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IF 2.8 3区医学 Q2 INFECTIOUS DISEASES

HIV Medicine Pub Date : 2025-01-24 DOI:10.1111/hiv.13761

Eva Agnes Laker Odongpiny, Melanie Nicol, Elizabeth Katana, Joseph Owori, Allan Buzibye, Kay Sedan, Mike Kesby, Matthew Holden, Noela Owarwo, David Meya, Barbara Castelnuovo, Derek J. Sloan, Christine Sekaggya

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引用次数: 0

摘要

Dolutegravir目前在撒哈拉以南非洲广泛使用，作为抗逆转录病毒治疗（ART）的首选成分。目前很少有大型研究利用常规收集的非洲艾滋病毒感染者的数据来为艾滋病毒规划提供信息。我们回顾了一个大型艾滋病病毒感染者的临床资料，以确定多替格拉韦在现实世界中的安全性和耐受性，并描述了停药的驱动因素。方法：我们对2017年2月至2020年12月期间在乌干达坎帕拉传染病研究所开始或转向以甘地利酯为基础的抗逆转录病毒治疗的艾滋病毒感染者进行了回顾性动态队列分析。不良事件（ae）的类型根据监管活动医学词典进行分类。采用Cox比例风险法确定不良事件发生率和停药率。结果：在4529例开始使用或切换使用多替格拉韦的HIV感染者中，2094例（45.9%）为女性，中位年龄为49岁（四分位数范围[IQR] 41-56）。随访8907.93人年（PY）， 1069人年（23.6%）；95%可信区间[CI] 22.4-24.8)，艾滋病毒感染者发生AE，发生率为10.43 / 1000 PY （95% CI 9.77-11.14）。神经精神、胃肠和内分泌不良反应最为常见。促使多替格拉韦停药的主要ae是高血糖(140/356；39.3%)和勃起功能障碍(19/356；5.3%)。只有1.2%（4/356）的多替替韦停药是由于神经精神不良事件。女性(校正风险比[aHR] 1.35；95% CI 1.02-1.78)和既往使用司他夫定(aHR 1.46；95% CI 1.04-2.05)是神经精神ae的主要预测因子。高血糖的危险因素包括超重(aHR 1.66；95% CI 1.11-2.47)或肥胖(aHR 1.84；95% CI 1.12-3.05)，有高血压(aHR 1.92；95% CI 1.35-2.73)，患有糖尿病(aHR 12.6；95% CI 8.34-19.1)，既往服用含有齐多夫定的抗逆转录病毒治疗(aHR 1.76；95% CI 1.19-2.59)或司他夫定(aHR 1.68；95% ci 1.15-2.44)。这些高血糖的危险因素也是多替格拉韦停药的主要原因。结论：ae在这个非洲队列中很常见，多替格拉韦停药是由高血糖和勃起功能障碍引起的。先前使用已知线粒体毒性的较早ART与神经精神ae和高血糖相关。非洲国家使用这些药物的时间较长，这可能会导致这种风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A programmatic assessment of dolutegravir adverse events and discontinuations in Uganda

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A programmatic assessment of dolutegravir adverse events and discontinuations in Uganda

Introduction

Dolutegravir is now extensively used in sub-Saharan Africa as a preferred component of antiretroviral therapy (ART). There is a paucity of large studies using routinely collected data from African people living with HIV on dolutegravir-based regimens to inform HIV programmes. We reviewed data in a large programme clinic of people living with HIV on dolutegravir to determine the real-world safety and tolerability of dolutegravir and to describe drivers of treatment discontinuation.

Methods

We carried out a retrospective dynamic cohort analysis of people living with HIV who started on or switched to dolutegravir-based ART at the Infectious Diseases Institute in Kampala, Uganda, between February 2017 and December 2020. Types of adverse events (AEs) were classified according to the Medical Dictionary for Regulatory Activities. Incident rates for AEs and treatment discontinuation were determined using Cox proportional hazard methods.

Results

Of 4529 people living with HIV started on or switched to dolutegravir, 2094 (45.9%) were female, and the median age was 49 years (interquartile range [IQR] 41–56). During 8907.93 person-years (PY) of follow-up, 1069 (23.6%; 95% confidence interval [CI] 22.4–24.8) people living with HIV had an AE, at a rate of 10.43 per 1000 PY (95% CI 9.77–11.14). Neuropsychiatric, gastrointestinal, and endocrine AEs were most common. The main AEs driving dolutegravir discontinuation were hyperglycaemia (140/356; 39.3%) and erectile dysfunction (19/356; 5.3%). Only 1.2% (4/356) of the dolutegravir discontinuations were because of neuropsychiatric AEs. Being female (adjusted hazard ratio [aHR] 1.35; 95% CI 1.02–1.78) and previous use of stavudine (aHR 1.46; 95% CI 1.04–2.05) were the main predictors of neuropsychiatric AEs. Risk factors for hyperglycaemia included being overweight (aHR 1.66; 95% CI 1.11–2.47) or obese (aHR 1.84; 95% CI 1.12–3.05), having hypertension (aHR 1.92; 95% CI 1.35–2.73), having diabetes mellitus (aHR 12.6; 95% CI 8.34–19.1), and taking previous ART containing zidovudine (aHR 1.76; 95% CI 1.19–2.59) or stavudine (aHR 1.68; 95% CI 1.15–2.44). These risk factors for hyperglycaemia were also the main drivers of dolutegravir discontinuation.

Conclusion

AEs were common in this African cohort, and dolutegravir discontinuation was driven by hyperglycaemia and erectile dysfunction. Previous use of older ART with known mitochondrial toxicity was associated with neuropsychiatric AEs and hyperglycaemia. African countries used these drugs for longer periods, and this may contribute to this risk.

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来源期刊

HIV Medicine 医学-传染病学

CiteScore

5.10

自引率

10.00%

发文量

167

审稿时长

6-12 weeks

期刊介绍： HIV Medicine aims to provide an alternative outlet for publication of international research papers in the field of HIV Medicine, embracing clinical, pharmocological, epidemiological, ethical, preclinical and in vitro studies. In addition, the journal will commission reviews and other feature articles. It will focus on evidence-based medicine as the mainstay of successful management of HIV and AIDS. The journal is specifically aimed at researchers and clinicians with responsibility for treating HIV seropositive patients.