Cain Lauren E, Phillips Andrew, Olson Ashley, Sabin Caroline, Jose Sophie, Justice Amy, Tate Janet, Logan Roger, Robins James M, Sterne Jonathan A C, van Sighem Ard, Reiss Peter, Young James, Fehr Jan, Touloumi Giota, Paparizos Vasilis, Esteve Anna, Casabona Jordi, Monge Susana, Moreno Santiago, Seng Rémonie, Meyer Laurence, Pérez-Hoyos Santiago, Muga Roberto, Dabis François, Vandenhende Marie-Anne, Abgrall Sophie, Costagliola Dominique, Hernán Miguel A
Clin Infect Dis. 2015 Apr 15;60(8):1262-8. doi: 10.1093/cid/ciu1167. Epub 2015 Jan 6.
Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience.
We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes.
A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone.
Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens.
当前临床指南将由利托那韦增强的阿扎那韦或利托那韦增强的洛匹那韦与核苷类逆转录酶抑制剂(NRTI)骨干组成的方案列为推荐的和替代的一线抗逆转录病毒方案。然而,这些指南是基于随机临床试验的有限证据和临床经验制定的。
我们利用2004年至2013年在欧洲和美国进行的人类免疫缺陷病毒(HIV)感染个体前瞻性研究的数据,比较了这些方案在临床、免疫和病毒学结果方面的差异。未接受过抗逆转录病毒治疗且无艾滋病的个体从开始洛匹那韦或阿扎那韦方案治疗时开始随访。我们估计了阿扎那韦与洛匹那韦方案对每种结果的“意向性治疗”效果。
共有6668人开始使用洛匹那韦方案(213人死亡,457人发生艾滋病定义疾病或死亡),4301人开始使用阿扎那韦方案(83人死亡,157人发生艾滋病定义疾病或死亡)。阿扎那韦与洛匹那韦方案调整后的意向性治疗风险比,死亡为0.70(95%置信区间[CI],0.53 - 0.91),艾滋病定义疾病或死亡为0.67(95%CI,0.55 - 0.82),12个月时病毒学失败为0.91(95%CI,0.84 - 0.99)。阿扎那韦组12个月时CD4细胞计数平均增加8.15(95%CI,-0.13至16.43)个/微升。估计值因NRTI骨干不同而有所差异。
我们的估计结果表明,与洛匹那韦方案相比,阿扎那韦方案的死亡率更低、艾滋病定义疾病的发病率更低、12个月时CD4细胞计数增加更多且12个月时病毒学失败风险更小。