Chelsea & Westminster Hospital, London, UK.
AIDS. 2011 Jan 2;25(1):65-71. doi: 10.1097/QAD.0b013e328341685b.
Two nucleoside reverse transcriptase inhibitors (NRTIs) and efavirenz (EFV) is a recommended initial regimen for HIV-1. Most EFV-related central nervous system (CNS) toxicity resolves early though symptoms may persist; we studied switching to etravirine (ETR) in these individuals.
A randomized, double-blind trial in patients with viral suppression but ongoing CNS adverse events after more than 12 weeks EFV. Patients received 2NRTI/EFV/ETR-placebo (delayed switch) or 2NRTI/ETR/EFV-placebo (immediate switch) for 12 weeks followed by 12-week open-label phase (2NRTI/ETR). Primary end-point was percentage with G2-4 CNS adverse events at 12 weeks.
Thirty-eight men; 20/18 were randomized to immediate switch/delayed switch; median CD4 was 444/498 cells/μl, respectively. Baseline CNS adverse events were similar. Nineteen immediate switch patients completed follow-up (one lost to follow-up) and 13 on delayed switch (two lost to follow-up, two withdrawn consent, one adverse event). Immediate switch G2-4 CNS adverse event: 90% at baseline, 60% at week 12 (P = 0.041). Delayed switch G2-4 CNS adverse event: 88.9% at baseline, 81.3% at week 12 (P = ns). Combined (both arms) percentage decline in G2-4 CNS adverse event after 12 weeks of ETR was significant for overall adverse events, insomnia, abnormal dreams and nervousness (P = 0.009, 0.016, 0.001, and 0.046, respectively). All participants on study maintained HIV-RNA below 50 and median week 24 CD4 was 593 and 607 cells/μl on immediate switch and delayed switch. Two participants experienced new G3-4 adverse events [delayed switch: G3 flatulence on EFV); immediate switch: G4 viral URTI on ETR (SAE)].
Switching EFV to ETR led to a significant reduction in overall G2-4 CNS adverse events, including insomnia, abnormal dreams and nervousness as individual adverse event. Lack of improvement for some events suggests other causative factors.
两种核苷类逆转录酶抑制剂（NRTIs）和依非韦伦（EFV）是 HIV-1 的推荐初始治疗方案。尽管大多数 EFV 相关的中枢神经系统（CNS）毒性会早期缓解，但症状可能会持续存在；我们研究了在这些患者中改用依曲韦林（ETR）。
一项在接受病毒抑制但在 EFV 治疗 12 周后仍有持续 CNS 不良反应的患者中进行的随机、双盲试验。患者接受了 2NRTI/EFV/ETR-安慰剂（延迟转换）或 2NRTI/ETR/EFV-安慰剂（即刻转换）治疗 12 周，随后进行 12 周的开放标签期（2NRTI/ETR）。主要终点是在 12 周时 CNS 不良反应 G2-4 的百分比。
38 名男性；20/18 名患者被随机分配至即刻转换/延迟转换；中位 CD4 分别为 444/498 个细胞/μl。基线 CNS 不良反应相似。19 名即刻转换患者完成了随访（1 名失访），13 名延迟转换患者完成了随访（2 名失访，2 名退出知情同意，1 名不良反应）。即刻转换 CNS 不良反应 G2-4：基线时为 90%，第 12 周时为 60%（P = 0.041）。延迟转换 CNS 不良反应 G2-4：基线时为 88.9%，第 12 周时为 81.3%（P = 无统计学意义）。12 周 ETR 后，总体不良反应、失眠、异常梦境和紧张的 G2-4CNS 不良反应百分比下降具有显著意义（P = 0.009、0.016、0.001 和 0.046）。所有接受研究的患者均将 HIV-RNA 维持在 50 以下，即刻转换和延迟转换的中位第 24 周 CD4 分别为 593 和 607 个细胞/μl。两名患者出现新的 G3-4 不良事件[延迟转换：EFV 时 G3 级腹胀；即刻转换：ETR 时 G4 级病毒上呼吸道感染（SAE）]。
将 EFV 转换为 ETR 可显著降低总体 G2-4CNS 不良反应，包括失眠、异常梦境和紧张，作为单独的不良反应。一些事件无改善表明存在其他致病因素。
