Divisions of Clinical Pharmacology and Infectious Diseases, Department of Medicine and Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine.
Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Curr Opin HIV AIDS. 2022 Jul 1;17(4):192-198. doi: 10.1097/COH.0000000000000735.
The main reason for the failure of oral preexposure prophylaxis (PrEP) regimens for HIV is poor adherence. Intramuscular cabotegravir was recently approved for PrEP, and a number of other long-acting antiretroviral formulations and products are currently in clinical development. This includes subcutaneous and intravenous injections, implants, and microarray (microneedle) patches, as well as extended duration oral drugs. The success and future uptake of these products will depend on a variety of factors.
Long-acting delivery of antiretroviral agents for PrEP confers significant advantages over short-acting oral delivery. This is exemplified by the superior efficacy of intramuscular cabotegravir given every eight weeks as compared to daily oral co-formulated tenofovir disoproxil fumarate and emtricitabine. There is also evidence for PrEP efficacy for a broadly neutralizing monoclonal antibody given intravenously every eight weeks. One of the leading candidates for long-acting PrEP, islatravir, was being studied as a monthly oral drug or a nonerodable subcutaneous implant inserted for up to 12 months. However, clinical studies of this agent were put on hold in late 2021 because of unanticipated lymphopenia.
Long-acting antiretroviral products have substantial promise for PrEP and have particular advantages over daily oral drugs based mainly on improved adherence. However, there are barriers to further uptake that include the need for more intensive interaction with systems of healthcare delivery, greater expense and complexity of implementation, and unexpected long-term toxicities.
口服暴露前预防 (PrEP) 方案失败的主要原因是依从性差。肌肉注射卡替拉韦最近被批准用于 PrEP，许多其他长效抗逆转录病毒制剂和产品目前正在临床开发中。这包括皮下和静脉注射、植入物和微阵列（微针）贴片，以及延长口服药物的作用时间。这些产品的成功和未来应用将取决于多种因素。
长效抗逆转录病毒药物的输送为 PrEP 提供了优于短期口服输送的显著优势。肌肉注射卡替拉韦每 8 周给药一次，优于每日口服联合制剂替诺福韦二吡呋酯和恩曲他滨，这就是一个很好的例子。每 8 周静脉注射一种广泛中和单克隆抗体也有预防效果的证据。长效 PrEP 的主要候选药物之一伊拉特拉韦，正在作为每月口服药物或长达 12 个月的不可吸收皮下植入物进行研究。然而，由于意外的淋巴细胞减少症，该药物的临床研究于 2021 年底暂停。
长效抗逆转录病毒产品在 PrEP 方面具有很大的潜力，并且与主要基于改善依从性的每日口服药物相比具有特别的优势。然而，进一步推广还存在障碍，包括需要与医疗保健提供系统进行更深入的互动、更高的费用和实施的复杂性以及意外的长期毒性。
