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齐多夫定耐药突变对齐多夫定-拉米夫定-利托那韦治疗病毒学反应的影响:来自艾滋病临床试验组方案315的1型人类免疫缺陷病毒分离株的基因分型分析。艾滋病临床试验组方案315团队。

Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine-lamivudine-ritonavir: genotypic analysis of human immunodeficiency virus type 1 isolates from AIDS clinical trials group protocol 315.ACTG Protocol 315 Team.

作者信息

Kuritzkes D R, Sevin A, Young B, Bakhtiari M, Wu H, St Clair M, Connick E, Landay A, Spritzler J, Kessler H, Lederman M M

机构信息

Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO 80262, USA.

出版信息

J Infect Dis. 2000 Feb;181(2):491-7. doi: 10.1086/315244.

Abstract

The effect of baseline drug resistance mutations on response to zidovudine, lamivudine, and ritonavir was evaluated in zidovudine-experienced persons infected with human immunodeficiency virus type 1 (HIV-1). Presence of the K70R mutation was associated with significantly higher plasma HIV-1 RNA levels at baseline. However, presence of resistance mutations did not affect the increase in plasma HIV-1 RNA during a 5-week drug washout, nor was there any effect on first-phase virus decay rates after initiation of therapy or on the probability of having plasma HIV-1 RNA levels <100 copies/mL at week 48. Polymorphisms at protease codons 10, 36, and 71 were associated with significantly faster second-phase decay rates. Suppression of plasma HIV-1 RNA despite presence of zidovudine resistance mutations implies that the presence of these mutations does not preclude a durable response to treatment with a potent 3-drug regimen.

摘要

在曾使用齐多夫定的1型人类免疫缺陷病毒(HIV-1)感染者中,评估了基线耐药性突变对齐多夫定、拉米夫定和利托那韦反应的影响。K70R突变的存在与基线时显著更高的血浆HIV-1 RNA水平相关。然而,耐药性突变的存在并不影响5周药物洗脱期内血浆HIV-1 RNA的增加,对治疗开始后的第一阶段病毒衰减率或第48周时血浆HIV-1 RNA水平<100拷贝/mL的概率也没有任何影响。蛋白酶密码子10、36和71处的多态性与显著更快的第二阶段衰减率相关。尽管存在齐多夫定耐药性突变,但血浆HIV-1 RNA仍受到抑制,这意味着这些突变的存在并不排除对有效的三联药物治疗产生持久反应。

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