Transmission networks of drug resistance acquired in primary/early stage HIV infection.
Transmission networks of drug resistance acquired in primary/early stage HIV infection.
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DOI：
10.1097/qad.0b013e3283121c90
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发表时间：
2008-11-30
期刊：
影响因子：
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通讯作者：
Montreal PHI Cohort and HIV Prevention Study Groups
中科院分区：
文献类型：
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作者：
Brenner BG;Roger M;Moisi DD;Oliveira M;Hardy I;Turgel R;Charest H;Routy JP;Wainberg MA;Montreal PHI Cohort and HIV Prevention Study Groups
基于人群的原发/近期艾滋病毒感染（PHI）的测序可以为了解当地流行病的传播动态提供一个框架。在魁北克，一半的PHI代表聚集性传播事件。这项研究确定了聚集性对耐药性向前传播的累积影响。HIV-1 pol序列数据集可用于所有基因分型的PHI（血清转换后<6个月（n=848亚型B感染，1997-2007））。系统发育分析建立了聚集的传播事件，基于具有高自举值（>98%）和短遗传距离的最大似然拓扑。确定了对核苷类和非核苷类逆转录酶抑制剂（NRTI和NNRTI）和蛋白酶抑制剂（PI）的耐药在独特传播和聚集传播中的分布。1997-2008年，在半数近期/早期感染病例中观察到了发作性聚集。总体而言，29%和28%的新感染分为小（<5个PHI/簇，n=242/848）和大传播链（≥5个PHI/簇，n=239/848），平均分别为2.8 ± 0.1个PHI/簇和10.3 ± 1.0个PHI/簇。核苷类似物突变和215种耐药变异（T215 C/D/I/F/N/S/Y）的传播随聚集性下降（独特、小和大聚集性传播分别为7.9% vs. 3.4% vs. 1.2%和5.8% vs. 1.7% vs. 1.1%）。相反，聚集性与携带NNRTI耐药病毒的传播增加相关（分别为6.6% vs. 6.0% vs. 15.5%）。早期/PHI阶段感染的聚集性对不同药物类别的耐药性传播的影响不同。针对公共卫生、预防和诊断战略，为遏制耐药性传播提供了一个独特的机会。
Population-based sequencing of primary/recent HIV infections (PHI) can provide a framework for understanding transmission dynamics of local epidemics. In Quebec, half of PHI represent clustered transmission events. This study ascertained the cumulative implications of clustering on onward transmission of drug resistance. HIV-1 pol sequence datasets were available for all genotyped PHI (<6 months post-seroconversion (n=848 subtype B infections, 1997-2007). Phylogenetic analysis established clustered transmission events, based on maximum likelihood topologies having high bootstrap values (>98%) and short genetic distances. The distributions of resistance to nucleoside and non-nucleoside RT inhibitors (NRTIs and NNRTIs) and protease inhibitors (PIs) in unique and clustered transmissions were ascertained. Episodic clustering was observed in half of recent/early stage infections from 1997-2008. Overall, 29% and 28% of new infections segregated into small (<5 PHI/cluster, n=242/848) and large transmission chains (≥5 PHI/cluster, n=239/848), averaging 2.8 ± 0.1 PHI/cluster and 10.3 ± 1.0 PHI/cluster, respectively. The transmission of nucleoside analogue mutations and 215 resistant variants (T215C/D/I/F/N/S/Y) declined with clustering (7.9% vs. 3.4% vs. 1.2% and 5.8% vs. 1.7% vs. 1.1% for unique, small and large clustered transmissions, respectively). In contrast, clustering was associated with the increased transmission of viruses harbouring resistance to NNRTIs (6.6% vs. 6.0% vs. 15.5%, respectively). Clustering in early/PHI stage infection differentially affects transmission of drug resistance to different drug classes. Public health, prevention and diagnostic strategies, targeting PHI, afford a unique opportunity to curb the spread of transmitted drug resistance.