High prevalence of antiretroviral resistance in treated Ugandans infected with non-subtype B human immunodeficiency virus type 1

High prevalence of antiretroviral resistance in treated Ugandans infected with non-subtype B human immunodeficiency virus type 1
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DOI:
10.1089/088922204323048104
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发表时间:
2004-04-01
影响因子:
1.5
通讯作者:
Arts, EJ
Arts, EJ
中科院分区:
医学4区
文献类型:
--
作者:
Richard, N;Juntilla, M;Arts, EJ

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这项研究检查了感染 1 型人类免疫缺陷病毒 (HIV-1) 的乌干达人中逆转录酶和蛋白酶编码区耐药突变的出现和流行情况:接受抗逆转录病毒药物 (ARV) 治疗。对分别纳入横断面和纵向观察队列的 50 名和 16 名参与者进行了基因型耐药性测试。 113 个 HIV-1 PR-RT 序列中的大多数被归类为 A 和 D 亚型。耐药突变在 52% 经历过 ARV 的个体中普遍存在,27 个 ARV 耐药菌株中有 17 个在逆转录酶中具有 3 个或更多突变。蛋白酶的抗性突变不太常见,但 50 名患者中只有 17 名在样本采集时接受了蛋白酶抑制剂治疗。纵向队列中 16 名参与者中的 3 名也选择了赋予耐药性的突变,即开始抗逆转录病毒治疗后不到 8 个月。抗逆转录病毒药物耐药性的迅速出现与治疗方案的依从性差有关,而这又与治疗费用有关。然而,HIV-1 D 亚型(33 人中的 21 人)的 ARV 耐药率确实略高于 A 亚型(25 人中的 7 人)感染者。总体而言,这项观察性研究表明,在乌干达和其他可能的发展中国家接受抗逆转录病毒治疗的个体中,抗逆转录病毒药物 HIV-1 分离株正在迅速出现。
This study examined the emergence and prevalence of drug-resistant mutations in reverse transcriptase and protease coding regions in human immunodeficiency virus type 1 (HIV-1)-infected Ugandans: treated with antiretroviral drugs (ARV). Genotypic resistance testing was performed on 50 and 16 participants who were enrolled in a cross-sectional and longitudinal observational cohort, respectively. The majority of the 113 HIV-1 PR-RT sequences were classified as subtypes A and D. Drug resistance mutations were prevalent in 52% of ARV-experienced individuals, and 17 of 27 ARV-resistant isolates had three mutations or more in reverse transcriptase. Resistance mutations in protease were less prevalent but only 17 of the 50 patients were receiving a protease inhibitor upon sample collection. Mutations conferring drug resistance were also selected in 3 of 16 participants in the longitudinal cohort, i.e., less than 8 months after the initiation of ARV treatment. Rapid emergence of ARV resistance was associated with poor adherence to treatment regimens, which was related to treatment costs. ARV resistance did, however, appear at a slightly higher prevalence in HIV-1 subtype D (21 of 33) than subtype A (7 of 25) infected individuals. Overall, this observational study suggests that ARV-resistant HIV-1 isolates are emerging rapidly in ARV-treated individual in Uganda and possibly other developing countries.