N348I in HIV-1 Reverse Transcriptase Counteracts the Synergy Between Zidovudine and Nevirapine

被引：6
作者：
Yap, Soo Huey [1 ,2 ]
Herman, Brian D. [3 ]
Radzio, Jessica [3 ]
Sluis-Cremer, Nicolas [3 ]
Tachedjian, Gilda [1 ,4 ,5 ]
机构：
[1] Burnet Inst, Ctr Virol, Retroviral Biol & Antivirals Lab, Melbourne, Vic 3001, Australia
[2] Monash Univ, Sch Appl Sci & Engn, Churchill, Vic, Australia
[3] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA
[4] Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia
[5] Monash Univ, Dept Med, Clayton, Vic 3168, Australia
来源：
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES | 2012年 / 61卷 / 02期
基金：
美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词：
HIV-1 drug resistance; reverse transcriptase inhibitors; antiretroviral therapy; N348I; connection subdomain; C-terminal domain; combination therapy; zidovudine; nevirapine; IMMUNODEFICIENCY-VIRUS TYPE-1; CONNECTION DOMAIN; ANTIRETROVIRAL THERAPY; H CLEAVAGE; MUTATIONS; RESISTANCE; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHOSPHOROLYSIS; COMBINATION; INHIBITORS;
D O I：
10.1097/QAI.0b013e3182657990
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 efficacy of regimens that include both zidovudine and nevirapine can be explained by the synergistic interactions between these drugs. N348I in HIV-1 reverse transcriptase confers decreased susceptibility to zidovudine and nevirapine. Here, we demonstrate that N348I reverses the synergistic inhibition of HIV-1 by zidovudine and nevirapine. Also, the efficiency of zidovudine-monophosphate excision in the presence of nevirapine is greater for N348I HIV-1 reverse transcriptase compared with the wild-type enzyme. These data help explain the frequent selection of N348I in regimens that contain zidovudine and nevirapine, and suggest that the selection of N348I should be monitored in resource-limited settings where these drugs are routinely used.
引用
收藏
页码：153 / 157
页数：5
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