We investigated transmission dynamics of a large HIV outbreak among persons who inject drugs (PWID) in Kentucky and Ohio during 2017–2020 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase (pol) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02_AG (2.5 per cent) and CRF02_AG-like (21.8 per cent); and many unique recombinant forms (URFs) composed of CRFs with major subtypes and sub-subtypes (CRF02_AG/B (24.3 per cent), B/CRF02_AG/B (0.5 per cent), and A6/D/B (6.4 per cent)). Cluster analysis of sequences using a 1.5 per cent genetic distance identified 13 clusters, including a 75-member cluster composed of CRF02_AG-like and CRF02_AG/B, an 18-member CRF02_AG/B cluster, subtype B clusters of sizes ranging from two to 23, and a 9-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02_AG/B variants with 10 unique breakpoints likely originating from subtype B and CRF02_AG-like viruses in the largest clusters. The addition of contact tracing results from Ohio to the genetic networks identified linkage between persons with subtype B, CRF02_AG, and CRF02_AG/B sequences in the clusters supporting de novo recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02_AG; B and CRF02_AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017–2018 in certain other molecular clusters. This outbreak among PWID in Kentucky and Ohio was likely driven by rapid transmission of multiple HIV-1 variants including de novo viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread.

中文翻译：

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美国肯塔基州和俄亥俄州注射吸毒者大规模爆发的艾滋病病毒多样性、重组和重复感染

我们通过使用详细的系统发育、网络、重组和聚类定年分析，调查了 2017 年至 2020 年肯塔基州和俄亥俄州注射吸毒者 (PWID) 中大规模艾滋病毒爆发的传播动态。使用来自与调查相关的 193 人的聚合酶 (pol) 序列，我们记录了 HIV-1 的高度多样性，包括 B 亚型（44.6%）；多种循环重组形式 (CRF)，包括 CRF02_AG (2.5%) 和 CRF02_AG 样 (21.8%)；以及许多由具有主要亚型和亚亚型的 CRF 组成的独特重组形式 (URF)（CRF02_AG/B（24.3%）、B/CRF02_AG/B（0.5%）和 A6/D/B（6.4%） ）。使用 1.5% 遗传距离对序列进行聚类分析，确定了 13 个簇，包括由 CRF02_AG 样和 CRF02_AG/B 组成的 75 成员簇、18 成员 CRF02_AG/B 簇、大小从 2 到 23 不等的 B 亚型簇，以及一个 9 成员 A6/D 和 A6/D/B 集群。重组和系统发育分析确定了具有 10 个独特断点的 CRF02_AG/B 变体，可能源自最大簇中的 B 亚型和 CRF02_AG 样病毒。将俄亥俄州的接触者追踪结果添加到遗传网络中，确定了支持从头重组生成的簇中具有 B 亚型、CRF02_AG 和 CRF02_AG/B 序列的人之间的联系。具有多个样本的人的重复感染率为 13.3% (8/60)，包括 B 和 CRF02_AG 感染；B和CRF02_AG/B；或 B 和 A6/D/B。除了与此次疫情相关的多个不同分子簇的存在之外，簇测年推断与最大分子簇相关的传播早在 2006 年就发生了，2017 年至 2018 年期间某些其他分子簇的传播率很高。肯塔基州和俄亥俄州吸毒者中的这次疫情爆发可能是由多种 HIV-1 变体的快速传播造成的，其中包括来自社区内循环病毒的从头病毒重组体。我们的研究结果记录了 HIV-1 的高传播率以及通过合作伙伴服务和分子集群进行的聚类，强调了利用多种不同数据源和分析（包括来自疾病干预专家调查的数据）的重要性，以更好地了解疫情动态并阻止 HIV 传播。