Sale M, Sheiner L B, Volberding P, Blaschke T F
Division of Clinical Pharmacology, Stanford University School of Medicine, Calif.
Clin Pharmacol Ther. 1993 Nov;54(5):556-66. doi: 10.1038/clpt.1993.188.
To examine predictors of magnitude of CD4+ response to treatment of human immunodeficiency virus (HIV) infection with zidovudine.
This was a post hoc analysis of randomized placebo-controlled clinical trial in a multicenter trial, 1423 asymptomatic HIV-positive subjects with CD4+ cell counts less than 500 mm-3 were given 500 mg/day zidovudine, 1500 mg/day zidovudine, or placebo. The main outcome measure was change in the CD4+ cell counts over time.
This study suggests that earlier treatment with zidovudine results in a larger increment in the CD4+ cell count. In addition, the increment in CD4+ cell count is very long lived. However, drug exposure was not found to be a predictor of response to treatment in the dose range studied.
A parametric model of disease progression can be estimated with use of data collected in a conventionally designed study. These parametric models may provide insight into the optimal use of drugs. This model suggests that zidovudine does not change the underlying course of HIV infection but simply delays the time course. The model also suggests that the magnitude of this delay is larger when treatment is begun earlier in the course of the disease.
研究齐多夫定治疗人类免疫缺陷病毒（HIV）感染时CD4 +反应幅度的预测因素。
这是一项多中心随机安慰剂对照临床试验的事后分析，1423名CD4 +细胞计数低于500/mm³的无症状HIV阳性受试者分别接受500mg/天齐多夫定、1500mg/天齐多夫定或安慰剂治疗。主要结局指标是CD4 +细胞计数随时间的变化。
本研究表明，早期使用齐多夫定治疗可使CD4 +细胞计数有更大幅度的增加。此外，CD4 +细胞计数的增加持续时间很长。然而，在所研究的剂量范围内，未发现药物暴露是治疗反应的预测因素。
利用传统设计研究中收集的数据可以估计疾病进展的参数模型。这些参数模型可能有助于深入了解药物的最佳使用方法。该模型表明，齐多夫定不会改变HIV感染的潜在病程，只是简单地延迟了病程。该模型还表明，在疾病病程早期开始治疗时，这种延迟的幅度更大。
