Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.

Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.
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DOI:
10.1097/qai.0b013e3181b06125
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发表时间:
2009-10-01
期刊:
Journal of acquired immune deficiency syndromes (1999)
影响因子:
--
通讯作者:
APIN Plus/Harvard PEPFAR Team
APIN Plus/Harvard PEPFAR Team
中科院分区:
其他
文献类型:
--
作者:
Hawkins CA;Chaplin B;Idoko J;Ekong E;Adewole I;Gashau W;Murphy RL;Kanki P;APIN Plus/Harvard PEPFAR Team

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非洲国家的艾滋病毒-1流行很大程度上是由于非B型艾滋病毒-1亚型。在这些国家观察到的抗逆转录病毒耐药性突变的模式和频率可能与发达国家不同,在发达国家,艾滋病毒-1 B亚型占主导地位。对一线治疗(血浆HIVRNA和GT;1000拷贝/毫升)治疗失败的尼日利亚患者进行了HIV-1亚型和耐药性突变检测。RT和PR基因的序列分析显示了耐药突变和HIV-1病毒亚型。K65R突变患者的特定突变模式和临床特征被描述。自2005年以来,对338名患者进行了评估。最常见的亚型是CRF02_AG[152/338(44.9%)]和G[128/338(37.9%)]。307/338(90.8%)患者既往曾接受司他夫定和/或齐多夫定+拉米夫定+法韦伦或奈韦拉平治疗,41/338(12.1%)患者曾接受替诺福韦治疗。最常见的NRTI突变是M184V(301例,89.1%)和K70R(91例,26.9%)。338例患者中有37例(10.9%)存在K65R突变。在未接受替诺福韦治疗的K65R患者中,Q151M(p<0.05)、K219R和T69del(p<0.01)突变更为常见。K65R突变被越来越多地认识到,在非B型艾滋病毒亚型患者中,无论他们是否接触过TDF,K65R突变都是一个具有挑战性的发现。
The HIV-1 epidemic in African countries is largely due to non-B HIV-1 subtypes. Patterns and frequency of antiretroviral drug resistance mutations observed in these countries may differ from those in the developed world, where HIV-1 subtype B predominates. HIV-1 subtype and drug resistance mutations were assayed among Nigerian patients with treatment failure on first line therapy (plasma HIV RNA >1000 copies/ml). Sequence analysis of the RT and PR gene revealed drug resistance mutations and HIV-1 viral subtype. Specific patterns of mutations and clinical characteristics are described in patients with the K65R mutation. Since 2005, 338 patients were evaluated. The most prevalent subtypes were CRF02_AG [152/338 (44.9%)] and G [128/338 (37.9%)]. 307/338 (90.8%) patients had previously received stavudine and/or zidovudine + lamivudine + efavirenz or nevirapine; 41/338 (12.1%) had received tenofovir. The most common NRTI mutations observed were M184V (301, 89.1%) and K70R (91, 26.9%). The K65R mutation was present in 37/338 (10.9%) patients. The Q151M (p<0.05), K219R and T69del (p<0.01) mutations were more common in patients with K65R who had not received tenofovir. The K65R mutation is increasingly recognized and is a challenging finding among patients with non-B HIV subtypes whether or not they have been exposed to TDF.