Formulation-Specific Safety Issues of HIV Pre-exposure Prophylaxis Drugs: A Disproportionality Analysis of the FAERS Database.

IF 3.1 3区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical Drug Investigation Pub Date : 2026-10-10 DOI:10.1007/s40261-026-01602-7

Davide Rozza, Elisabetta Poluzzi, Ippazio Cosimo Antonazzo, Angela Boccia, Marco Paccini, Fortuna Gallucci, Domenico Ponticelli, Giulio Geraci, Fernando Agüero, Giampiero Mazzaglia, Lorenzo Giovanni Mantovani, Emanuel Raschi, Pietro Ferrara

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引用次数: 0

Abstract

Background and objective: As human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) use expands, real-world post-marketing safety evidence remains limited, particularly regarding potential formulation-specific adverse-event patterns across oral and long-acting agents. We aimed to characterise the post-marketing safety profiles of FDA-approved PrEP drugs using the FDA Adverse Event Reporting System (FAERS).

Methods: We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) data from 2012 to 2024. Individual Case Safety Reports (ICSRs) listing emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), emtricitabine/tenofovir alafenamide (FTC/TAF) or cabotegravir (CAB) as suspected PrEP drugs were included. Two comparator groups were used: all non-PrEP ICSRs and ICSRs involving non-PrEP HIV drugs. Disproportionality was evaluated at the MedDRA high-level term (HLT) level using reporting odds ratios and 95% confidence intervals (CIs), identifying signals of disproportionate reporting (SDRs) with a lower bound of the 95%CIs > 1. Sensitivity analyses explored sex, reporter type, and indication.

Results: We identified 3201 PrEP-related ICSRs (FTC/TDF: 2688; FTC/TAF: 463; CAB: 50), predominantly involving young adult males. FTC/TDF exhibited a broad pattern of SDRs-including renal/metabolic abnormalities, muscular signals, mucosal disorders and some previously under-characterised signals-many of which attenuated when using HIV-treated comparators. FTC/TAF showed a narrower, highly consistent pattern dominated by hepatobiliary and metabolic monitoring procedures, renal function evaluations and neurosensory disturbances. CAB showed specific, reproducible signals for injection-site, dermatologic and procedure-related events.

Conclusions: PrEP agents display distinct, formulation-specific and reproducible safety patterns in FAERS. Comparator choice substantially influences the detection and interpretation of SDRs and can help distinguish reproducible formulation-related reporting patterns from findings that may be driven by the clinical and reporting context. These insights highlight priority areas for future research.

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HIV暴露前预防药物的配方特异性安全性问题：FAERS数据库的歧化分析。

背景和目的：随着人类免疫缺陷病毒（HIV）暴露前预防（PrEP）使用的扩大，现实世界的上市后安全性证据仍然有限，特别是关于口服和长效药物的潜在配方特异性不良事件模式。我们的目的是利用FDA不良事件报告系统（FAERS）来描述FDA批准的PrEP药物的上市后安全性概况。方法：使用2012年至2024年FDA不良事件报告系统（FAERS）数据进行歧化分析。纳入了将恩曲他滨/富马酸替诺福韦二吡酯（FTC/TDF）、恩曲他滨/替诺福韦阿拉胺（FTC/TAF）或卡波特韦（CAB）列为疑似PrEP药物的个案安全报告（ICSRs）。使用两个比较组：所有非prep icsr和涉及非prep HIV药物的icsr。在MedDRA高级别术语（HLT）水平上，使用报告比值比和95%置信区间（ci）来评估不相称性，以95% ci的下限识别不相称报告（sdr）的信号[1]。敏感性分析探讨了性别、报告者类型和适应症。结果：我们确定了3201例与prep相关的icsr (FTC/TDF: 2688; FTC/TAF: 463; CAB: 50)，主要涉及年轻成年男性。FTC/TDF表现出广泛的sdr模式，包括肾脏/代谢异常、肌肉信号、粘膜紊乱和一些以前未被描述的信号，其中许多在使用hiv治疗的比较物时减弱。FTC/TAF表现出狭窄的、高度一致的模式，主要是肝胆和代谢监测程序、肾功能评估和神经感觉障碍。CAB对注射部位、皮肤和手术相关事件显示出特异性、可重复的信号。结论：PrEP药物在FAERS中显示出独特的、配方特异性的和可重复的安全模式。比较国的选择在很大程度上影响特别提款权的检测和解释，并有助于区分可重复的配方相关报告模式与可能由临床和报告环境驱动的发现。这些见解突出了未来研究的重点领域。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.