Domingo Pere, Ribera Esteban
Unitat de Malalties Infeccioses, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España.
Enferm Infecc Microbiol Clin. 2013 Jun;31 Suppl 2:20-9. doi: 10.1016/S0213-005X(13)70139-3.
Rilpivirine (RPV) is a new, second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been recently approved for use in the initial antiretroviral therapy (ART) of treatment-naïve HIV-infected patients, combined with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). The approved dose is 25mg once daily with food. RPV has been assessed in a phase IIb study (TMC278-C204) and in three phase III trials (ECHO, THRIVE and STaR). In all of them, RPV was compared with the gold standard, efavirenz (EFV); these studies enrolled a large number of patients (n=1,349 on RPV). RPV was non-inferior to EFV at 48 and 96 weeks. In all the studies and study arms, the tolerability of RPV was better than that of EFV, especially for neuropsychiatric adverse effects, rash, and lipid profile. An analysis of the combined data from the ECHO and THRIVE trials showed marked differences, depending on baseline viral load. The therapeutic efficacy of RPV was superior to that of EFV in patients with a baseline viral load ≤ 100,000 copies/mL, due to a similar virological efficacy and a better tolerability profile. However, in patients with a baseline viral load ≥ 100,000 copies/mL, virological failure was more frequent in the RPV arm, especially in patients with a viral load ≥ 500,000 copies/mL. Emerging resistance mutations to RPV were commonly detected in patients with virological failure, especially in those with a higher baseline viral load. In view of these results, the European Medications Agency and the US Food and Drug Administration have approved the use of RPV in treatment-naïve patients with a baseline viral load ≤ 100,000 copies/mL. Some treatment guidelines have already included RPV among their recommendations. The guidelines of the US Department of Health and Human Services (DHSS) and the International Antiviral Society-USA ((IAS-USA), while awaiting additional data, consider RPV-based regimens as an alternative regimen. The Gesida guidelines consider RPV to be among the preferred regimens in patients with a viral load ≤ 100,000 copies/mL. Recent data from the STaR trial, which used fixed drug combinations, have shown the non-inferiority of RPV with respect to EFV, less virological failure and less emergence of resistance mutations with RPV use, irrespective of baseline viral load. In summary, efficacy and safety data suggest that RPV plus 2 NRTI is an effective and safe initial antiretroviral regime.
利匹韦林（RPV）是一种新型的第二代非核苷类逆转录酶抑制剂（NNRTI），最近已被批准用于初治HIV感染患者的初始抗逆转录病毒治疗（ART），与两种核苷/核苷酸类逆转录酶抑制剂（NRTI）联合使用。批准剂量为每日一次，25mg，与食物同服。RPV已在一项IIb期研究（TMC278 - C204）和三项III期试验（ECHO、THRIVE和STaR）中进行了评估。在所有这些试验中，RPV均与金标准药物依非韦伦（EFV）进行了比较；这些研究纳入了大量患者（接受RPV治疗的患者n = 1349）。在48周和96周时，RPV不劣于EFV。在所有研究及研究组中，RPV的耐受性均优于EFV，尤其是在神经精神方面的不良反应、皮疹和血脂方面。对ECHO和THRIVE试验的合并数据进行分析显示，根据基线病毒载量的不同存在显著差异。在基线病毒载量≤100,000拷贝/mL的患者中，由于病毒学疗效相似且耐受性更好，RPV的治疗效果优于EFV。然而，在基线病毒载量≥100,000拷贝/mL的患者中，RPV组的病毒学失败更为常见，尤其是在病毒载量≥500,000拷贝/mL的患者中。在病毒学失败的患者中，尤其是基线病毒载量较高的患者中，普遍检测到对RPV的新出现的耐药突变。鉴于这些结果，欧洲药品管理局和美国食品药品监督管理局已批准在基线病毒载量≤100,000拷贝/mL的初治患者中使用RPV。一些治疗指南已经将RPV纳入其推荐用药中。美国卫生与公众服务部（DHSS）和美国国际抗病毒协会（IAS - USA）的指南在等待更多数据的同时，将基于RPV的治疗方案视为一种替代方案。西班牙艾滋病研究与治疗协作组（Gesida）指南认为，在病毒载量≤100,000拷贝/mL的患者中，RPV是首选治疗方案之一。来自使用固定药物组合的STaR试验的最新数据显示，无论基线病毒载量如何，RPV在疗效上不劣于EFV，病毒学失败较少，使用RPV时耐药突变的出现也较少。总之，疗效和安全性数据表明，RPV加2种NRTI是一种有效且安全的初始抗逆转录病毒治疗方案。
