Kerr Wesley T, Gidal Barry, Avedissian Sean N, McAnaney Cara, Wilmshurst Jo M, Eley Brian S, Eyal Sarah, Alick-Lindstrom Sasha
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Biomedical Informatics, University of Pittsburgh, PA, USA.
Epilepsy Curr. 2024 May 28;24(4):219-231. doi: 10.1177/15357597241253500. eCollection 2024 Jul-Aug.
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.
人类免疫缺陷病毒（HIV）感染的预防近来着重于使用暴露前和暴露后预防（PrEP和PEP），这两种方法在预防HIV感染方面都非常有效。自2012年上次发布关于抗癫痫药物（ASM）与抗逆转录病毒治疗（ART）联合治疗的指南以来，这两个领域都有了众多新的药物选择。从历史上看，HIV与癫痫的联合治疗可能具有挑战性，因为病毒学失败的风险增加，且由于全球药物可及性、健康的社会决定因素以及HIV和癫痫的污名化，在获得医疗保健方面存在障碍。在这篇叙述性综述中，我们描述了基于指南的PrEP和PEP治疗与ASM之间的数据驱动和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方案没有已知的相互作用。相互作用主要集中在诱导酶的ASM、丙戊酸盐和拉莫三嗪。最显著的是，诱导酶的ASM会降低含替诺福韦的PrEP方案和PEP成分（多替拉韦、拉替拉韦和利托那韦）的血清水平，这增加了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清楚。此外，PEP中的利托那韦治疗即使在治疗的4周内也可能显著降低拉莫三嗪的血清水平，这可能增加PEP期间癫痫发作突破的风险以及停用利托那韦后皮肤反应的风险。除了PK相互作用外，重叠的副作用很常见，包括骨质减少、肝毒性和其他胃肠道效应。这篇叙述性综述旨在为所有开具ASM的临床医生提供参考，以便他们能够营造一个适宜的环境，实现癫痫的成功治疗并降低高危人群中HIV感染的风险。此外，我们强调了知识空白和未满足需求的领域，这些可通过未来的研究加以解决。
