Multiple drug resistance to nucleoside analogues and nonnucleoside reverse transcriptase inhibitors in an efficiently replicating human immunodeficiency virus type 1 patient strain

被引:107
作者
Schmit, JC
Cogniaux, J
Hermans, P
VanVaeck, C
Sprecher, S
VanRemoortel, B
Witvrouw, M
Balzarini, J
Desmyter, J
DeClercq, E
Vandamme, AM
机构
[1] FREE UNIV BRUSSELS, HOP ST PIERRE, BRUSSELS, BELGIUM
[2] INST PASTEUR, BRUSSELS, BELGIUM
关键词
D O I
10.1093/infdis/174.5.962
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-m(3)T. 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.
引用
收藏
页码:962 / 968
页数:7
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