Department of Medicine, University of Bonn, Germany.
Clin Infect Dis. 2011 Oct;53(8):807-16. doi: 10.1093/cid/cir510.
We compared 3 years of antiretroviral therapy with raltegravir or efavirenz as part of a combination regimen in the ongoing STARTMRK study of treatment-naive patients infected with human immunodeficiency virus (HIV).
Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies/mL and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind, noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. Outcomes included viral suppression, adverse events, and changes from baseline metabolic parameters. Dual energy X-ray absorptiometry scans were obtained on a convenience sample of patients at prespecified time points to assess changes in body fat composition.
At week 156 counting noncompleters as failures, 212 (75.4%) of 281 versus 192 (68.1%) of 282 had vRNA levels <50 copies/mL in the raltegravir and efavirenz groups, respectively [Δ (95% CI) = 7.3% (-0.2, 14.7), noninferiority P < .001]. Mean changes from baseline CD4 count were 332 and 295 cells/mm³ in the raltegravir and efavirenz arms, respectively [Δ (95% CI) = 37 (4, 69)]. Consistent virologic and immunologic efficacy was maintained across prespecified demographic and baseline prognostic subgroups for both treatment groups. Fewer drug-related clinical adverse events (49% vs 80%; P < .001) occurred in raltegravir than efavirenz recipients, with discontinuations due to adverse events in 5% and 7%, respectively. Elevations in fasting lipid levels (including LDL- and HDL-cholesterol) were consistently lower in the raltegravir than efavirenz group (P < .005). Fat gain was 19% in 25 raltegravir recipients and 31% in 32 efavirenz recipients at week 156.
When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir produced durable viral suppression and immune restoration that was at least equivalent to efavirenz through 156 weeks of therapy. Both regimens were well tolerated, but raltegravir was associated with fewer drug-related clinical adverse events and smaller elevations in lipid levels. Clinical Trials Registration. NCT00369941.
我们比较了拉替拉韦或依非韦伦联合治疗方案中 3 年的抗逆转录病毒治疗，作为正在进行的初治 HIV 感染者的 STARTMRK 研究的一部分。
符合条件的 HIV-1 RNA（vRNA）水平>5000 拷贝/ml 且无基线对依非韦伦、替诺福韦或恩曲他滨耐药的患者，在一项双盲、非劣效性研究中，随机分为拉替拉韦或依非韦伦组，分别联合替诺福韦/恩曲他滨治疗。主要终点为病毒抑制、不良事件和基线代谢参数的变化。在指定的时间点，通过便利抽样的患者进行双能 X 射线吸收仪扫描，以评估体脂成分的变化。
在 156 周时，不计入未完成患者的失败率，281 例患者中有 212 例（75.4%）和 282 例患者中有 192 例（68.1%）病毒载量<50 拷贝/ml，分别为拉替拉韦和依非韦伦组（Δ（95%CI）=7.3%（-0.2，14.7），非劣效性 P<0.001）。拉替拉韦和依非韦伦组分别从基线的 CD4 计数增加 332 和 295 个细胞/mm³（Δ（95%CI）=37（4，69））。两种治疗组在所有预先指定的人口统计学和基线预后亚组中，病毒学和免疫学疗效均保持一致。拉替拉韦组的药物相关临床不良事件发生率（49%比 80%；P<0.001）低于依非韦伦组，分别有 5%和 7%的患者因不良事件而停药。空腹血脂水平（包括 LDL-和 HDL-胆固醇）升高在拉替拉韦组始终低于依非韦伦组（P<0.005）。在第 156 周时，拉替拉韦组有 25 例患者出现脂肪增加 19%，依非韦伦组有 31 例患者出现脂肪增加 31%。
在初治患者中，与替诺福韦/恩曲他滨联合应用时，拉替拉韦产生了持久的病毒抑制和免疫恢复，至少与依非韦伦在 156 周的治疗中相当。两种方案均耐受良好，但拉替拉韦相关的药物相关临床不良事件较少，血脂水平升高较小。临床试验注册。NCT00369941。
