Duvivier Claudine, Ghosn Jade, Assoumou Lambert, Soulié Cathia, Peytavin Gilles, Calvez Vincent, Génin Michèle Algarté, Molina Jean-Michel, Bouchaud Olivier, Katlama Christine, Costagliola Dominique
AP-HP, Groupe hospitalier Pitié-Salpétrière, Service de Maladies Infectieuses et Tropicales, Paris F-75013, France.
J Antimicrob Chemother. 2008 Oct;62(4):797-808. doi: 10.1093/jac/dkn278. Epub 2008 Jul 18.
The aim of this study was to evaluate the impact on body fat of nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens compared with NRTI-containing therapy in HIV-1-infected antiretroviral (ARV)-naive patients.
A randomized, multicentre, open-label trial in ARV-naive patients. Subjects were randomized (2:1:1) to receive: (i) an NRTI-sparing regimen consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus a boosted protease inhibitor (PI/r); or (ii) an NRTI-containing regimen of (a) a PI/r plus two NRTIs or (b) an NNRTI plus two NRTIs. The primary endpoint was the change in subcutaneous limb fat measured by dual-energy X-ray absorptiometry at week (W) 96. Secondary endpoints included the proportion of patients with treatment failure, plasma HIV-RNA (pVL) <50 copies/mL and safety.
One hundred and seventeen patients were enrolled between November 2003 and May 2004: 26% female; 42% from sub-Saharan Africa; median plasma HIV-RNA (pVL) 5.1 log(10) copies/mL; median CD4 count 207 cells/mm(3). A planned interim analysis demonstrated significantly lower treatment and virological responses with the NRTI-sparing strategy, resulting in premature study termination on 19 July 2005. The proportion of patients who remained on their assigned treatment strategy and had pVL <50 copies/mL on the NRTI-sparing regimen was 60.0%, compared with 82.5% on the NRTI-containing regimen at W24 (P = 0.009) and 66.7% and 82.5%, respectively, at W48 (P = 0.059). Treatment failure was associated with the NRTI-sparing strategy in patients with suboptimal adherence and with being from sub-Saharan Africa. No differences in fat distribution were noted.
An initial NRTI-sparing regimen is less successful and virologically less potent than standard NRTI-containing regimen and should not therefore be used as the first line of treatment.
本研究旨在评估在初治的HIV-1感染抗逆转录病毒（ARV）患者中，与含核苷类逆转录酶抑制剂（NRTI）治疗相比，不含NRTI方案对体脂的影响。
一项针对初治患者的随机、多中心、开放标签试验。受试者按2:1:1随机分组接受：（i）一种不含NRTI的方案，由一种非核苷类逆转录酶抑制剂（NNRTI）加一种增效蛋白酶抑制剂（PI/r）组成；或（ii）一种含NRTI的方案，即（a）一种PI/r加两种NRTI，或（b）一种NNRTI加两种NRTI。主要终点是第96周时通过双能X线吸收法测量的四肢皮下脂肪变化。次要终点包括治疗失败患者的比例、血浆HIV-RNA（pVL）<50拷贝/mL以及安全性。
2003年11月至2004年5月期间共纳入117例患者：女性占26%；42%来自撒哈拉以南非洲；血浆HIV-RNA（pVL）中位数为5.1 log(10)拷贝/mL；CD4细胞计数中位数为207个/mm³。一项计划中的中期分析显示，不含NRTI策略的治疗和病毒学反应显著较低，导致研究于2005年7月19日提前终止。在第24周时，采用不含NRTI方案且维持原分配治疗策略且pVL<50拷贝/mL的患者比例为60.0%，而含NRTI方案组为82.5%（P = 0.009）；在第48周时，相应比例分别为66.7%和82.5%（P = 0.059）。治疗失败与依从性欠佳的患者以及来自撒哈拉以南非洲的患者采用不含NRTI策略有关。未观察到脂肪分布有差异。
初始不含NRTI方案不如标准含NRTI方案成功，病毒学效果也较差，因此不应作为一线治疗方案。
