齐多夫定加拉米夫定与司他夫定加拉米夫定的开放性随机对照试验。

An open randomized controlled trial of zidovudine plus lamivudine versus stavudine plus lamivudine.

作者信息

Foudraine N A, de Jong J J, Jan Weverling G, van Benthem B H, Maas J, Keet I P, Jurriaans S, Roos M T, Vandermeulen K, de Wolf F, Lange J M

机构信息

Department of Public Health and Environment, Academic Medical Centre, University of Amsterdam, The Netherlands.

出版信息

AIDS. 1998 Aug 20;12(12):1513-9. doi: 10.1097/00002030-199812000-00014.

DOI:10.1097/00002030-199812000-00014

PMID:9727573

Abstract

OBJECTIVE

To compare the antiretroviral effect and safety of zidovudine (ZDV)-lamivudine (3TC) with that of stavudine (d4T)-3TC.

METHODS

In an open randomized controlled trial antiretroviral therapy-naive patients who had CD4+ counts > or = 200 x 10(6)/l and plasma HIV RNA load > or = 10000 copies/ml were randomized to receive ZDV-3TC (200 mg three times daily and 150 mg twice daily, respectively) or d4T-3TC (40 mg and 150 mg, both twice daily). If the plasma HIV RNA level at week 8 or thereafter was > 500 copes/ml, indinavir was added at the next scheduled visit. Genotypic resistance analysis of the reverse transcriptase gene was performed at week 0 and 12. Results over 24 weeks were reported.

RESULTS

Forty-seven patients were treated (24 took ZDV-3TC; 23 took d4T-3TC). Plasma HIV RNA levels decreased from median 4.80 to 3.15 log10 copies/ml (ZDV-3TC, P < 0.0001) and from 4.98 to 3.03 log10 copies/ml (d4T-3TC, P < 0.0001) after 12 weeks of treatment. Indinavir was added at week 12 in 11 out of 21 patients with ZDV-3TC and in 10 out of 22 patients with d4T-3TC. Median virus load at week 24 was 2.41 log10 and 2.29 log10 copies/ml (P=0.14), respectively. Seventy-five per cent (15 out of 20; ZDV-3TC) and 95% (18 out of 19; d4T-3TC) of patients had a virus load of < 500 copies/ml. Genomic evidence for 3TC resistance was found in all patients tested (11/11 ZDV-3TC and 12/12 d4T-3TC). At week 12, CD4 cell counts had increased with a median of 110 x 10(6)/l in the ZDV-3TC group (baseline, 315 x 10(6)/l) and a median of 115 x 10(6)/l in the d4T-3TC group (baseline 290 x 10(6)/l). At week 24, the median increases were 90 and 120 x 10(6)/l, respectively. Overall the increase of CD4+ cells was higher in the d4T-3TC group (P=0.02).

CONCLUSION

d4T-3TC is at least as effective as ZDV-3TC, but 3TC resistance emerged in all patients investigated. The virological response of the dual nucleoside combination is of short duration. However, after addition of indinavir the virus load could be reduced to < 500 copies/ml in the majority of patients. The increase in CD4+ cell count was significantly greater in the d4T-3TC group. To prevent 3TC resistance, the drug should not be used in regimens containing only two nucleosides, irrespective the virus load at baseline.

摘要

目的

比较齐多夫定（ZDV）-拉米夫定（3TC）与司他夫定（d4T）-3TC的抗逆转录病毒效果及安全性。

方法

在一项开放性随机对照试验中，将CD4 +细胞计数≥200×10⁶ /L且血浆HIV RNA载量≥10000拷贝/ml的初治抗逆转录病毒治疗患者随机分组，分别接受ZDV-3TC（分别为每日3次，每次200mg和每日2次，每次150mg）或d4T-3TC（均为每日2次，每次40mg和150mg）治疗。如果在第8周或之后血浆HIV RNA水平> 500拷贝/ml，则在下一次预定访视时加用茚地那韦。在第0周和第12周进行逆转录酶基因的基因型耐药性分析。报告了24周的结果。

结果

47例患者接受治疗（24例接受ZDV-3TC治疗；23例接受d4T-3TC治疗）。治疗12周后，血浆HIV RNA水平从中位数4.80 log₁₀拷贝/ml降至3.15 log₁₀拷贝/ml（ZDV-3TC组，P < 0.0001），从4.98 log₁₀拷贝/ml降至3.03 log₁₀拷贝/ml（d4T-3TC组，P < 0.0001）。接受ZDV-3TC治疗的21例患者中有11例在第12周加用茚地那韦，接受d4T-3TC治疗的22例患者中有10例在第12周加用茚地那韦。第24周时病毒载量中位数分别为2.41 log₁₀和2.29 log₁₀拷贝/ml（P = 0.14）。75%（20例中的15例；ZDV-3TC组）和95%（19例中的18例；d4T-3TC组）的患者病毒载量< 500拷贝/ml。在所有检测患者（11/11例ZDV-3TC组和12/12例d4T-3TC组）中均发现了对3TC耐药的基因证据。在第12周时，ZDV-3TC组CD4细胞计数中位数增加了110×10⁶ /L（基线为315×10⁶ /L），d4T-3TC组CD4细胞计数中位数增加了115×10⁶ /L（基线为290×10⁶ /L）。在第24周时，中位数增加分别为90和120×10⁶ /L。总体而言，d4T-3TC组CD4 +细胞增加更高（P = 0.02）。

结论

d4T-3TC至少与ZDV-3TC一样有效，但在所有研究患者中均出现了对3TC的耐药。双核苷组合的病毒学反应持续时间较短。然而，加用茚地那韦后，大多数患者的病毒载量可降至< 500拷贝/ml。d4T-3TC组CD4 +细胞计数增加显著更大。为防止对3TC耐药，无论基线病毒载量如何，该药均不应在仅含两种核苷类药物的方案中使用。