A phylotype-based analysis highlights the role of drug-naive HIV-positive individuals in the transmission of antiretroviral resistance in the UK
A phylotype-based analysis highlights the role of drug-naive HIV-positive individuals in the transmission of antiretroviral resistance in the UK
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DOI：
10.1097/qad.0000000000000768
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发表时间：
2015-09-24
期刊：
影响因子：
3.8
通讯作者：
Hue, Stephane
中科院分区：
文献类型：
--
作者：
Mourad, Raphael;Chevennet, Francois;Hue, Stephane
目的：抗逆转录病毒初治HIV阳性个体有助于耐药病毒的传播，影响一线治疗。使用系统发育推断，我们量化的比例传播的耐药性起源于一个治疗幼稚source.Methods：使用一种新的基于基因型的方法，24550 HIV-1亚型B部分pol基因序列从英国HIV耐药性数据库进行了分析。HIV阳性个体中耐药性的持续传播被确定为至少三个序列的重复类型，至少有一个共享的耐药性突变，最大进化枝内遗传距离为4.0%，基底分支支持率至少为90%。使用快速最小二乘分子时钟推断approach.Results：大约70%的传播耐药的传播链的持续时间估计有一个治疗幼稚的来源。最常传播的突变是蛋白酶基因的L90 M和逆转录酶基因的K103 N、T215 D和T215 S。回复到野生型发生在一个低频率和药物独立的水库的阻力已经持续了长达13 years.Conclusion：这些结果说明了病毒健身的影响，建立耐药水库和支持的概念，早期诊断和治疗艾滋病毒感染是必要的，以抵消抗逆转录病毒耐药性的传播。基于系统发育的推断是一种有吸引力的方法，用于常规监测HIV以及其他有基因型耐药数据的病原体的耐药性。
Objective:Antiretroviral-naive HIV-positive individuals contribute to the transmission of drug-resistant viruses, compromising first-line therapy. Using phylogenetic inference, we quantified the proportion of transmitted drug-resistance originating from a treatment-naive source.Methods:Using a novel phylotype-based approach, 24550 HIV-1 subtype B partial pol gene sequences from the UK HIV Drug Resistance database were analysed. Ongoing transmission of drug resistance amongst HIV-positive individuals was identified as phylotypes of at least three sequences with at least one shared drug resistance mutation, a maximum intra-clade genetic distance of 4.0% and a basal branch support at least 90%. The time of persistence of the transmission chains was estimated using a fast least-squares molecular clock inference approach.Results:Around 70% of transmitted drug-resistance had a treatment-naive source. The most commonly transmitted mutations were L90M in the protease gene and K103N, T215D and T215S in reverse transcriptase. Reversion to wild type occurred at a low frequency and drug-independent reservoirs of resistance have persisted for up to 13 years.Conclusion:These results illustrate the impact of viral fitness on the establishment of resistance reservoirs and support the notion that earlier diagnoses and treatment of HIV infections are warranted for counteracting the spread of antiretroviral resistance. Phylotype-based phylogenetic inference is an attractive approach for the routine surveillance of transmitted drug resistance in HIV as well as in other pathogens for which genotypic resistance data are available.