LOSS OF SYNERGISTIC RESPONSE TO COMBINATIONS CONTAINING AZT IN AZT-RESISTANT HIV-1

被引：16
作者：
COX, SW [1 ]
ALBERT, J [1 ]
WAHLBERG, J [1 ]
UHLEN, M [1 ]
WAHREN, B [1 ]
机构：
[1] ROYAL INST TECHNOL,DEPT BIOCHEM & BIOTECHNOL,S-10044 STOCKHOLM 70,SWEDEN
来源：
AIDS RESEARCH AND HUMAN RETROVIRUSES | 1992年 / 8卷 / 07期
关键词：
D O I：
10.1089/aid.1992.8.1229
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
The use of combination chemotherapy for the treatment of HIV-1 infection offers promise for overcoming the problems of toxicity and development of resistance. Primary HIV-1 isolates from three patients before and after treatment with azidothymidine (AZT) were examined for sensitivity to AZT and synergistic response to three different combinations of drugs: AZT + fluorothymidine (FLT), AZT + dideoxyinosine (ddI), and FLT + ddI. All three patients initially harbored AZT-sensitive virus, but posttherapy isolates were resistant to AZT. The pretreatment, AZT-sensitive virus from each patient showed synergistic inhibition by the combinations of AZT + FLT, AZT + ddI, and FLT + ddI. In contrast, the posttreatment, AZT-resistant virus showed only addition or antagonism by the combinations containing AZT, whereas the synergistic response to the combination of FLT + ddI was preserved. Our study argues for early intervention with combination chemotherapy, since after development of resistance, AZT no longer showed synergy but addition or antagonism in combination with other drugs. After resistance to AZT has developed, combination chemotherapy not involving AZT may offer advantages over continued mono- or combination therapy involving AZT.
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收藏
页码：1229 / 1234
页数：6
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