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个性化预防:HIV预防药物治疗的进展

Personalizing prevention: Advances in pharmacotherapy for HIV prevention.

作者信息

Brizzi Marisa, Sherman Elizabeth M, Green Sarah B, Nowicki Diana N, Drwiega Emily N, Nicol Melanie R, Chastain Daniel B, Sahloff Eric G, Truong William R, Cluck David, Badowski Melissa E, Michienzi Sarah M, Durham Spencer H

机构信息

Department of Pharmacy, University of Cincinnati (UC) Health, Ohio, Cincinnati, USA.

Department of Pharmacy Practice, Nova Southeastern University College of Pharmacy, Florida, Ft. Lauderdale, USA.

出版信息

Pharmacotherapy. 2023 Apr;43(4):305-320. doi: 10.1002/phar.2796. Epub 2023 Apr 1.

Abstract

The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence.

摘要

艾滋病毒疫情继续给医疗系统带来重大负担。尽管每年新感染病例的发生率在下降,但健康差距依然存在,大多数新感染病例仍集中在不同的种族、民族和少数群体中。暴露前预防(PrEP),即让有感染艾滋病毒高风险的人服用慢性药物以预防感染该病毒,是预防新的艾滋病毒感染的关键。本文的目的是回顾PrEP的药物治疗方法,并研究它们在不同患者群体中个性化PrEP方面的作用。此外,还对目前正在研发的用于PrEP的新药物,以及治疗即预防(TasP)和暴露后预防(PEP)进行了综述。目前有四种药物可用于PrEP:复方恩曲他滨/替诺福韦酯(FTC/TDF)或恩曲他滨/替诺福韦艾拉酚胺(FTC/TAF)的口服制剂;长效注射用卡博特韦(CAB-LA);以及阴道环达匹韦林(DPV-VR)。由于缺乏研究,目前FTC/TAF未被批准用于通过阴道性行为感染艾滋病毒风险的人群,但相关试验正在进行中。DPV-VR在津巴布韦和南非有售,并已得到世界卫生组织的认可,但目前在美国尚未上市。还有几种药物也正在研发中用于PrEP:新型长效注射用lenacapavir,这是一种一流的衣壳抑制剂,对任何现有的艾滋病毒药物类别均无交叉耐药性;皮下植入物islatravir,这是一种一流的易位抑制剂;以及VRC01,一种广泛中和抗体(bnAb),已在概念验证研究中进行了评估,可能会促使研发出更有效的bnAb。总体而言,PrEP在预防高危人群感染艾滋病毒方面非常有效。在不同患者群体中确定最佳的PrEP方案很复杂,必须考虑患者的具体因素以及药物成本和可及性等因素。最后,医疗服务提供者应考虑患者在预防方面的个人偏好,以提高可及性、护理依从性和留存率。

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