Association of raltegravir use with long-term health outcomes in HIV-infected patients: an observational post-licensure safety study in a large integrated healthcare system.

Q2 Medicine
HIV Clinical Trials Pub Date : 2018-10-01 Epub Date: 2018-10-27 DOI:10.1080/15284336.2018.1523826
Michael A Horberg, Allison H Oakes, Leo B Hurley, William J Towner, Chun R Chao, Michael J Silverberg, Jean Q Chantra, Courtney G Ellis, Charles P Quesenberry
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引用次数: 6

Abstract

Background: Raltegravir became the first integrase inhibitor to gain FDA approval; but with limited evidence documenting long-term risks in real world care, especially for major health outcomes of interest.

Objective: Assess raltegravir safety in clinical practice within an integrated health system.

Methods: We conducted a cohort study of HIV-infected adults within Kaiser Permanente California from 2005 to 2013. We compared patients initiating raltegravir during the study period with two groups; a historical cohort (started new antiretroviral regimen [ART] 2005-2007) and a concurrent cohort that did not initiate raltegravir (2007-2013). We used multivariate Cox proportional hazard regression to obtain hazard ratios (HR) for pre-specified incident health outcomes, employing propensity scores to adjust for potential confounding.

Results: The population included 8,219 HIV-infected adults (raltegravir cohort N = 1,757; 4,798 patient-years), with greater years known HIV-infected among raltegravir patients. The raltegravir cohort had increased HR for AIDS-defining (HR 2.69 [1.53-4.71]; HR 1.85 [1.21-2.82]) and non-AIDS-defining malignancies (HR 2.26 [1.29-3.94]; HR 1.88 [1.26-2.78]) relative to both comparison cohorts. Compared to the historical cohort we found no significant difference in all-cause mortality; the raltegravir cohort experienced increased HR for all-cause mortality compared to concurrent (HR 1.53 [1.02-2.31]). Raltegravir appeared protective of lipodystrophy when compared to the historical cohort but associated with increased incidence compared to concurrent. There were no significant differences in the incidence of hepatic, skin, or cardiovascular events.

Conclusions: The potentially elevated risk for malignancy and mortality with raltegravir and residual confounding merits further investigation. We demonstrate the value of observational cohorts for monitoring post-licensure medication safety.

在hiv感染患者中使用雷替韦韦与长期健康结果的关联:一项大型综合医疗系统许可后的观察性安全性研究
背景:雷替格拉韦成为首个获得FDA批准的整合酶抑制剂;但是,在现实世界的护理中,特别是在主要健康结果方面,记录长期风险的证据有限。目的:在综合卫生系统中评估雷替重力韦在临床实践中的安全性。方法:我们对2005年至2013年在加州凯撒医疗机构内感染hiv的成年人进行了一项队列研究。我们比较了两组在研究期间开始使用雷替重力韦的患者;一个历史队列(2005-2007年开始新的抗逆转录病毒疗法[ART])和一个同期队列(2007-2013年未开始使用雷替格拉韦)。我们使用多变量Cox比例风险回归来获得预先指定的事件健康结局的风险比(HR),并使用倾向评分来调整潜在的混杂因素。结果:人群包括8,219名hiv感染的成年人(雷替格拉韦队列N = 1,757;4,798例患者年),已知在雷替格拉韦患者中感染艾滋病毒的年数更大。雷替重力韦组增加了艾滋病定义的HR (HR 2.69 [1.53-4.71];HR 1.85[1.21-2.82])和非艾滋病定义的恶性肿瘤(HR 2.26 [1.29-3.94];HR为1.88[1.26-2.78])。与历史队列相比,我们发现全因死亡率无显著差异;与同期相比,雷替韦韦组的全因死亡率增加(HR为1.53[1.02-2.31])。与历史队列相比,雷替格拉韦对脂肪营养不良具有保护作用,但与同期相比,发病率增加。两组在肝脏、皮肤或心血管事件的发生率上没有显著差异。结论:雷替韦韦的潜在恶性肿瘤风险和死亡率升高以及残留的混杂因素值得进一步研究。我们证明了观察队列对监测许可后用药安全性的价值。
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来源期刊
HIV Clinical Trials
HIV Clinical Trials 医学-传染病学
CiteScore
1.76
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: HIV Clinical Trials is devoted exclusively to presenting information on the latest developments in HIV/AIDS clinical research. This journal enables readers to obtain the most up-to-date, innovative research from around the world.
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