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坦桑尼亚达累斯萨拉姆初治感染多种HIV-1亚型和重组形式的青年对抗逆转录病毒药物的基因型耐药率

Prevalence of genotypic resistance to antiretroviral drugs in treatment-naive youths infected with diverse HIV type 1 subtypes and recombinant forms in Dar es Salaam, Tanzania.

作者信息

Mosha F, Urassa W, Aboud S, Lyamuya E, Sandstrom E, Bredell H, Williamson C

机构信息

Field Epidemiology and Laboratory Training Programme, Ministry of Health and Social Welfare , Dar es Salaam, Tanzania.

出版信息

AIDS Res Hum Retroviruses. 2011 Apr;27(4):377-82. doi: 10.1089/aid.2010.0113. Epub 2010 Oct 18.

Abstract

As human immunodeficiency virus (HIV) diversity may have an impact on both vaccine efficacy and drug resistance, it is important to have knowledge of circulating genetic variants. With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. This study aimed to determine the circulating HIV subtypes and recombinant forms, as well as the prevalence of ARV drug resistance mutations, among 75 treatment-naive HIV-infected youths in Dar es Salaam, Tanzania. Gag (n = 48), partial pol (n = 44), and partial env (n = 35) sequencing was performed; all three regions were sequenced in 26 samples. Evidence of infection with recombinant viruses was found in 12 (46%) participants; AC recombinants were the most commonly detected and they were identified in six (23%) participants. Of individuals infected with nonrecombinant strains, subtype A was most commonly detected in seven (27%) participants, followed by subtype C detected in six (23%) participants and subtype D detected in one (4%) participant. Among the pol sequences from 44 individuals, three (7%) had resistance to nucleoside reverse transcriptase (RT) inhibitors and four (9%) had nonnucleoside RT inhibitor resistance mutations. Of these, three (7%) individuals were infected with viruses with cross-resistance mutations to both classes of RT inhibitors. These resistant mutations were all associated with drugs currently used in first-line therapy and in the prevention of vertical transmission. This high prevalence of resistance mutations is of considerable concern in apparently drug-naive populations as it may result in treatment failure and the spread of ARV-resistant strains.

摘要

由于人类免疫缺陷病毒(HIV)的多样性可能会对疫苗效力和耐药性产生影响,因此了解流行的基因变异非常重要。随着抗逆转录病毒(ARV)药物在非洲的广泛使用,一个主要的潜在挑战是出现对ARV耐药的HIV毒株的风险。本研究旨在确定坦桑尼亚达累斯萨拉姆75名未接受过治疗的HIV感染青年中流行的HIV亚型和重组形式,以及ARV耐药突变的流行情况。对gag(n = 48)、部分pol(n = 44)和部分env(n = 35)进行了测序;26个样本对所有三个区域都进行了测序。在12名(46%)参与者中发现了感染重组病毒的证据;AC重组体是最常检测到的,在6名(23%)参与者中被鉴定出来。在感染非重组毒株的个体中,最常检测到的是A亚型,有7名(27%)参与者,其次是C亚型,有6名(23%)参与者,D亚型有1名(4%)参与者。在44名个体的pol序列中,3名(7%)对核苷类逆转录酶(RT)抑制剂有耐药性,4名(9%)有非核苷类RT抑制剂耐药突变。其中,3名(7%)个体感染了对两类RT抑制剂都有交叉耐药突变的病毒。这些耐药突变都与目前一线治疗和预防垂直传播中使用的药物有关。在明显未接触过药物的人群中,这种高耐药突变率令人相当担忧,因为这可能导致治疗失败和ARV耐药毒株的传播。

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