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

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. Aim: 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.