Brenner Bluma G, Roger Michel, Moisi Daniela D, Oliveira Maureen, Hardy Isabelle, Turgel Reuven, Charest Hugues, Routy Jean-Pierre, Wainberg Mark A
McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
AIDS. 2008 Nov 30;22(18):2509-15. doi: 10.1097/QAD.0b013e3283121c90.
Population-based sequencing of primary/recent HIV infections (PHIs) can provide a framework for understanding transmission dynamics of local epidemics. In Quebec, half of PHIs 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 postseroconversion; 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 nonnucleoside reverse transcriptase inhibitors and protease inhibitors 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 (> or =5 PHI/cluster, n = 239/848), averaging 2.8 +/- 0.1 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 nonnucleoside reverse transcriptase inhibitors (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.
基于人群的原发性/近期HIV感染（PHI）测序可为理解当地疫情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。本研究确定了聚集性对耐药性传播的累积影响。
可获得所有基因分型的PHI（血清转化后<6个月；n = 848例B亚型感染，1997 - 2007年）的HIV-1 pol序列数据集。系统发育分析基于具有高自展值（>98%）和短遗传距离的最大似然拓扑结构确定聚集性传播事件。确定了独特传播和聚集性传播中对核苷和非核苷逆转录酶抑制剂以及蛋白酶抑制剂耐药性的分布。
在1997 - 2008年的一半近期/早期感染中观察到间歇性聚集。总体而言，29%和28%的新感染分别分为小的（<5例PHI/簇，n = 242/848）和大的传播链（≥5例PHI/簇，n = 239/848），平均每簇分别为2.8±0.1例和10.3±1.0例PHI。核苷类似物突变和215种耐药变异（T215C/D/I/F/N/S/Y）的传播随着聚集性而下降（独特传播、小聚集性传播和大聚集性传播分别为7.9%对3.4%对1.2%以及5.8%对1.7%对1.1%）。相比之下，聚集性与对非核苷逆转录酶抑制剂耐药的病毒传播增加相关（分别为6.6%对6.0%对15.5%）。
早期/PHI阶段感染中的聚集性对不同药物类别的耐药性传播有不同影响。针对PHI的公共卫生、预防和诊断策略提供了一个遏制传播性耐药性传播的独特机会。
