Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy

Abstract

BackgroundIncreased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B-subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy).MethodsPol and V3 sequences were available at the time of diagnosis for all individuals. Maximum-Likelihood and Bayesian phylogenetic-trees with bootstrap and Bayesian-probability supports defined transmission-clusters. HIV-1 drug-resistance and V3-tropism were also evaluated.ResultsAmong 534 new HIV-1 non-B cases, diagnosed from 2011 to 2014, in Central-Italy, 35 carried virus gathering in two distinct clusters, including 27 HIV-1 C and 8 CRF17_BF subtypes, respectively. Both clusters were centralized in Rome, and their origin was estimated to have been after 2007. All individuals within both clusters were males and 37.1% of them had been recently-infected. While C-cluster was entirely composed by Italian men-who-have-sex-with-men, with a median-age of 34 years (IQR:30–39), individuals in CRF17_BF-cluster were older, with a median-age of 51 years (IQR:48–59) and almost all reported sexual-contacts with men and women. All carried R5-tropic viruses, with evidence of atypical or resistance amino-acidic mutations related to NNRTI-drugs (K103Q in C-cluster, and K101E+E138K in CRF17_BF-cluster).ConclusionsThese two epidemiological clusters provided evidence of a strong and recent circulation of C and CRF17_BF strains in central Italy, characterized by NNRTI-related mutations among men engaging in high-risk behaviours. These findings underline the role of molecular epidemiology in identifying groups at increased risk of HIV-1 transmission, and in enhancing additional prevention efforts.

Comparative Evaluation of Subtyping Tools for Surveillance of Newly Emerging HIV-1 Strains

“…In this study, we aimed at assessing the necessity of updating MPhy, as well as the current performance of commonly used automated subtyping tools, in an era of changing molecular epidemiology in Western countries, including Italy (7,12,13,15,16,28). Of note, the Italian clinical context is experiencing a rapid change in circulating HIV-1 strains, mainly due to a diversified migration system, ongoing infection in the high-risk populations (mostly men having sex with men [MSM]), and specific transmission clusters (12,13).…”

“…Of note, the Italian clinical context is experiencing a rapid change in circulating HIV-1 strains, mainly due to a diversified migration system, ongoing infection in the high-risk populations (mostly men having sex with men [MSM]), and specific transmission clusters (12,13). The large number of PR/reverse transcriptase (RT) sequence data generated routinely from HIV-1-infected patients (n ϭ 13,116) and used for the present assessment offers a greater representativeness of the present findings for settings with closely related HIV epidemiological features.…”

“…However, this subtype represents only 11% of global HIV-1 infections (6). Of note, among non-B strains, subtypes A, C, and F and CRFs 01_AE and 02_AG are responsible for over 70% of all infections, and there are increasing trends of non-B subtypes and newly emerging CRFs reported in the Western world (7)(8)(9)(10)(11), including Italy (12,13).…”

“…With continuous discovery of new HIV-1 strains (https://www.hiv.lanl .gov/content/sequence/HIV/CRFs/CRFs.html) coupled with the increasing phylogeography and phylodynamics of non-B subtypes spreading into Western countries (6-8; see also WHO data at http://www.who.int/gho/hiv/en/), it would be of paramount importance to accurately identify newly emerging strains, both for efficient molecular epidemiological surveillance and for optimal clinical management of patients infected with diverse HIV-1 strains, particularly in Italy, where the migration rate is high (12,13).…”

“…(This work was presented in part as a poster at the VIIIth Italian Conference on AIDS and Antiviral Research Workshop, 6 to 8 June 2016, Milan, Italy [30]. )…”