Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy

被引:90
作者
Pellegrin, I
Izopet, J
Reynes, J
Denayrolles, M
Montes, B
Pellegrin, JL
Massip, P
Puel, J
Fleury, H
Segondy, M
机构
[1] Bordeaux Univ Hosp, Dept Virol, Bordeaux, France
[2] Bordeaux Univ Hosp, Dept Infect Dis, Bordeaux, France
[3] Toulouse Univ Hosp, Dept Virol, Toulouse, France
[4] Toulouse Univ Hosp, Dept Infect Dis, Toulouse, France
[5] Montpellier Univ Hosp, Dept Virol, Montpellier, France
[6] Montpellier Univ Hosp, Dept Infect Dis, Montpellier, France
关键词
zidovudine; stavudine; lamivudinel; HIV-1; reverse transcriptase; resistance mutation;
D O I
10.1097/00002030-199909100-00014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: Assessment of genotypic changes in the reverse transcriptase gene of HIV-1 occurring in antiretroviral naive patients treated by stavudine plus didanosine combination therapy. Methods: Sequence analysis (codons 1-230) was-performed after amplification of the reverse transcriptase gene from plasma samples collected at baseline and at the end of treatment from 39 previously treatment-naive patients treated for 24-48 weeks. Results: At baseline, mutations associated with zidovudine resistance were detected in plasma from two patients: Asp67Asn/Lys219Gln and Leu210Trp. Among the 39 subjects, 18 (46%) developed mutations: one developed the Val75Thr/Ala mutation, four (10%) developed a Gln151Met multidrug-resistance mutation (MDR), associated in one of them with the Phe77Leu and the Phe116Tyr MDR mutations and 14 (36%) developed one or more zidovudine-specific mutations (Met41Leu, Asp67Asn, Lys70Arg, Leu210Trp, Thr215Tyr/Phe). The development of a Met41Leu zidovudine-specific mutation was associated with the development of a Gln151Met mutation in one patient. Other reverse transcriptase mutations known to confer resistance to nucleoside analogues were not detected. At inclusion, there was no statistical difference in HIV-1 load between patients who developed resistance mutations and those who did not. RNA HIV-1 load decrease was higher (P = 0.05) in patients who maintained a wild-type reverse transcriptase genotype (-2.22 log(10) copies/ml) than in patients who developed resistance mutations (-1.14 log(10) copies/ml). Conclusion: Stavudine/didanosine combination therapy is associated with emergence of zidovudine-related resistance or MDR mutations in naive patients. These findings should be considered when optimizing salvage therapy for patients who have received a treatment including stavudine/didanosine combination. (C) 1999 Lippincott Williams & Wilkins.
引用
收藏
页码:1705 / 1709
页数:5
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