000 patient-years ( P = 0.0821). Early discontinuations due to toxicity were 76 (raltegravir), 103 (elvitegravir) and 81 (dolutegravir) per 1000 patient-years ( P = 0.6792). Overall, the most common toxicities leading to discontinuation were neuropsychiatric, osteomuscular or digestive. Most frequent neuropsychiatric manifestations reported at discontinuation were insomnia, dizziness, headache and anxiety irrespective of the integrase inhibitor. Among discontinuations due to toxicity, neuropsychiatric effects were more common with dolutegravir than with raltegravir or elvitegravir ( P = 0.0046). Age (HR 1.04, 95% CI 1.02-1.07, P = 0.0007) was the only independent risk factor for early discontinuation due to toxicity.

CONCLUSIONS

Discontinuations due to any reason tended to be less common with elvitegravir, but discontinuations due to toxicity did not differ among integrase inhibitors. Neuropsychiatric toxicity leading to drug discontinuation was more frequent with dolutegravir.

摘要

背景

在临床试验中，整合酶抑制剂已显示出比其他药物更好的耐受性，但一些上市后数据表明它们之间存在潜在差异。

目的

我们比较了在一大群感染艾滋病毒的患者中，基于拉替拉韦、埃替格韦和多替拉韦的治疗方案的停药率及原因。

方法

对一个前瞻性随访队列进行回顾性分析，该队列包括所有初治抗逆转录病毒治疗患者以及所有病毒学抑制的经治抗逆转录病毒治疗患者，这些患者接受了含拉替拉韦、埃替格韦或多替拉韦的首个治疗方案且至少有一次随访。主要结局是因任何原因导致的早期停药（≤1年），更具体地说是因毒性导致的停药。发病率计算为每1000人年的事件数。通过多变量Cox模型评估停药的危险因素。

结果

每1000患者年因任何原因导致的早期停药数分别为：拉替拉韦271例、埃替格韦168例、多替拉韦264例（P = 0.0821）。每1000患者年因毒性导致的早期停药数分别为：拉替拉韦76例、埃替格韦103例、多替拉韦81例（P = 0.6792）。总体而言，导致停药的最常见毒性是神经精神性、骨肌肉性或消化系统毒性。无论使用哪种整合酶抑制剂，停药时报告的最常见神经精神表现为失眠、头晕、头痛和焦虑。在因毒性导致的停药中，多替拉韦引起的神经精神效应比拉替拉韦或埃替格韦更常见（P = 0.0046）。年龄（风险比1.04，95%置信区间1.02 - 1.07，P = 0.0007）是因毒性导致早期停药的唯一独立危险因素。