HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy.
HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy.
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HIV-1 逆转录酶连接域突变：出现动态及其对联合抗逆转录病毒治疗成功的影响。
DOI：
10.1086/655764
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
SwissHIVCohortStudy
中科院分区：
文献类型：
--
作者：
vonWyl,Viktor;Ehteshami,Maryam;Demeter,LisaM;Burgisser,Philippe;Nijhuis,Monique;Symons,Jori;Yerly,Sabine;Boni,Jurg;Klimkait,Thomas;Schuurman,Rob;Ledergerber,Bruno;Gotte,Matthias;Gunthard,HuldrychF;SwissHIVCohortStudy
Background.Factors promoting the emergence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) connection domain mutations and their effect on antiretroviral therapy (ART) are still largely undetermined.We investigated this matter by analyzing genotypic resistance tests covering 400 amino acid positions in the RT of HIV-1 subtype B viruses and corresponding treatment histories and laboratory measurements.Methods.The emergence of connection domain mutations was studied in 334 patients receiving monotherapy or dual therapy with thymidine analogues at the time of the genotypic resistance test. Response to subsequent combination ART (cART) was analyzed using Cox regression for 291 patients receiving unboosted protease inhibitors. Response was defined by ever reaching an HIV RNA level <50 copies/mL during the first cART.Results.The connection domain mutations N348I, R356K, R358K, A360V, and A371V were more frequently observed in ART-exposed than ART-naive patients, of which only N348I and A360V were nonpolymorphic (with a prevalence of <1.5% in untreated patients). N348I correlated with M184V and predominantly occurred in patients receiving lamivudine and zidovudine concomitantly. A360V was not associated with specific drug combinations and was found to emerge later than M184V or thymidine analogue mutations. Nonpolymorphic connection domain mutations were rarely detected in the absence of established drug resistance mutations in ART-exposed individuals (prevalence, <1%). None of the 5 connection domain mutations associated with treatment showed a statistically significant effect on response to cART.Conclusions.Despite their frequent emergence, connection domain mutations did not show large detrimental effects on response to cART. Currently, routine implementation of connection domain sequencing seems unnecessary for developed health care settings.
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影响因子：
1.2
作者：
H. Price;D. Asboe;A. Pozniak;B. Gazzard;E. Fearnhill;D. Pillay;D. Dunn
通讯作者：
D. Dunn
影响因子：
5.4
作者：
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通讯作者：
Perno, Carlo Federico
影响因子：
--
作者：
Von Wyl, Viktor;Yerly, Sabine;Guenthard, Huldrych F.
通讯作者：
Guenthard, Huldrych F.
DART 研究（NORA 子研究）中，在没有病毒载量监测的情况下，非 B 亚型中逆转录酶 (RT) N348I 突变的患病率和体外特征。
DOI：
--
发表时间：
2009
期刊：
影响因子：
--
作者：
A. McCormick;A. Burke;P. Katundu;F. Lyagoba;C. Parry;D. Yirrell;P. Munderi;V. Robertson;P. Kaleebu;D. Pillay
通讯作者：
D. Pillay
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影响因子：
2.2
作者：
M. Ehteshami;M. Götte
通讯作者：
M. Götte