David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
UCLA Center for Clinical AIDS Research & Education (CARE), Division of Infectious Diseases, University of California, Los Angeles, CA, USA.
Curr HIV/AIDS Rep. 2020 Apr;17(2):118-124. doi: 10.1007/s11904-020-00486-2.
Combination antiretroviral therapy (cART) has had dramatic effects on morbidity and mortality for persons living with HIV (PLWH). Despite significant progress in treatment efficacy, tolerability, and reducing pill burden, new agents are needed to address issues of resistance, drug-drug interactions, end organ disease, and adherence. This review covers novel ART agents recently approved or in development.
Capsid inhibitors (CAI) demonstrate high potency and potential for extended-duration dosing in pre-clinical trials. While previous maturation inhibitors (MI) were hampered by issues of drug resistance, a recent phase IIa trial for a second-generation MI demonstrated promising antiviral activity. A phase I trial to evaluate a transdermal implant of islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), maintained concentrations above the target pharmacokinetic threshold at 12 weeks. The attachment inhibitor fostemsavir is available in the USA for compassionate use in multi-drug-resistant (MDR) HIV. New antiretroviral agents show promise for both extended-duration dosing and MDR HIV.
联合抗逆转录病毒疗法（cART）显著降低了艾滋病毒感染者（PLWH）的发病率和死亡率。尽管在治疗效果、耐受性和减少药物负担方面取得了重大进展，但仍需要新的药物来解决耐药性、药物相互作用、终末器官疾病和依从性等问题。本文综述了最近批准或正在开发的新型抗逆转录病毒药物。
衣壳抑制剂（CAI）在临床前试验中表现出高活性和延长给药间隔的潜力。虽然以前的成熟抑制剂（MI）因耐药性问题而受阻，但最近一项第二代 MI 的 IIa 期试验显示出有希望的抗病毒活性。一项评估伊拉替拉韦（一种核苷逆转录酶易位抑制剂（NRTTI））透皮植入物的 I 期试验在 12 周时维持了高于目标药代动力学阈值的浓度。附着抑制剂福替沙韦在美已获准用于多药耐药（MDR）HIV 的同情用药。新型抗逆转录病毒药物在延长给药间隔和治疗 MDR HIV 方面均显示出良好的前景。
