K65R with and without S68: A New Resistance Profile in Vivo Detected in Most Patients Failing Abacavir, Didanosine and Stavudine
K65R with and without S68: A New Resistance Profile in Vivo Detected in Most Patients Failing Abacavir, Didanosine and Stavudine
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K65R 联合或不联合 S68：在大多数阿巴卡韦、地达诺辛和司他夫定治疗失败的患者中检测到新的体内耐药情况
DOI：
10.1177/135965350300800212
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发表时间：
2003
影响因子：
1.2
通讯作者：
J. Gerstoft
中科院分区：
文献类型：
--
作者：
B. Røge;T. Katzenstein;N. Obel;H. Nielsen;O. Kirk;C. Pedersen;L. Mathiesen;J. Lundgren;J. Gerstoft
Antiretroviral treatment with three nucleoside reverse transcriptase inhibitors (NRTIs) is widely used, but the combination of abacavir, didanosine and stavudine has never been investigated. We describe the surprising and consistent genotypic and phenotypic outcome in patients failing this combination. As part of a Danish multicentre study, 60 antiretroviral-naive patients were randomized to treatment with abacavir, didanosine and stavudine. Failure was defined as one HIV-1 RNA >400 copies/ml. Genotyping was performed using TrueGene™ HIV-1 assay (Visible Genetics, London, UK). Phenotypic susceptibilities were determined with the Virco Antivirogram assay. Eight patients failed treatment with a median viral load of 2.980 copies/ml (range 478-5.950). At baseline, five patients were wild-type. Three patients harboured nucleoside excision mutations (NEMs), but phenotypic susceptibilities were within normal range. All five patients with wild-type virus developed K65R and four of these patients also acquired the S68G mutation. Phenotypic susceptibility decreased towards abacavir (median 8.9-fold) and didanosine (median 3.2-fold), while susceptibility towards stavudine was unchanged (median 0.8-fold). Susceptibility towards lamivudine and tenofovir decreased median 14.2- and 4.0-fold, respectively. In two patients with baseline resistance mutations, further accumulation of NEMs and V75T or L74V was observed. One patient developed Q151M. Failure of a triple NRTI regimen is possible and frequent with only the K65R mutation. Under adequate selection pressure K65R can easily emerge in vivo and may compromise several future treatment options including newer NRTIs. The unexpected high incidence of S68G suggests a functional role of this mutation in viruses harbouring K65R.
核苷类似物抗性突变K65R和L74V对人类免疫缺陷病毒1型逆转录酶总体突变率和错误特异性的差异影响。
DOI：
10.1074/jbc.m002881200
发表时间：
2000
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shah,FS;Curr,KA;Hamburgh,ME;Parniak,M;Mitsuya,H;Arnez,JG;Prasad,VR
通讯作者：
Prasad,VR
影响因子：
56.9
作者：
Huang, HF;Chopra, R;Harrison, SC
通讯作者：
Harrison, SC