Lai Alessia, Simonetti Francesco Roberto, Brindicci Gaetano, Bergna Annalisa, Di Giambenedetto Simona, Sterrantino Gaetana, Mussini Cristina, Menzo Stefano, Bagnarelli Patrizia, Zazzi Maurizio, Angarano Gioacchino, Galli Massimo, Monno Laura, Balotta Claudia
Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Microbiol. 2019 Apr 12;10:769. doi: 10.3389/fmicb.2019.00769. eCollection 2019.
The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18-37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy.
意大利HIV-1的分子流行病学正变得日益复杂，主要是由于非B亚型的传播以及新重组形式的出现。我们之前对首例意大利流行重组形式（CRF60_BC）的暴发进行了特征描述，该暴发于2009年至2011年间发生在居住于普利亚大区的年轻男男性行为者中。在此，我们展示了一项为期5年的随访监测，以追踪CRF60_BC的演变，并调查其在意大利的进一步传播情况。我们从巴里大学传染病诊所登记的携带CRF60_BC的患者中收集了额外的序列和临床数据。除了之前鉴定的24个序列外，我们还从居住在普利亚大区的患者中检索到27个CRF60_BC序列，这些患者的流行病学和临床特征与最初的暴发情况无异，即意大利血统、HIV诊断时年龄较轻（中位数：24岁；范围：18 - 37岁）、男男性行为者风险因素（23/25，92%）以及近期感染（2008年至2017年）。序列分析显示总体核苷酸多样性不断增加，随着时间推移仅有少数核苷酸变化固定下来。在意大利各地检测到另外27个序列，分布在多个遥远地区。通过BLAST搜索，我们还鉴定出2013年在英国分离出的一个CRF60_BC序列。三名患者携带一种独特的第二代重组形式，其中CRF60_BC是亲本菌株之一。我们的数据表明，CRF60_BC已具有流行病学重要性，在意大利多个地区的年轻男男性行为者中传播，并在几年内增加了其种群规模，因为自我们首次报告以来，迄今鉴定出的序列数量已增至三倍。观察到的CRF60_BC进一步分化可能是由于传播链中的进化瓶颈和宿主适应性。值得注意的是，我们检测到三个第二代重组体，进一步支持了CRF60_BC的广泛传播以及意大利HIV-1疫情日益增加的复杂性。
