Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
Institute of Medical Virology, Charité Universitätsmedizin Berlin, Berlin, Germany.
PLoS One. 2018 Nov 8;13(11):e0206234. doi: 10.1371/journal.pone.0206234. eCollection 2018.
BACKGROUND: Molecular surveillance of newly diagnosed HIV-infections is important for tracking trends in circulating HIV-variants, including those with transmitted drug resistances (TDR) to sustain ART efficacy. METHODS: Dried serum spots (DSS) are received together with the statutory notification of a new diagnosis. 'Recent infections' (<155 days) classified by a 'recent infection test algorithm' (BED-CEIA and clinical data) are genotyped in HIV-protease (PR), reverse transcriptase (RT) and integrase (INT) to determine the HIV-1 subtype, to calculate prevalence and trends of TDR, to predict baseline susceptibility and to identify potential transmission clusters for resistant variants. RESULTS: Between January 2013 and December 2016, 1,885 recent infections were analysed regarding the PR/RT genomic region, with 43.5% of these also being subjected to the analysis of INT. The proportion of HIV-1 non-B viruses (31.3%; 591/1,885) increased from 21.6% to 36.0%, particularly the subtypes A (5.0% to 8.3%) and C (3.2% to 7.7%; all ptrends < 0.01). The subtype A increment is mainly due to transmissions within men who have sex with men (MSM) while subtype C transmissions are associated with heterosexuals and people who inject drugs. The prevalence of TDR was stable at 11.0% (208/1,885) over the study period. Resistances to nucleotide RT inhibitors (NRTI) and PR inhibitors (PI) were 4.5% and 3.2%, respectively, without identifiable trends. In contrast, resistances to non-NRTIs (NNRTI, 4.7%) doubled between 2014 and 2016 from 3.2% to 6.4% (ptrend = 0.02) mainly due to the K103N mutation (from 1.7% to 4.1%; ptrend = 0.03) predominantly detected in recently infected German MSM not linked to transmission clusters. Transmitted INSTI mutations were present in only one case (T66I) and resistance to dolutegravir was not identified at all. Reduced susceptibility to recommended first-line therapies was low with 1.0% for PIs, 1.3% for NRTIs and 0.7% for INSTIs, but high for the NNRTIs efavirence (4.9%) and rilpivirine (6.0%) due to the K103N mutation and the polymorphic mutation E138A. These trends in therapy-naïve individuals impact current first-line regimens and require awareness and vigilant surveillance.
背景：对新诊断的 HIV 感染进行分子监测对于跟踪循环 HIV 变体的趋势非常重要，包括具有传播耐药性（TDR）的变体，以维持 ART 的疗效。
方法：与法定的新诊断通知一起接收干燥血清斑（DSS）。通过“最近感染测试算法”（BED-CEIA 和临床数据）分类的“近期感染”（<155 天）在 HIV-蛋白酶（PR）、逆转录酶（RT）和整合酶（INT）中进行基因分型，以确定 HIV-1 亚型，计算 TDR 的流行率和趋势，预测基线敏感性，并识别具有耐药变异的潜在传播簇。
结果：2013 年 1 月至 2016 年 12 月，对 1885 例近期感染的 PR/RT 基因组区域进行了分析，其中 43.5%的样本还进行了 INT 分析。非 B 型 HIV-1 病毒（31.3%；591/1885）的比例从 21.6%增加到 36.0%，特别是亚型 A（5.0%至 8.3%）和 C（3.2%至 7.7%；所有ptrends < 0.01）。A 亚型的增加主要是由于男男性行为者（MSM）内的传播，而 C 亚型的传播与异性恋者和注射毒品者有关。研究期间，TDR 的流行率稳定在 11.0%（208/1885）。核苷酸 RT 抑制剂（NRTI）和 PR 抑制剂（PI）的耐药性分别为 4.5%和 3.2%，无明显趋势。相比之下，非核苷类逆转录酶抑制剂（NNRTI，4.7%）的耐药性在 2014 年至 2016 年间翻了一番，从 3.2%增加到 6.4%（ptrend = 0.02），主要是由于 K103N 突变（从 1.7%增加到 4.1%；ptrend = 0.03）主要发生在未与传播簇相关联的最近感染的德国 MSM 中。仅在一例中发现了传播的 INSTI 突变（T66I），并且根本没有发现对多替拉韦的耐药性。对推荐的一线治疗方案的敏感性降低，PI 为 1.0%，NRTI 为 1.3%，INSTI 为 0.7%，但 NNRTI 中的依非韦伦（4.9%）和利匹韦林（6.0%）的耐药性较高，因为 K103N 突变和多态性突变 E138A。这些初治个体的趋势影响当前的一线治疗方案，需要了解并进行警惕监测。
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