title: HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users.
abstract: BACKGROUND
  Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype.
  
  
  OBJECTIVE
  Aim of this study was to investigate the circulation of A1 subtype in Italy and trace its origin and diffusion through phylogenetic and phylodynamic approaches.
  
  
  RESULTS
  The phylogenetic analysis of 113 A1 pol sequences included in the Italian ARCA database, indicated that 71 patients (62.8%) clustered within 5 clades. A higher probability to be detected in clusters was found for patients from Eastern Europe and Italy (88.9% and 60.4%, respectively) compared to those from Africa (20%) (p < .001). Higher proportions of clustering sequences were found in intravenous drug users with respect to heterosexuals (85.7% vs. 59.3%, p = .056) and in women with respect to men (81.4% vs. 53.2%, p < .006). Subtype A1 dated phylogeny indicated an East African origin around 1961. Phylogeographical reconstruction highlighted 3 significant groups. One involved East European and some Italian variants, the second encompassed some Italian and African strains, the latter included the majority of viruses carried by African and Italian subjects and all viral sequences from Albania and Greece.
  
  
  CONCLUSIONS
  Subtype A1 originated in Central Africa and spread among East European countries in 1982. It entered Italy through three introduction events: directly from East Africa, from Albania and Greece, and from the area encompassing Moldavia and Ukraine. As in previously documented A1 epidemics of East European countries, HIV-1 A1 subtype spread in Italy in part through intravenous drug users. However, Eastern European women contributed to the penetration of such variant, probably through sex work.
authors.affiliation: Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, 'L. Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lai
authors.affiliation: Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, 'L. Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bozzi
authors.affiliation: Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, 'L. Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Franzetti
authors.affiliation: Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, 'L. Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Binda
authors.affiliation: Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, 'L. Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Francesco R
authors.initials: FR
authors.lastname: Simonetti
authors.affiliation: Division of Infectious Diseases, Siena University Hospital, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Laboratory of Microbiology, 'L. Sacco' Hospital, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Micheli
authors.affiliation: 2nd Division of Infectious Diseases, 'L. Sacco' Hospital, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Meraviglia
authors.affiliation: Department of Biomedical Science, Section of Microbiology, Laboratory of Virology, University Politecnica delle Marche, Ancona, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bagnarelli
authors.affiliation: Infectious Diseases Clinic, San Martino Hospital, Genoa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.affiliation: Division of Infectious Disease, University of Bari, Bari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Monno
authors.affiliation: Department of Medical Biotechnology, University of Siena, Siena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Saladini
authors.affiliation: Department of Medical Biotechnology, University of Siena, Siena, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
authors.affiliation: Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, 'L. Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Gianguglielmo
authors.initials: G
authors.lastname: Zehender
authors.affiliation: Epidemiology Unit, Department of Infectious, Parasite and Immune-Mediated Diseases, Italian Institute of Health, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
authors.affiliation: Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, 'L. Sacco' Hospital, University of Milan, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Balotta
mesh_terms: D000328:Adult; D000349:Africa / Q000453:epidemiology; D001499:Bayes Theorem; D055030:Drug Users / Q000706:statistics & numerical data*; D005061:Europe, Eastern / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D058974:Phylogeography; D015819:Substance Abuse, Intravenous / Q000453:epidemiology* / Q000821:virology