title: Epidemiological network analysis in HIV-1 B infected patients diagnosed in Italy between 2000 and 2008.
abstract: This study, through a phylogenetic analysis, is aimed to identify potential epidemiological networks and sequence interrelationships between acute/early and chronic infections in both drug-naïve and drug-experienced individuals within a local, well-defined setting and to investigate the population dynamics of transmitted resistance and the potential contribution of untreated patients to the spread of antiretroviral resistance. A total of 884 HIV-1 B subtype pol gene sequences from 306 drug-naïve (40 recently and 266 chronically infected) and 578 drug-treated HIV-1 infected patients were collected through routine drug-resistance testing between 2000 and 2008 in a single center (Division of Infectious Disease, Bergamo, Northern Italy). Bayesian phylogenetic tree was reconstructed and transmission clusters were recognized using a posterior probability as statistical support of each cluster. Differences among clustered and non-clustered drug-resistance mutations were assessed by Fisher's exact test. In our cohort we identified five clusters including ≥6 sequences with the root posterior probability of 100%. Dated phylogenies reconstructed through Bayesian Markov chain Monte Carlo model was possible for only two main clade (≥10 sequences) originated between 1990 and 2002. Among the 306 drug-naïve individuals, 12% carried a viral strain with at least 1 major mutation associated with transmitted drug resistance and 36% of these strains were involved in significant clusters. We report for the first time that many (34%) of HIV-1 subtype B transmission clusters identified in Italy were only composed by drug-naïve individuals and that the 14% of transmitted drug resistance was linked to transmission clusters composed only of newly diagnosed individuals. The phylogenetic analysis was performed on a large cohort of drug-naïve recently/chronically infected individuals where drug-experienced patients represent almost all infected individuals in a restricted geographical area. Our findings highlight the role of newly diagnosed individuals, not yet exposed to antiretroviral drugs, in the transmission of drug-resistant HIV-1 strains, providing new insights for the planning and management of treatment programs in developing countries.
authors.affiliation: Microbiology and Virology, Ospedali Riuniti di Bergamo, Italy.
authors.forename: Annapaola
authors.initials: A
authors.lastname: Callegaro
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.forename: Claudia
authors.initials: C
authors.lastname: Alteri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lo Presti
authors.forename: Daniela
authors.initials: D
authors.lastname: Valenti
authors.forename: Antonio
authors.initials: A
authors.lastname: Goglio
authors.forename: Marco
authors.initials: M
authors.lastname: Salemi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cella
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
authors.forename: Franco
authors.initials: F
authors.lastname: Maggiolo
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001499:Bayes Theorem; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D017423:Sequence Analysis, RNA