Rey D, Hoen B, Chavanet P, Schmitt M P, Hoizey G, Meyer P, Peytavin G, Spire B, Allavena C, Diemer M, May T, Schmit J L, Duong M, Calvez V, Lang J M
COREVIH, Hôpitaux Universitaires, Strasbourg, France.
J Antimicrob Chemother. 2009 Feb;63(2):380-8. doi: 10.1093/jac/dkn471. Epub 2008 Nov 25.
The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial.
Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm(3). We planned to enroll 250 patients.
As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months.
In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.
一种非核苷类逆转录酶抑制剂（NNRTI）与两种核苷类逆转录酶抑制剂联合使用是一种经过验证的一线抗逆转录病毒（ARV）疗法。拉米夫定、替诺福韦酯和奈韦拉平每日一次的联合用药尚未在临床试验中进行评估。
一项随机、开放标签、多中心、非劣效性试验，比较每日一次的拉米夫定、替诺福韦酯和奈韦拉平（第2组）与每日两次的齐多夫定/拉米夫定和奈韦拉平（第1组）在CD4细胞计数<350/mm³的初治HIV-1感染患者中的疗效。我们计划招募250名患者。
截至2006年5月，已招募71名患者（第1组35名，第2组36名），并进行了一次非计划的中期分析。两组在基线时具有可比性：第1组和第2组的CD4细胞计数中位数分别为195和191/mm³，血浆病毒载量中位数分别为4.9 log₁₀和5.01 log₁₀。观察到8例早期无反应（22.2%），均在第2组，同时发生2例后期病毒反弹。第2组9例失败患者的耐药基因型显示有M184V/I突变（n = 3）、K65R突变（n = 6），所有病例均有一个或多个NNRTI耐药突变。在基线时，第2组中9例失败患者的血浆病毒载量中位数（5.4 log₁₀）高于其他第2组患者（4.7 log₁₀，P = 0.002），CD4细胞计数中位数（110/mm³）低于其他第2组患者（223/mm³，P = 0.004）。两组之间以及第2组中病毒完全抑制的患者与失败患者之间奈韦拉平谷浓度无差异。由于招募缓慢以及这些结果，指导委员会决定在12个月时停止试验。
在初治HIV-1感染患者中，每日一次的拉米夫定、替诺福韦酯和奈韦拉平方案导致早期病毒学失败率较高。失败原因尚不清楚。
