The future of long-acting agents for preexposure prophylaxis.
The future of long-acting agents for preexposure prophylaxis.
复制标题
用于暴露前预防的长效剂的未来。
DOI：
10.1097/coh.0000000000000735
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发表时间：
2022-07-01
影响因子：
4.1
通讯作者：
Flexner, Charles
中科院分区：
文献类型：
--
作者：
Flexner, Charles
关键词：
口服暴露前预防（PrEP）方案失败的主要原因是依从性差。肌内注射cabotegravir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，植入和微阵列（微针）贴片，以及持续时间较长的口服药物。这些产品的成功和未来的采用将取决于各种因素。用于PrEP的抗逆转录病毒药物的长效递送比短效口服递送具有显著优势。这通过与每日口服共配制的富马酸替诺福韦二异丙酯和恩曲他滨相比，每八周给予肌内卡替拉韦的上级功效来例证。也有证据表明，每八周静脉注射一次广泛中和的单克隆抗体对PrEP有效。作为长效PrEP的主要候选药物之一，islatravir正在被研究为每月口服药物或插入长达12个月的非侵蚀性皮下植入物。然而，该药物的临床研究于二零二一年底因意外的淋巴细胞减少症而暂停。长效抗逆转录病毒产品对PrEP有很大的希望，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，进一步采用存在障碍，包括需要与卫生保健提供系统进行更密集的互动，实施费用更高，实施复杂性更大，以及意外的长期毒性。
The main reason for failure of oral pre-exposure 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 non-erodable 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 health care delivery, greater expense and complexity of implementation, and unexpected long-term toxicities.