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首页> 外文期刊>AIDS Research and Human Retroviruses >High Prevalence of HIV Low Abundance Drug-Resistant Variants in a Treatment-Naive Population in North Rift Kenya
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High Prevalence of HIV Low Abundance Drug-Resistant Variants in a Treatment-Naive Population in North Rift Kenya

机译：肯尼亚北大裂谷无治疗人群中艾滋病毒低丰度耐药性变异株的高患病率

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The advent of antiretroviral treatment (ART) has resulted in a dramatic reduction in AIDS-related morbidity and mortality. However, the emergence and spread of antiretroviral drug resistance (DR) threaten to negatively impact treatment regimens and compromise efforts to control the epidemic. It is recommended that surveillance of drug resistance occur in conjunction with scale-up efforts to ensure that appropriate first-line therapy is offered relative to the resistance that exists. However, standard resistance testing methods used in Sub-Saharan Africa rely on techniques that do not include low abundance DR variants (LADRVs) that have been documented to contribute to treatment failure. The use of next generation sequencing (NGS) has been shown to be more sensitive to LADRVS. We have carried out a preliminary investigation using NGS to determine the prevalence of LDRVS among a drug-naive population in North Rift Kenya. Antiretroviral-naive patients attending a care clinic in North Rift Kenya were requested to provide and with consent provided blood samples for DR analysis. DNA was extracted and amplified and nested PCR was conducted on the pol RT region using primers tagged with multiplex identifiers (MID). Resulting PCR amplicons were purified, quantified, and pyrosequenced using a GS FLX Titanium PicoTiterPlate (Roche). Valid pyrosequencing reads were aligned with HXB-2 and the frequency and distribution of nucleotide and amino acid changes were determined using an in-house Perl script. DR mutations were identified using the IAS-USA HIV DR mutation database. Sixty samples were successfully sequenced of which 26 were subtype A, 9 were subtype D, 2 were subtype C, and the remaining were recombinants. Forty-six (76.6%) had at least one drug resistance mutation, with 25 (41.6%) indicated as major and the remaining 21 (35%) indicated as minor. The most prevalent mutation was NRTI position K219Q/R (11/46, 24%) followed by NRTI M184V (5/46, 11%) and NNRTI K103N (4/46, 9%). Our use of NGS technology revealed a high prevalence of LADRVs among drug-naive populations in Kenya, a region with predominantly non-B subtypes. The impact of these mutations on the clinical outcome of ART can be ascertained only through long-term follow-up.
机译：抗逆转录病毒治疗（ART）的出现大大降低了与AIDS有关的发病率和死亡率。但是，抗逆转录病毒药物耐药性（DR）的出现和扩散可能会对治疗方案产生负面影响，并损害控制该流行病的努力。建议对耐药性进行监测，同时加大力度，以确保相对于现有耐药性提供适当的一线治疗。但是，在撒哈拉以南非洲使用的标准抗药性测试方法所依赖的技术不包括已证明会导致治疗失败的低丰度DR变异体（LADRV）。事实证明，使用下一代测序（NGS）对LADRVS更敏感。我们已经使用NGS进行了初步调查，以确定在肯尼亚北纵谷的一名纯毒品人群中LDRVS的患病率。要求在肯尼亚北纵谷的一家护理诊所就诊的未接受过抗逆转录病毒治疗的患者提供并经同意提供血样用于DR分析。提取DNA并进行扩增，并使用标记有多重标识符（MID）的引物在pol RT区域进行巢式PCR。使用GS FLX Titanium PicoTiterPlate（Roche）对得到的PCR扩增子进行纯化，定量和焦磷酸测序。将有效的焦磷酸测序读数与HXB-2进行比对，并使用内部Perl脚本确定核苷酸和氨基酸变化的频率和分布。使用IAS-USA HIV DR突变数据库鉴定DR突变。成功测序了60个样品，其中26个是A型，9个是D型，2个是C型，其余为重组体。四十六（76.6％）具有至少一个耐药突变，其中25（41.6％）表示为重大，其余21（35％）表示为次要。最普遍的突变是NRTI位置K219Q / R（11/46，24％），其次是NRTI M184V（5/46，11％）和NNRTI K103N（4/46，9％）。我们使用NGS技术揭示了肯尼亚非毒品人群中LADRV的高患病率，该地区主要为非B型亚型。这些突变对ART临床结果的影响只能通过长期随访来确定。

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