HIV WITH REDUCED SENSITIVITY TO ZIDOVUDINE (AZT) ISOLATED DURING PROLONGED THERAPY
HIV WITH REDUCED SENSITIVITY TO ZIDOVUDINE (AZT) ISOLATED DURING PROLONGED THERAPY
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DOI：
10.1126/science.2467383
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发表时间：
1989-03-31
期刊：
影响因子：
56.9
通讯作者：
RICHMAN, DD
中科院分区：
文献类型：
--
作者：
LARDER, BA;DARBY, G;RICHMAN, DD
本文应用新近发展的CD 4 + HeLa细胞空斑试验，对一组接受齐多夫定（3“-叠氮-3”-脱氧胸苷，AZT）治疗的艾滋病（AIDS）或艾滋病相关综合征（ARC）患者的HIV分离株进行了药物敏感性试验。来自未处理个体的18个分离物的50%抑制剂量（ID 50）值在0.01 μ M和0.05 μ M之间。相比之下，接受齐多夫定治疗6个月或更长时间的患者的大多数分离株表现出敏感性降低，其特征在于ID 50或ID 95值（或两者）的变化，其中几例患者（5/15）的分离株显示ID 50增加100倍。后者分离株对3“-叠氮基-2”，3“-双脱氧尿苷也不敏感;然而，分离株对2”，3“-双脱氧胞苷、2”，3“-双脱氧-2，3”-双脱氢胸苷或膦甲酸酯仍然敏感。从这一小部分患者样本中无法确定敏感性较低的病毒表型是否会导致临床耐药。这些变异体的出现与患者血浆中病毒p24浓度的一致增加无关，也不预示临床状态的任何突然恶化。需要更广泛的研究来确定临床意义。因此，目前改变艾滋病毒感染者的任何治疗方案都为时过早。
The drug sensitivities of human immunodeficiency virus (HIV) isolates from a group of patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) who were receiving zidovudine (3''-azido-3''-deoxythymidine, AZT) therapy were tested by means of a newly developed plaque assay in CD4+ HeLa cells. Fifty percent inhibitory dose (ID50) values of 18 isolates from untreated individuals ranged between 0.01 .mu.M and 0.05 .mu.M. In contrast, most isolates from patients who had received zidovudine for 6 months or more exhibited decreased sensitivity characterized by changes in ID50 or ID95 values (or both), with isolates from several patients (5/15) showing 100-fold increases in ID50. The latter isolates were also insensitive to 3''-azido-2'',3''-dideoxyuridine; however, the isolates were still sensitive to 2'',3''-dideoxycytidine, 2'',3''-dideoxy-2,3''-didehydrothymidine, or phosphonoformate. It cannot be determined from this small sample of patients whether development of a less sensitive virus phenotype results in clinical resistance. Appearance of such variants was not associated with a consistent increase in viral p24 concentrations in patient plasma and did not herald any sudden deterioration in clinical status. More extensive studies are required to determine the clinical significance. Thus, it would be premature to alter any treatment protocols for HIV-infected individuals at present.