Wesley T. Kerr, Barry Gidal, Sean N. Avedissian, Cara McAnaney, Jo M. Wilmshurst, Brian S. Eley, Sarah Eyal, Sasha Alick-Lindstrom
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In this narrative review, we describe the data-driven and expected bidirectional pharmacokinetic (PK) interactions between guideline-based PrEP and PEP treatment and ASM, as well as overlapping side effects. There are many ASMs with no known interaction with PrEP or PEP regimens. The interactions focus on enzyme inducing ASMs, valproate, and lamotrigine. Most prominently, enzyme inducing ASMs lower serum levels of tenofovir-containing PrEP regimens and elements of PEP (dolutegravir, raltegravir, and ritonavir), which increased risk of virologic treatment failure in people with HIV but have unclear clinical significance on the effectiveness of PrEP and PEP. In addition, ritonavir treatment in PEP may significantly lower lamotrigine serum levels even during the 4 weeks of treatment, which may increase risk for breakthrough seizures during PEP and skin reactions after discontinuation of ritonavir. 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引用次数: 0
摘要
近来,人类免疫缺陷病毒(HIV)感染的预防工作强调使用暴露前和暴露后预防疗法(PrEP 和 PEP),这两种疗法在预防 HIV 感染方面都非常有效。自上一次于 2012 年发布有关抗癫痫药物(ASM)和抗逆转录病毒疗法(ARTs)联合治疗的指南以来,这两个领域都有了许多新的药物选择。从历史上看,HIV 和癫痫发作的联合治疗可能具有挑战性,因为病毒学失败的风险会增加,而且由于全球可用性、健康的社会决定因素以及对 HIV 和癫痫发作的污名化等原因,在获得医疗保健服务方面存在障碍。在这篇叙述性综述中,我们描述了以数据为依据、基于指南的 PrEP 和 PEP 治疗与 ASM 之间预期的双向药代动力学(PK)相互作用,以及重叠的副作用。有许多 ASM 与 PrEP 或 PEP 方案之间没有已知的相互作用。相互作用主要集中在酶诱导型 ASM、丙戊酸钠和拉莫三嗪。最突出的是,酶诱导型 ASMs 会降低含替诺福韦的 PrEP 方案和 PEP 药物(多替拉韦、拉替拉韦和利托那韦)的血清水平,从而增加 HIV 感染者病毒学治疗失败的风险,但对 PrEP 和 PEP 的有效性的临床意义尚不明确。此外,PEP 中的利托那韦治疗可能会显著降低拉莫三嗪的血清水平,即使在 4 周的治疗期间也是如此,这可能会增加 PEP 期间出现突破性癫痫发作和停用利托那韦后出现皮肤反应的风险。除了 PK 相互作用外,重叠的副作用也很常见,包括骨质疏松、肝毒性和其他胃肠道反应。这篇叙述性综述旨在为所有开具 ASMs 处方的临床医生提供资源,以便他们能够创造一个良好的环境,成功治疗癫痫发作并降低高危人群感染 HIV 的风险。此外,我们还强调了知识差距和尚未满足需求的领域,这些都可以通过未来的研究加以解决。
Pre- and Post-Exposure Prophylaxis for HIV in Patients Taking Anti-Seizure Medications
The prevention of human immunodeficiency virus (HIV) infection has recently emphasized the use of pre- and post-exposure prophylaxis (PrEP and PEP), both of which were highly effective in prevention of HIV infection. Since the last published guidance regarding the cotreatment of people with anti-seizure medications (ASM) and antiretroviral treatments (ARTs) in 2012, both fields have numerous new medication options. Historically, cotreatment of HIV and seizures could be challenging with increased risk of virologic failure and barriers in access to health care due to global availability, social determinants of health, and stigma of both HIV and seizures. In this narrative review, we describe the data-driven and expected bidirectional pharmacokinetic (PK) interactions between guideline-based PrEP and PEP treatment and ASM, as well as overlapping side effects. There are many ASMs with no known interaction with PrEP or PEP regimens. The interactions focus on enzyme inducing ASMs, valproate, and lamotrigine. Most prominently, enzyme inducing ASMs lower serum levels of tenofovir-containing PrEP regimens and elements of PEP (dolutegravir, raltegravir, and ritonavir), which increased risk of virologic treatment failure in people with HIV but have unclear clinical significance on the effectiveness of PrEP and PEP. In addition, ritonavir treatment in PEP may significantly lower lamotrigine serum levels even during the 4 weeks of treatment, which may increase risk for breakthrough seizures during PEP and skin reactions after discontinuation of ritonavir. In addition to PK interactions, overlapping side effects are common including osteopenia, hepatic toxicity, and other gastrointestinal effects. This narrative review aims to be a resource for all clinicians prescribing ASMs so that they can create a welcoming environment to enable successful treatment of seizures and reduce the risk of HIV infection in people at risk. In addition, we highlight knowledge gaps and areas of unmet need that can be addressed with future studies.
期刊介绍:
Epilepsy Currents is an open access, bi-monthly current-awareness journal providing reviews, commentaries and abstracts from the world’s literature on the research and treatment of epilepsy. Epilepsy Currents surveys and comments on all important research and developments in a format that is easy to read and reference. Each issue is divided into two main sections: Basic Science and Clinical Science. An outstanding Editorial Board reviews the literature and assigns topics and articles to world experts for comment. In addition, the Editors commission authoritative review articles on important subjects.