Department of Clinical Research, Tuberculosis Research Centre, Indian Council of Medical Research, Chennai, India.
Clin Infect Dis. 2011 Oct;53(7):716-24. doi: 10.1093/cid/cir447.
Nevirapine (NVP) can be safely and effectively administered once-daily but has not been assessed in human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB). We studied the safety and efficacy of once-daily NVP, compared with efavirenz (EFV; standard therapy); both drugs were administered in combination with 2 nucleoside reverse-transcriptase inhibitors.
An open-label, noninferiority, randomized controlled clinical trial was conducted at 3 sites in southern India. HIV-infected patients with TB were treated with a standard short-course anti-TB regimen (2EHRZ(3)/4RH(3); [2 months of Ethambutol, Isoniazid, Rifampicin, Pyrazinamide / 4 months of Isoniazid and Rifampicin] thrice weekly) and randomized to receive once-daily EFV at a dose of 600 mg or NVP at a dose of 400 mg (after 14 days of 200 mg administered once daily) with didanosine 250/400 mg and lamivudine 300 mg after 2 months. Sputum smears and mycobacterial cultures were performed every month. CD4+ cell count, viral load, and liver function test results were monitored periodically. Primary outcome was a composite of death, virological failure, default, or serious adverse event (SAE) at 24 weeks. Both intent-to-treat and per protocol analyses were done, and planned interim analyses were performed.
A total of 116 patients (75% [87 patients] of whom had pulmonary TB), with a mean age of 36 years, a median CD4+ cell count of 84 cells/mm(3), and a median viral load of 310 000 copies/mL, were randomized. At 24 weeks, 50 of 59 patients in the EFV group and 37 of 57 patients in the NVP group had virological suppression (P = .024). There were no deaths, 1 SAE, and 5 treatment failures in the EFV arm, compared with 5 deaths, 2 SAEs, and 10 treatment failures in the NVP arm. The trial was halted by the data and safety monitoring board at the second interim analysis. Favorable TB treatment outcomes were observed in 93% of the patients in the EFV arm and 84% of the patients in the NVP arm (P = .058).
Compared with a regimen of didanosine, lamivudine, and EFV, a regimen of once-daily didanosine, lamivudine, and NVP was inferior and was associated with more frequent virologic failure and death. Clinical Trials Registration. NCT00332306.
奈韦拉平（NVP）可以安全有效地每日服用一次，但尚未在患有结核病（TB）的人类免疫缺陷病毒（HIV）感染者中进行评估。我们研究了每日一次的 NVP 的安全性和疗效，与依非韦伦（EFV；标准疗法）进行比较；两种药物均与 2 种核苷逆转录酶抑制剂联合使用。
在印度南部的 3 个地点进行了一项开放性、非劣效性、随机对照临床试验。患有结核病的 HIV 感染者接受标准短程抗结核治疗方案（2EHRZ（3）/4RH（3）；[2 个月的乙胺丁醇、异烟肼、利福平、吡嗪酰胺/4 个月的异烟肼和利福平]每周 3 次），并随机接受每日一次 EFV 剂量为 600mg 或 NVP 剂量为 400mg（在每日一次服用 14 天后给予 200mg），与双脱氧肌苷 250/400mg 和拉米夫定 300mg 合用。每月进行痰涂片和分枝杆菌培养。定期监测 CD4+细胞计数、病毒载量和肝功能检查结果。主要终点是 24 周时死亡、病毒学失败、失访或严重不良事件（SAE）的复合事件。进行了意向治疗和方案分析，并且进行了计划的中期分析。
共有 116 名患者（其中 75%[87 名患者]患有肺结核），平均年龄 36 岁，中位 CD4+细胞计数为 84 个/立方毫米，中位病毒载量为 310000 拷贝/mL，进行了随机分组。在 24 周时，EFV 组的 59 名患者中有 50 名和 NVP 组的 57 名患者中有 37 名达到病毒学抑制（P=0.024）。EFV 组有 1 例 SAE 和 5 例治疗失败，而 NVP 组有 5 例死亡、2 例 SAE 和 10 例治疗失败。数据和安全监测委员会在第二次中期分析时中止了试验。EFV 组 93%的患者和 NVP 组 84%的患者获得了有利的结核病治疗结果（P=0.058）。
与包含双脱氧肌苷、拉米夫定和依非韦伦的方案相比，包含每日一次双脱氧肌苷、拉米夫定和 NVP 的方案效果较差，且与更频繁的病毒学失败和死亡相关。临床试验注册。NCT00332306。
