Schmit J C, Cogniaux J, Hermans P, Van Vaeck C, Sprecher S, Van Remoortel B, Witvrouw M, Balzarini J, Desmyter J, De Clercq E, Vandamme A M
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J Infect Dis. 1996 Nov;174(5):962-8. doi: 10.1093/infdis/174.5.962.
A human immunodeficiency virus type 1 (HIV-1)-seropositive patient was treated sequentially with the dideoxynucleoside (ddN) analogues zidovudine, didanosine, zalcitabine, stavudine, and lamivudine and the nonnucleoside HIV-1-specific reverse transcriptase inhibitor (NNRTI) loviride (alpha-APA). Accumulation of drug resistance mutations (mainly V75I, F77L, K103N, F116Y, Q151M, and M184V) eventually resulted in a strain that was genotypically and phenotypically resistant to all tested ddNs and the majority of NNRTIs. However, the multidrug-resistant virus retained wild type sensitivities to drugs such as foscarnet, phosphonomethoxyethyl adenine, dextran sulfate, JM3100, saquinavir, and NNRTI TSAO-m3T. Drug-resistant isolates showed replication kinetics and infectivity in an in vitro peripheral blood mononuclear cell system similar to those of the wild type isolate from the same patient. The multi-ddN-resistant isolate was not eliminated in a competition culture with the wild type isolate. Sequential therapy did not prevent the appearance of multidrug-resistant virus with a conserved replication rate.
一名1型人类免疫缺陷病毒（HIV-1）血清反应阳性患者先后接受了双脱氧核苷（ddN）类似物齐多夫定、去羟肌苷、扎西他滨、司他夫定和拉米夫定，以及非核苷类HIV-1特异性逆转录酶抑制剂（NNRTI）洛韦胺（α-APA）的治疗。耐药突变（主要是V75I、F77L、K103N、F116Y、Q151M和M184V）的积累最终产生了一种在基因型和表型上对所有测试的ddN以及大多数NNRTI均耐药的毒株。然而，这种多重耐药病毒对膦甲酸钠、磷甲氧基乙基腺嘌呤、硫酸葡聚糖、JM3100、沙奎那韦和NNRTI TSAO-m3T等药物仍保持野生型敏感性。耐药分离株在体外外周血单个核细胞系统中的复制动力学和感染性与来自同一患者的野生型分离株相似。在与野生型分离株的竞争培养中，多重ddN耐药分离株未被清除。序贯治疗未能阻止具有保守复制率的多重耐药病毒的出现。
