Wainberg M A, Rooke R, Tremblay M, Li X, Parniak M A, Gao Q, Yao X J, Tsoukas C, Montaner J, Fanning M, Ruedy J
St Paul's Hospital, University of British Columbia, Vancouver, British Columbia; Toronto General Hospital, University of Toronto, Toronto, Ontario; and Jewish General Hospital, Montreal General Hospital and McGill aids Centre, McGill University, Montreal, Quebec.
Can J Infect Dis. 1991 Spring;2(1):5-11. doi: 10.1155/1991/124860.
A number of laboratories have now independently confirmed that zidovudine (AZT)-resistant strains of human immunodeficiency virus type 1 (HIV-1) may be isolated from patients undergoing prolonged therapy with this drug. In certain instances, such drug-resistant viral isolates have been obtained from patients with clinical acquired immune deficiency syndrome (aids), while in others, isolation of drug-resistant strains has been achieved in the case of HIV seropositive, asymptomatic subjects. Most of the evidence points to a series of mutations within the polymerase gene of HIV-1, which encodes viral reverse transcriptase, as being responsible for development of the drug-resistant phenotype. It further appears that over 50% of patients treated with AZT for periods longer than six months are likely to yield drug-resistant strains of HIV-1 in their circulation. Furthermore, the development of drug resistance soon after initiation of AZT therapy may potentially be correlated with the likelihood of AZT treatment failure. In several instances, cross resistance has been observed between AZT and other nucleosides being considered for potential therapy of HIV-1-associated disease.
现在有多个实验室已独立证实，接受齐多夫定（AZT）长期治疗的患者体内可能分离出1型人类免疫缺陷病毒（HIV-1）的AZT耐药毒株。在某些情况下，此类耐药病毒分离株是从患有临床获得性免疫缺陷综合征（艾滋病）的患者中获得的，而在其他情况下，在HIV血清阳性的无症状受试者中也实现了耐药毒株的分离。大多数证据表明，HIV-1聚合酶基因（该基因编码病毒逆转录酶）内的一系列突变是耐药表型产生的原因。进一步看来，接受AZT治疗超过6个月的患者中，超过50%的人血液循环中可能会产生HIV-1耐药毒株。此外，AZT治疗开始后不久出现耐药性可能与AZT治疗失败的可能性潜在相关。在一些情况下，已观察到AZT与其他正考虑用于HIV-1相关疾病潜在治疗的核苷之间存在交叉耐药性。
