Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
Int J Epidemiol. 2012 Apr;41(2):448-59. doi: 10.1093/ije/dys022.
Although generic anti-retroviral drugs are in common use throughout the developing world, studies comparing their clinical effectiveness with that of proprietary formulations are lacking.
We analysed observational data from a large cohort of adults on anti-retroviral therapy (ART) to assess potential differences between generic and proprietary zidovudine (ZDV) formulations in post-90-day mortality, 'programme failure' (a composite of death, follow-up losses and withdrawals) and other clinical outcomes. We accounted for drug exposure in three ways: an 'initial dispensation' approach that categorized patients according to the first prescription; 'time-varying' approach that attributed an outcome to the formulation taken at the time of event; and 'predominant exposure' approach that considered only those with >75% exposure to either brand or generic ZDV. Proprietary formulations were used as the reference group in all adjusted Cox proportional hazard regressions.
Among 14 736 patients eligible for analysis, 7277 (49%) initiated a generic formulation of ZDV and 7459 (51%) initiated a proprietary formulation. When categorized according to initial dispensation, no difference in post-90-day mortality was observed between the two groups [adjusted hazard ratio (AHR): 0.93, 95% confidence interval (CI): 0.77-1.12]. Similar findings were noted when drug formulation was treated as a time-varying exposure (AHR: 1.15, 95% CI: 0.89-1.48) when analysis was limited to those with a predominant exposure to one formulation or the other (AHR: 0.59, 95% CI: 0.24-1.49). Results were consistent across all approaches when programme failure was considered as an outcome. No longitudinal differences were detected between formulations for CD4 response, weight change and haemoglobin concentration. Generic ZDV formulations were associated with slight decreases in single-drug substitution.
In this large programmatic cohort of adults starting ZDV-based first-line therapy, clinical outcomes appeared similar among patients on generic or proprietary formulations. These findings support continued use of generic anti-retroviral drug formulations in resource-constrained settings.
虽然通用的抗逆转录病毒药物在发展中国家被广泛使用，但缺乏比较其临床疗效与专利制剂的研究。
我们分析了来自接受抗逆转录病毒治疗（ART）的大量成年人队列的观察性数据，以评估在 90 天后死亡率、“方案失败”（死亡、随访损失和退出的综合）和其他临床结果方面，通用和专利齐多夫定（ZDV）制剂之间的潜在差异。我们通过三种方式考虑药物暴露：一种“初始分配”方法，根据第一个处方对患者进行分类；一种“时变”方法，将结果归因于事件发生时服用的制剂；以及一种“主要暴露”方法，仅考虑那些对任何品牌或通用 ZDV 的暴露率超过 75%的制剂。在所有调整后的 Cox 比例风险回归中，专利制剂均被用作参考组。
在 14736 名符合分析条件的患者中，7277 名（49%）启动了 ZDV 的通用制剂，7459 名（51%）启动了专利制剂。当根据初始分配进行分类时，两组之间在 90 天后死亡率方面没有差异[调整后的危险比（AHR）：0.93，95%置信区间（CI）：0.77-1.12]。当将药物制剂视为时变暴露时，也观察到了类似的发现（AHR：1.15，95%CI：0.89-1.48），当分析仅限于主要暴露于一种制剂的患者时（AHR：0.59，95%CI：0.24-1.49）。当将方案失败视为结果时，所有方法的结果都是一致的。在 CD4 反应、体重变化和血红蛋白浓度方面，未发现制剂之间存在纵向差异。通用 ZDV 制剂与单一药物替代略有减少有关。
在接受 ZDV 为基础的一线治疗的大型方案队列中，使用通用或专利制剂的患者的临床结果似乎相似。这些发现支持在资源有限的环境中继续使用通用抗逆转录病毒药物制剂。
