Hôpital Saint Louis and University of Paris Diderot, Paris, France.
Lancet Infect Dis. 2012 Jan;12(1):27-35. doi: 10.1016/S1473-3099(11)70249-3. Epub 2011 Oct 18.
Elvitegravir is a once daily inhibitor of HIV-1 integrase boosted by ritonavir. We aimed to compare the efficacy and safety of elvitegravir with raltegravir, another HIV-1 integrase inhibitor, in patients in whom previous antiretroviral treatment failed.
We conducted a randomised, double-blind, double-dummy, phase 3 study at 234 sites in 13 countries. Eligible patients had plasma HIV RNA of 1000 copies per mL or greater, any CD4 cell count, and resistance to or 6 months' experience with at least two classes of antiretroviral drugs. They received an open-label background regimen of a fully active, ritonavir-boosted protease inhibitor and a second agent. We randomly allocated patients (1:1) by computer with a block size of four to receive either elvitegravir 150 mg once daily (n=361; 85 mg dose if given with atazanavir, or lopinavir with ritonavir) or raltegravir 400 mg twice daily (n=363). Placebo tablets were given to mask the difference in daily dosing. The primary endpoint was achievement and maintenance of virological response (HIV RNA <50 copies per mL) through week 48. Non-inferiority was prespecified with a margin of 10%. We did a modified intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00708162.
Ten patients allocated elvitegravir and 12 assigned raltegravir were excluded from the analysis (either for protocol violations or because they did not receive treatment). 207 (59%) of 351 patients allocated elvitegravir achieved virological response compared with 203 (58%) of 351 assigned raltegravir (treatment difference 1·1%, 95% CI -6·0 to 8·2), meeting the criterion for non-inferiority (p=0·001). Three patients allocated elvitegravir had serious adverse events related to study drugs compared with seven assigned raltegravir; two and eight patients died, respectively. More individuals assigned elvitegravir reported diarrhoea up to week 48 (p=0·023), and more patients assigned raltegravir had grade 3 or 4 rises in alanine aminotransferase (p=0·020) or aspartate aminotransferase (p=0·009).
Elvitegravir used in combination with a ritonavir-boosted protease inhibitor in treatment-experienced patients has similar efficacy and safety to raltegravir. Since elvitegravir can be given once a day compared with twice a day for raltegravir, elvitegravir might improve patients' adherence.
Gilead Sciences.
艾维雷格韦是一种每日一次的 HIV-1 整合酶抑制剂，由利托那韦增强。我们旨在比较艾维雷格韦与拉替拉韦（另一种 HIV-1 整合酶抑制剂）在先前抗逆转录病毒治疗失败的患者中的疗效和安全性。
我们在 13 个国家的 234 个地点进行了一项随机、双盲、双模拟、3 期研究。合格的患者具有每毫升 1000 个拷贝或更高的血浆 HIV RNA，任何 CD4 细胞计数，以及对或 6 个月的经验，至少有两类抗逆转录病毒药物。他们接受了一种开放标签的背景方案，包括一种完全有效的、利托那韦增强的蛋白酶抑制剂和第二种药物。我们通过计算机以 4 个为一组的块大小随机分配（1:1）患者接受艾维雷格韦 150 毫克每日一次（如果与阿扎那韦或洛匹那韦与利托那韦一起使用，则给予 85 毫克剂量）或拉替拉韦 400 毫克每日两次（n=363）。给予安慰剂片剂以掩盖每日剂量的差异。主要终点是通过第 48 周达到并维持病毒学应答（HIV RNA <50 拷贝/毫升）。非劣效性是预先指定的，有 10%的余地。我们进行了改良的意向治疗分析。这项研究在 ClinicalTrials.gov 注册，编号为 NCT00708162。
10 名接受艾维雷格韦治疗的患者和 12 名接受拉替拉韦治疗的患者被排除在分析之外（要么是因为违反方案，要么是因为他们没有接受治疗）。与分配拉替拉韦的 351 名患者中的 203 名（58%）相比，207 名（59%）接受艾维雷格韦治疗的患者达到了病毒学应答（治疗差异 1.1%，95%CI-6.0 至 8.2），达到了非劣效性标准（p=0.001）。与分配拉替拉韦的患者相比，接受艾维雷格韦治疗的患者中有 3 名发生了与研究药物相关的严重不良事件，而分配拉替拉韦的患者中有 7 名发生了严重不良事件；分别有 2 名和 8 名患者死亡。接受艾维雷格韦治疗的患者在第 48 周时报告腹泻的人数更多（p=0.023），而接受拉替拉韦治疗的患者中丙氨酸氨基转移酶（ALT）或天冬氨酸氨基转移酶（AST）升高 3 级或 4 级的人数更多（p=0.020，p=0.009）。
在有经验的患者中，与利托那韦增强的蛋白酶抑制剂联合使用的艾维雷格韦具有与拉替拉韦相似的疗效和安全性。由于艾维雷格韦可以每天服用一次，而拉替拉韦需要每天服用两次，因此艾维雷格韦可能会提高患者的依从性。
吉利德科学公司。
