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HIV type 1 subtype C drug resistance among pediatric and adult South African patients failing antiretroviral therapy.

机译:在抗逆转录病毒治疗失败的小儿和成年南非患者中,HIV 1型C型亚型耐药。

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摘要

The emergence of HIV drug resistance is a major obstacle to effective antiretroviral (ARV) treatments. This study examined the drug resistance profiles among South African patients virologically failing ARV therapies between 2000 and 2003, prior to the introduction of a national treatment program. Samples were obtained from 65 HIV-1 subtype C-infected patients (39 children and 26 adults) who had received at least two nucleoside reverse transcriptase inhibitors (NRTIs) and either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Resistance assays were performed using the HIV-1 ViroSeq Genotyping System and mutations were defined according to the Stanford Sequence Resistance Database. Ninety-one percent of patients harbored resistance mutations; the most frequent NRTI mutations were M184V/I (37%), D67N (32%), T215Y/F (25%), K70R (21%), M41L (20%), K219Q/E (14%), and K65R (14%), reflecting the frequent use of lamuvidine and zidovudine. K103N (25%), V106M (20%), and G190A (17%) were found among patients failing nevirapine- or efavirenz-containing regimens. Of the patients who received PIs, the most common mutations were V82A/T (12%), M46I (11%), and L90M (8%). Mutations were similar among adults and children. These data indicate that HIV-1 drug resistance develops in South African subtype C-infected patients failing ARV therapy with mutations comparable to those found among patients infected with subtype B viruses.
机译:HIV耐药性的出现是有效抗逆转录病毒(ARV)治疗的主要障碍。这项研究在引入国家治疗计划之前,研究了2000年至2003年间在病毒学上抗病毒ARV疗法无效的南非患者的耐药情况。样本是从65例接受HIV-1亚型C感染的患者(39名儿童和26名成人)中获得的,这些患者已接受至少两种核苷类逆转录酶抑制剂(NRTIs)和一种非核苷类逆转录酶抑制剂(NNRTI)或蛋白酶抑制剂(PI)。使用HIV-1 ViroSeq基因分型系统进行抗性测定,并根据斯坦福序列抗性数据库定义突变。百分之九十一的患者具有耐药性突变。最常见的NRTI突变是M184V / I(37%),D67N(32%),T215Y / F(25%),K70R(21%),M41L(20%),K219Q / E(14%)和K65R (14%),反映了拉米替丁和齐多夫定的频繁使用。在含奈韦拉平或依非韦伦治疗方案失败的患者中发现了K103N(25%),V106M(20%)和G190A(17%)。在接受PI的患者中,最常见的突变是V82A / T(12%),M46I(11%)和L90M(8%)。成人和儿童之间的突变相似。这些数据表明,在接受ARV治疗失败的南非C型亚型感染患者中,HIV-1耐药性发生了突变,突变程度与感染B型亚型病毒的患者相当。

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