Mohri H, Singh M K, Ching W T, Ho D D
Aaron Diamond AIDS Research Center, Department of Medicine and Microbiology, New York University School of Medicine, NY 10016.
Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):25-9. doi: 10.1073/pnas.90.1.25.
A nonselective ex vivo assay was used to directly detect and quantify zidovudine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) in the blood of treated and untreated patients. In contrast to previous reports, drug-resistant virus was detected in peripheral blood mononuclear cells of a few of the patients who had never received AZT. The AZT resistance of HIV-1 isolates from one untreated individual was confirmed by further susceptibility studies in vitro and by the finding of a characteristic mutation (Lys-->Arg at codon 70) in the reverse transcriptase. In patients who were clinically stable while on AZT, HIV-1 titers in plasma and mononuclear cells were generally low but resistant viruses already predominated. In those individuals who were deteriorating despite AZT administration, high levels of viremia were observed, and the resistance phenotype was nearly universal. These findings serve to emphasize the magnitude of the AZT-resistance problem in patients on drug treatment.
采用非选择性体外试验直接检测和定量接受治疗及未接受治疗患者血液中对齐多夫定（AZT）耐药的人类免疫缺陷病毒1型（HIV-1）。与之前的报道不同，在从未接受过AZT治疗的少数患者的外周血单核细胞中检测到了耐药病毒。通过进一步的体外敏感性研究以及在逆转录酶中发现一个特征性突变（密码子70处赖氨酸→精氨酸），证实了来自一名未接受治疗个体的HIV-1分离株对AZT耐药。在接受AZT治疗时临床稳定的患者中，血浆和单核细胞中的HIV-1滴度通常较低，但耐药病毒已占主导。在那些尽管接受了AZT治疗但病情仍在恶化的个体中，观察到高病毒血症水平，且耐药表型几乎普遍存在。这些发现强调了接受药物治疗患者中AZT耐药问题的严重性。
