Abstract
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.
Highlights
The human immunodeficiency virus (HIV-1) is a well-known moving target
Due to recombination, when two or more subtypes co-circulate among high risk groups in the same geographical area, unique recombinant forms (URFs) emerge and, if they are detected in at least three epidemiologically unrelated patients, they gain the role of circulating recombinant forms (CRFs) (Robertson et al, 1995)
In addition to the 24 sequences previously described (Monno et al, 2012), we retrieved from local clinical centers, 27 new CRF60_BC sequences from patients residing in Apulia
Summary
The human immunodeficiency virus (HIV-1) is a well-known moving target. HIV-1 high variability and rapid adaptation impose an additional challenge to its diagnosis, treatment, and prevention (Hemelaar, 2013). Due to recombination, when two or more subtypes co-circulate among high risk groups in the same geographical area, unique recombinant forms (URFs) emerge and, if they are detected in at least three epidemiologically unrelated patients, they gain the role of circulating recombinant forms (CRFs) (Robertson et al, 1995). HIV-1 M chimeric forms, URFs and CRFs altogether, are estimated to represent at least 20% of infections globally, with CRF01_AE and CRF02_AG being the most prevalent, accounting for about 13% of all infections (Osmanov et al, 2002). Despite their origin, some CRFs gained epidemiological relevance in previously B subtype-restricted countries with lower HIV-1 prevalence. Multiple new CRFs have been identified in European countries such as Russia (Liitsola et al, 1998; Lukashov et al, 1999; Baryshev et al, 2014), Portugal, Spain (Delgado et al, 2002; Fernandez-Garcia et al, 2016), Italy (Simonetti et al, 2014), United Kingdom (Foster et al, 2014), Luxembourg (Struck et al, 2015), and France (Leoz et al, 2013; Recordon-Pinson et al, 2018)
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