Current status and prospects of HIV treatment
Current status and prospects of HIV treatment
复制标题
DOI：
10.1016/j.coviro.2016.03.004
复制
发表时间：
2016-06-01
影响因子：
5.9
通讯作者：
Fordyce, Marshall
中科院分区：
文献类型：
--
作者：
Cihlar, Tomas;Fordyce, Marshall
目前的抗病毒治疗可以减少艾滋病毒相关的发病率，延长生存时间，防止艾滋病毒传播。持久的病毒学抑制需要联合抗逆转录病毒疗法(CART)，最好包含来自两个或更多类别的三种活性药物。方案的选择基于病毒学疗效、潜在的不良反应、药物负担和剂量频率、药物-药物相互作用潜力、耐药性测试结果、共病条件、社会地位和成本。随着病毒学抑制时间的延长、临床结果的改善和生存期的延长，患者将暴露在抗逆转录病毒药物中数十年。因此，最大限度地提高CART的安全性和耐受性是当务之急。个别患者出现耐药性和/或缺乏耐受性，需要有一系列的治疗选择。新药的开发侧重于提高现有药物类别中的安全性(例如替诺福韦丙氨酰胺)和/或耐药性(例如多拉韦林)，改善依从性的联合疗法(例如单一片剂方案)，新的作用机制(例如附着抑制剂、成熟抑制剂、广谱中和抗体)，以及以较少的剂量简化治疗(例如长效注射剂)。在CART创新的同时，专注于针对持久性艾滋病毒蓄积者的药物的研究和开发工作可能会导致长期的无药物缓解和艾滋病毒治愈。
Current antiviral treatments can reduce HIV-associated morbidity, prolong survival, and prevent HIV transmission. Combination antiretroviral therapy (cART) containing preferably three active drugs from two or more classes is required for durable virologic suppression. Regimen selection is based on virologic efficacy, potential for adverse effects, pill burden and dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, social status, and cost. With prolonged virologic suppression, improved clinical outcomes, and longer survival, patients will be exposed to antiretroviral agents for decades. Therefore, maximizing the safety and tolerability of cART is a high priority. Emergence of resistance and/or lack of tolerability in individual patients require availability of a range of treatment options. Development of new drugs is focused on improving safety (e.g. tenofovir alafenamide) and/or resistance profile (e.g. doravirine) within the existing drug classes, combination therapies with improved adherence (e.g. single-tablet regimens), novel mechanisms of action (e.g. attachment inhibitors, maturation inhibitors, broadly neutralizing antibodies), and treatment simplification with infrequent dosing.(e.g. long-acting injectables). In parallel with cART innovations, research and development efforts focused on agents that target persistent HIV reservoirs may lead to prolonged drug-free remission and HIV cure.