a Internal Medicine Department , Puerta de Hierro University Hospital , Majadahonda , Spain.
b Laboratory of Internal Medicine , Puerta de Hierro Research Institute , Majadahonda , Spain.
Expert Rev Clin Pharmacol. 2018 May;11(5):507-517. doi: 10.1080/17512433.2018.1453805. Epub 2018 Mar 29.
Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.
目前的抗逆转录病毒疗法能够在大多数接受治疗的患者中实现并维持 HIV 复制的最大抑制。因此,HIV 感染者的预期寿命显著提高,现在与 HIV 阴性人群相似。然而,口服抗逆转录病毒药物必须每天服用且无限期服用,以避免 HIV 复制的恢复和耐药性的选择。不幸的是,药物依从性往往并不理想,而且随着时间的推移往往会下降。
新的药物、制剂和输送系统正在被开发用于延长抗逆转录病毒药物的释放。此时,肌肉注射卡替拉韦和利匹韦林、阴道用达泊西汀环和替诺福韦艾拉酚胺皮下植入剂是处于更先进临床开发阶段的产品。对它们的药代动力学/药效学和安全性/疗效进行了回顾。
在缺乏针对 HIV 感染者的根治性疗法和针对有风险人群的保护性疫苗的情况下,长期抗逆转录病毒疗法是预防患者疾病进展和阻止传播的最佳方法,无论是作为 HIV 携带者的“治疗即预防”还是未感染者的“暴露前预防”。在所有这些情况下,长效抗逆转录病毒药物的出现将扩大克服药物依从性不佳的挑战的选择,并减轻 HIV 感染的负担。