Phillips A N, Katlama C, Barton S, Vella S, Blaxhult A, Clotet B, Goebel F D, Hirschel B, Pedersen C, Lundgren J D
Royal Free Hospital School of Medicine, London, UK.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Mar 1;17(3):239-44. doi: 10.1097/00042560-199803010-00009.
To evaluate survival according to use of different nucleoside drugs in a routine clinical setting, we studied a large group of zidovudine-treated patients seen in clinics across Europe. A total of 3128 subjects was recruited to the observational, prospective EuroSIDA study in May 1994. These were consecutive patients (up to a predefined limit) seen at outpatient clinics in 37 centers from 16 European countries and followed at 6-month intervals by use of standardized forms completed by clinicians at the respective centers. This report concerns 2367 subjects who began antiretroviral therapy with a regime that included zidovudine either before study entry or during the course of follow-up. Cox proportional hazards models were fitted, with use of other antiretroviral drugs, CD4 count, and date of development of AIDS fitted as time-dependent covariates. Survival times from start of therapy were left truncated at study entry to avoid survival bias. In addition to zidovudine, antiretroviral drugs used included didanosine (ddI) (n = 1119; median 1.6 years after starting zidovudine), dideoxycytidine (ddC) (n = 592; median 1.9 years after starting zidovudine), stavudine (d4T) (n = 241; median 2.9 years after starting zidovudine) and lamivudine (3TC) (n = 33 ; median 2.7 years after starting zidovudine). Of the 2367 patients, 613 died during follow-up. Overall, risk of death was reduced in those zidovudine-treated patients who began at least one other nucleoside analogue drug with or after taking zidovudine (relative hazard [RH], 0.61; 95% confidence interval [CI], 0.51-0.72, adjusting for CD4 count, development of AIDS, and age). Fitting each drug separately, there was a larger association with reduced mortality for starting 3TC (RH, 0.41; 95% CI, 0.28-0.62) than for starting ddl (RH, 0.79; 95% CI, 0.67-0.93), ddC (RH, 0.74; 95% CI, 0.59-0.92) or d4T (RH, 0.67; 95% CI, 0.49-0.91). These results suggest that the beneficial effect of nucleoside combination therapy identified in controlled trials can be seen in routine clinical practice.
为了在常规临床环境中根据不同核苷类药物的使用情况评估生存率，我们研究了一大群在欧洲各地诊所接受齐多夫定治疗的患者。1994年5月，共有3128名受试者被纳入观察性前瞻性欧洲艾滋病临床研究（EuroSIDA）。这些是来自16个欧洲国家37个中心门诊诊所的连续患者（达到预先设定的上限），各中心的临床医生每隔6个月使用标准化表格对其进行随访。本报告涉及2367名受试者，他们在研究入组前或随访期间开始接受包含齐多夫定的抗逆转录病毒治疗方案。采用Cox比例风险模型，将使用的其他抗逆转录病毒药物、CD4细胞计数和艾滋病发病日期作为时间依赖性协变量进行拟合。为避免生存偏倚，治疗开始后的生存时间在研究入组时进行左截尾。除齐多夫定外，使用的抗逆转录病毒药物包括去羟肌苷（ddI）（n = 1119；开始使用齐多夫定后中位数1.6年）、双脱氧胞苷（ddC）（n = 592；开始使用齐多夫定后中位数1.9年）、司他夫定（d4T）（n = 241；开始使用齐多夫定后中位数2.9年）和拉米夫定（3TC）（n = 33；开始使用齐多夫定后中位数2.7年）。在2367名患者中，613人在随访期间死亡。总体而言，在服用齐多夫定期间或之后开始使用至少一种其他核苷类似物药物的齐多夫定治疗患者中，死亡风险降低（相对风险[RH]，0.61；95%置信区间[CI]，0.51 - 0.72，校正CD4细胞计数、艾滋病发病情况和年龄）。分别对每种药物进行拟合，开始使用3TC（RH，0.41；95% CI，0.28 - 0.62）与开始使用ddI（RH，0.79；95% CI，0.67 - 0.93）、ddC（RH，0.74；95% CI，0.59 - 0.92）或d4T（RH，0.67；95% CI，0.49 - 0.91）相比，与死亡率降低的关联更大。这些结果表明，在对照试验中确定的核苷类联合治疗的有益效果在常规临床实践中也可见到。
