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Non-B subtypes account for a large proportion of clustered primary HIV-1 infections in Italy
  1. Giorgio Bozzi1,
  2. Lavinia Fabeni2,
  3. Isabella Abbate2,
  4. Giulia Berno2,
  5. Antonio Muscatello1,
  6. Lucia Taramasso1,3,
  7. Massimiliano Fabbiani4,
  8. Silvia Nozza5,
  9. Giuseppe Tambussi5,
  10. Stefano Rusconi6,7,
  11. Andrea Giacomelli6,
  12. Emanuele Focà8,
  13. Carmela Pinnetti2,
  14. Gabriella d'Ettorre9,
  15. Cristina Mussini10,
  16. Vanni Borghi10,
  17. Benedetto Maurizio Celesia11,
  18. Giordano Madeddu12,
  19. Antonio Di Biagio13,
  20. Diego Ripamonti14,
  21. Nicola Squillace15,
  22. Andrea Antinori2,
  23. Andrea Gori1,16,
  24. Maria Rosaria Capobianchi2,
  25. Alessandra Bandera1,16
  26. the INACTION study group
    1. 1Infectious Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico – Milan, Milan, Lombardia, Italy
    2. 2Virology and Biosafety Laboratories Unit and HIV/AIDS Clinical Unit, National Institute for Infectious Diseases, “Lazzaro Spallanzani”- IRCCS Rome, Rome, Italy
    3. 3Infection Diseases Unit, IRCCS Policlinico San Martino Hospital, Genoa, Italy
    4. 4Infectious and Tropical Diseases Unit, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
    5. 5Clinic of Infectious Diseases, San Raffaele Hospital, University Vita Salute, Milan, Italy
    6. 6Infectious Diseases Unit, Department of Biomedical and Clinical Sciences “Luigi Sacco” Hospital, University of Milan, Milan, Italy
    7. 7Infectious Diseases Unit, Ospedale Civile di Legnano, ASST Ovest Milanese, Legnano, Italy
    8. 8Division of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili Hospital, Brescia, Italy
    9. 9Infectious Diseases Unit, Umberto I Hospital, La Sapienza University, Rome, Rome, Italy
    10. 10Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena Hospital, Modena, Italy
    11. 11Unit of Infectious Diseases, Garibaldi Hospital, Catania, Italy
    12. 12Department of Medical, Surgical and Experimental Sciences, Unit of Infectious Diseases, University of Sassari, Sassari, Italy
    13. 13Department of Health Sciences (DiSSal), University of Genoa, Italy, Genoa, Italy
    14. 14Division of Infectious Diseases, ASST Papa Giovanni XXIII, Bergamo, Italy
    15. 15Infectious Diseases Unit, Department of Internal Medicine, ASST San Gerardo, Monza, Italy
    16. 16Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
    1. Correspondence to Dr Giorgio Bozzi, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico - Milan, Infection Diseases Unit, IRCCS Foundation Maggiore Policlinico Hospital, Via Francesco Sforza, 35, 20122, Milan, Lombardia, Italy; giorgio.bozzi{at}policlinico.mi.it

    Abstract

    Objectives and design Using pol sequences obtained for routine resistance testing, we characterised the molecular patterns of HIV-1 transmission and factors associated with being part of a transmission cluster among individuals who in 2008–2014 presented with primary HIV-1 infection (PHI) at 11 urban centres across Italy.

    Methods Pol sequences were obtained by Sanger sequencing. Transmission clusters were identified by phylogenetic analysis (maximum likelihood method, confirmed by Bayesian analysis). Multivariable logistic regression explored factors associated with a participant being part of a transmission cluster.

    Results The PHI cohort comprised 186 participants (159/186, 85.5% males) with median age 44 years, median CD4 count 464 cells/mm3 and median plasma HIV-1 RNA 5.6 log10 copies/mL. Drug resistance associated mutations were found in 16/186 (8.6%). A diversity of non-B subtypes accounted for 60/186 (32.3%) of all infections. A total of 17 transmission clusters were identified, including 44/186 (23.7%) participants. Each cluster comprised 2–6 sequences. Non-B subtypes accounted for seven clusters and 22/44 (50%) of clustered sequences. In multivariable logistic regression analysis, factors associated with being part of a transmission cluster comprised harbouring a non-B subtype (adjusted OR (adjOR) 2.28; 95% CI 1.03 to 5.05; p=0.04) and showing a lower plasma HIV-1 RNA (adjOR 0.80, 95% CI 0.64 to 0.99; p=0.04).

    Conclusions There was a large contribution of diverse non-B subtypes to transmission clusters among people presenting with acute or recent HIV-1 infection in this cohort, illustrating the evolving dynamics of the HIV-1 epidemic in Italy, where subtype B previously dominated.

    • HIV
    • MOLECULAR EPIDEMIOLOGY
    • Disease Transmission, Infectious

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    Footnotes

    • Handling editor Apostolos Beloukas

    • MRC and AB contributed equally.

    • GB and LF contributed equally.

    • Collaborators The INACTION study group participating physicians and centres are as follows: Andrea Gori, Antonio Muscatello, Alessandra Bandera (Ospedale Maggiore Policlinico Milano); Nicola Squillace (Monza); Giuseppe Tambussi, Silvia Nozza, Marco Ripa, Raffele Dell’Acqua, Elena Bruzzesi, Andrea Mastrangelo (H San Raffaele, Milano); Andrea Antinori, Carmela Pinnetti (INMI Spallanzani Roma); Andrea Calcagno, Gianfranco Orofino, Ilaria De Benedetto, Micol Ferrara (Torino); Cristina Mussini, Vanni Borghi, Federica Carli (Modena); Benedetto Maurizio Celesia (Catania); Lucio Cosco, Carlo Torti (Catanzaro); Gabriella D’Ettorre (Umberto I, Roma); Antonio Di Biagio, Lucia Taramasso (Genova); Emanuele Focà, Eugenia Quiros-Roland (Brescia); Antonina Franco (Siracusa); Diego Ripamonti, Franco Maggiolo (Bergamo); Roberto Gulminetti, Massimiliano Fabbiani (Pavia); Sandro Piga, Marzia Garau, Marco Campus (Cagliari); Stefano Rusconi, Tiziana Formenti, Arianna Gabrieli, Alessia Lai, Cecilia Bonazzetti, Andrea Giacomelli (H Sacco, Milano); Giulia Marchetti, Camilla Tincati (H San Paolo, Milano); Antonella Cingolani (H Gemelli, Roma); Giordano Madeddu (Sassari).

    • Contributors GB ad LF together with AG, MRC and AB conceived and drafted the present work, and they acted as liaisons for the study group. LF, IA and GB, under the supervision of AA and MRC, conducted the analyses. AM, LT, MF, SN, GT, SR, AG, EF, CP, GE, CM, VB, BMC, GM, ADB, DR, NS and AA were involved in clinical care, data collection and contributed to the writing of the manuscript. All authors revised the manuscript critically and approved the final version of the manuscript. All the authors listed have substantially contributed to the study's conception, design and/or performance.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests LT reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare and no other conflict of interest. MF reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare, BMS, MSD and no other conflict of interest. SR reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare and no other conflict of interest. AG reports past (within 36 months) financial relationships (educational support) with Mylan and no other conflict of interest. EF reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare, MSD and no other conflict of interest. CP reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Janssen. GM reports past (within 36 months) financial relationships (advisory board membership or consultancy fees, speakers’ honoraria or travel support) with Gilead Sciences, Janssen, Viiv Healthcare, MSD and no other conflict of interest. AG reports past (within 36 months) grant/research supports, honoraria or consultation fees, speaker’s bureau compensation and/or travel support from Abbvie, Astellas, BMS, Boeringher, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, ViiV and no other conflict of interest.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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