Willig James H, Abroms Sarah, Westfall Andrew O, Routman Justin, Adusumilli Sunil, Varshney Mohit, Allison Jeroan, Chatham Ashlee, Raper James L, Kaslow Richard A, Saag Michael S, Mugavero Michael J
Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
AIDS. 2008 Oct 1;22(15):1951-60. doi: 10.1097/QAD.0b013e32830efd79.
Data on initial antiretroviral regimen longevity predates the arrival of newer nucleoside reverse transcriptase inhibitor backbones and once-daily regimens. Modern regimens are thought to possess greater tolerability and convenience. We hypothesized this would translate into greater durability.
Retrospective study of antiretroviral-naive patients starting treatment at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic 1 January 2000-31 July 2007. Two periods of antiretroviral initiation were identified, prior and after August 2004 (arrival of once-daily fixed-dose regimens). Kaplan-Meier survival analyses of regimen durability by time period and regimen characteristics were performed. Staged Cox proportional hazards models evaluated the roles of dosing complexity and composition in explaining differences in regimen durability between study periods.
Overall 542 patients started antiretroviral drugs (n = 309, January 2000-July 2004; n = 233, August 2004-July 2007). Median durability was 263 days longer in after August 2004 regimens. Regimens started before August 2004 had increased hazards for discontinuation relative to after August 2004 regimens [hazard ratio (HR) = 1.44; 95% confidence interval (CI) = 1.03-2.02]. Time period of initiation lost statistical significance when the model included dosing frequency (HR = 1.92 for at least twice daily vs. daily; 95% CI = 1.29-2.88). As regimen composition variables were added, time period and dosing frequency lost significance. Increased hazards of discontinuation were observed with didanosine or stavudine relative to abacavir or tenofovir use (HR = 1.92; 95% CI = 1.29-2.88) and all third drugs compared with non-nucleoside reverse transcriptase inhibitor-based regimens (triple-nucleoside reverse transcriptase inhibitor HR = 1.76; 95% CI = 1.14-2.73; unboosted-protease inhibitor HR = 1.58; 95% CI = 1.02-2.46; boosted-protease inhibitor HR = 1.57; 95% CI = 1.02-2.41). Affective mental health disorders increased the hazard of discontinuation in all models.
Durability of contemporary once-daily fixed-dose antiretroviral regimens has significantly eclipsed the duration of earlier antiretroviral drug options. Our results indicate this is due to both more convenient dosing and improved tolerability of modern antiretroviral regimens.
关于初始抗逆转录病毒治疗方案持久性的数据早于新型核苷类逆转录酶抑制剂主干药物和每日一次治疗方案的出现。现代治疗方案被认为具有更高的耐受性和便利性。我们推测这将转化为更高的持久性。
对2000年1月1日至2007年7月31日在阿拉巴马大学伯明翰分校1917 HIV/AIDS诊所开始治疗的未接受过抗逆转录病毒治疗的患者进行回顾性研究。确定了两个抗逆转录病毒治疗起始阶段，2004年8月之前和之后（每日一次固定剂量治疗方案出现之后）。按时间段和治疗方案特征对治疗方案持久性进行了Kaplan-Meier生存分析。采用分段Cox比例风险模型评估给药复杂性和组成在解释研究阶段之间治疗方案持久性差异方面的作用。
共有542例患者开始使用抗逆转录病毒药物（2000年1月至2004年7月为309例；2004年8月至2007年7月为233例）。2004年8月之后的治疗方案中位持久性长263天。与2004年8月之后的治疗方案相比，2004年8月之前开始的治疗方案停药风险增加[风险比（HR）=1.44；95%置信区间（CI）=1.03 - 2.02]。当模型纳入给药频率时，起始时间段失去统计学意义（每日至少两次给药与每日一次给药相比，HR = 1.92；95% CI = 1.29 - 2.88）。随着治疗方案组成变量的加入，时间段和给药频率失去意义。与使用阿巴卡韦或替诺福韦相比，使用去羟肌苷或司他夫定观察到停药风险增加（HR = 1.92；95% CI = 1.29 - 2.88），与基于非核苷类逆转录酶抑制剂的治疗方案相比，所有第三种药物均如此（三联核苷类逆转录酶抑制剂HR = 1.76；95% CI = 1.14 - 2.73；未增强的蛋白酶抑制剂HR = 1.58；95% CI = 1.02 - 2.46；增强型蛋白酶抑制剂HR = 1.57；95% CI = 1.02 - 2.41）。在所有模型中，情感性精神障碍增加了停药风险。
当代每日一次固定剂量抗逆转录病毒治疗方案的持久性显著超过了早期抗逆转录病毒药物选择的持续时间。我们的结果表明，这是由于现代抗逆转录病毒治疗方案给药更方便且耐受性更好。
