Université Pierre et Marie Curie, Paris VI and Hôpital Pitié-Salpêtrière, Paris, France.
AIDS. 2009 Nov 13;23(17):2289-300. doi: 10.1097/QAD.0b013e3283316a5e.
To evaluate the efficacy, safety and virologic resistance profile of etravirine (TMC125), a next-generation nonnucleoside reverse transcriptase inhibitor, over 48 weeks in treatment-experienced adults infected with HIV-1 strains resistant to a nonnucleoside reverse transcriptase inhibitor and other antiretrovirals.
DUET-1 (NCT00254046) and DUET-2 (NCT00255099) are two identically designed, randomized, double-blind phase III trials.
Patients received twice-daily etravirine 200 mg or placebo, each plus a background regimen of darunavir/ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors and optional enfuvirtide. Eligible patients had documented nonnucleoside reverse transcriptase inhibitor resistance, at least three primary protease inhibitor mutations at screening and were on a stable but virologically failing regimen for at least 8 weeks, with plasma viral load more than 5000 copies/ml. Pooled 48-week data from the two trials are presented.
Patients (1203) were randomized and treated (n = 599, etravirine; n = 604, placebo). Significantly more patients in the etravirine than in the placebo group achieved viral load less than 50 copies/ml at week 48 (61 vs. 40%, respectively; P < 0.0001). Significantly fewer patients in the etravirine group experienced at least one confirmed or probable AIDS-defining illness/death (6 vs. 10%; P = 0.0408). Safety and tolerability in the etravirine group was comparable to the placebo group. Rash was the only adverse event to occur at a significantly higher incidence in the etravirine group (19 vs. 11%, respectively, P < 0.0001), occurring primarily in the second week of treatment.
At 48 weeks, treatment-experienced patients receiving etravirine plus background regimen had statistically superior and durable virologic responses (viral load less than 50 copies/ml) than those receiving placebo plus background regimen, with comparable tolerability and no new safety signals reported since week 24.
评估下一代非核苷类逆转录酶抑制剂依曲韦林（TMC125）在治疗曾接受过非核苷类逆转录酶抑制剂和其他抗逆转录病毒药物治疗的 HIV-1 株耐药的成人患者中的疗效、安全性和病毒学耐药情况，疗程为 48 周。
DUET-1（NCT00254046）和 DUET-2（NCT00255099）是两项设计相同、随机、双盲的 III 期临床试验。
患者每日两次接受依曲韦林 200mg 或安慰剂治疗，两者均联合达芦那韦/利托那韦、研究者选择的核苷/核苷酸逆转录酶抑制剂以及可选的恩夫韦肽。符合条件的患者有记录的非核苷类逆转录酶抑制剂耐药性，筛选时至少有三种主要蛋白酶抑制剂突变，且在稳定但病毒学上失败的治疗方案中至少 8 周，血浆病毒载量大于 5000 拷贝/ml。现将两项试验的 48 周汇总数据进行报告。
1203 例患者被随机分组并接受治疗（n = 599，依曲韦林；n = 604，安慰剂）。依曲韦林组在第 48 周时病毒载量小于 50 拷贝/ml 的患者比例显著高于安慰剂组（分别为 61%和 40%；P<0.0001）。依曲韦林组发生至少一次确认或可能的 AIDS 定义性疾病/死亡的患者比例显著低于安慰剂组（分别为 6%和 10%；P=0.0408）。依曲韦林组的安全性和耐受性与安慰剂组相当。皮疹是唯一在依曲韦林组发生率显著较高的不良事件（分别为 19%和 11%；P<0.0001），主要发生在治疗的第二周。
在第 48 周时，接受依曲韦林联合背景治疗的治疗经验丰富的患者与接受安慰剂联合背景治疗的患者相比，具有统计学上更优且更持久的病毒学应答（病毒载量小于 50 拷贝/ml），且耐受性相当，自第 24 周以来没有报告新的安全性信号。
