阿巴卡韦-拉米夫定与替诺福韦-恩曲他滨用于初治HIV-1感染的治疗比较
Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy.
作者信息
Sax Paul E, Tierney Camlin, Collier Ann C, Fischl Margaret A, Mollan Katie, Peeples Lynne, Godfrey Catherine, Jahed Nasreen C, Myers Laurie, Katzenstein David, Farajallah Awny, Rooney James F, Ha Belinda, Woodward William C, Koletar Susan L, Johnson Victoria A, Geiseler P Jan, Daar Eric S
机构信息
Division of Infectious Diseases and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
出版信息
N Engl J Med. 2009 Dec 3;361(23):2230-40. doi: 10.1056/NEJMoa0906768. Epub 2009 Dec 1.
BACKGROUND
The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.
METHODS
In a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).
RESULTS
A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.
CONCLUSIONS
In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)
背景
对于1型人类免疫缺陷病毒（HIV-1）感染患者，推荐使用固定剂量组合的核苷类逆转录酶抑制剂（NRTIs）与非核苷类逆转录酶抑制剂或利托那韦增强的蛋白酶抑制剂作为初始治疗，但尚不清楚哪种NRTI组合具有更高的疗效和安全性。
方法
在一项涉及1858例符合条件患者的随机、盲法等效性研究中，我们比较了四种每日一次的抗逆转录病毒方案作为HIV-1感染的初始治疗：阿巴卡韦-拉米夫定或替诺福韦酯（DF）-恩曲他滨加依非韦伦或利托那韦增强的阿扎那韦。主要疗效终点是从随机分组到病毒学失败的时间（定义为在16周及以后、24周之前确诊的HIV-1 RNA水平≥1000拷贝/毫升，或在24周及以后≥200拷贝/毫升）。
结果
独立数据和安全监测委员会进行的预定中期审查显示，根据NRTI组合，筛查HIV-1 RNA水平≥100000拷贝/毫升的患者在病毒学疗效方面存在显著差异。在中位随访60周时，在797例筛查HIV-1 RNA水平≥100000拷贝/毫升的患者中，阿巴卡韦-拉米夫定组的病毒学失败时间显著短于替诺福韦酯-恩曲他滨组（风险比，2.33；95%置信区间，1.46至3.72；P<0.001），阿巴卡韦-拉米夫定组有57例病毒学失败（14%），而替诺福韦酯-恩曲他滨组有26例（7%）。阿巴卡韦-拉米夫定组首次出现不良事件的时间也更短（P<0.001）。在第48周时，各研究组从基线CD4细胞计数的变化无显著差异。
结论
在筛查HIV-1 RNA水平≥100000拷贝/毫升的患者中，随机分配到阿巴卡韦-拉米夫定组的患者的病毒学失败时间和首次出现不良事件的时间均显著短于分配到替诺福韦酯-恩曲他滨组的患者。（ClinicalTrials.gov编号，NCT00118898。）
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