HIV-1 transmitted drug resistance in newly diagnosed individuals in Italy over the period 2015–21

Author:

Fabeni Lavinia1,Armenia Daniele2,Abbate Isabella1,Gagliardini Roberta3,Mazzotta Valentina3,Bertoli Ada4,Gennari William5,Forbici Federica1,Berno Giulia1,Piermatteo Lorenzo6,Borghi Vanni7,Pinnetti Carmela3,Vergori Alessandra3ORCID,Mondi Annalisa3,Parruti Giustino8,Di Sora Fiorella9,Iannetta Marco10,Lichtner Miriam1112,Latini Alessandra13,Mussini Cristina7,Sarmati Loredana10ORCID,Perno Carlo Federico14,Girardi Enrico15ORCID,Antinori Andrea3,Ceccherini-Silberstein Francesca16,Maggi Fabrizio1,Santoro Maria Mercedes16, ,Ceccherini-Silberstein F,Bellocchi M C,Carioti L,Santoro M M,Andreoni M,Iannetta M,Bertoli A,Sarmati L,Malagnino V,Teti E,Armenia D,Antinori A,Baldini F,Bellagamba R,Berno G,Camici M,Cicalini S,De Zottis F,Esvan R,Fabeni L,Forbici F,Fusto M,Gagliardini R,Gebremeskel S,Gili F,Girardi E,Grilli E,Grisetti S,Mastrorosa I,Mazzotta V,Mondi A,Orchi N,Ottou S,Pinnetti C,Pittalis S,Pizzi D,Plazzi M,Vergori A,Buonomini A R,Giuliani M,Latini A,Pacifici A,Perno C F,Belvisi V,Del Borgo C,Carraro A,Lichtner M,Marocco R,Borghi V,Mussini C,Gennari W

Affiliation:

1. Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS , Rome , Italy

2. Departmental Faculty, UniCamillus, Saint Camillus International University of Health Sciences , Rome , Italy

3. Clinical and Research Infectious Diseases Department, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS , Rome , Italy

4. Laboratory of Virology, Department of Laboratory Medicine, University Hospital Tor Vergata , Rome , Italy

5. Molecular Microbiology and Virology Unit, Department of Laboratory Medicine and Pathological Anatomy, Policlinic of Modena, University of Modena and Reggio Emilia , Modena , Italy

6. Department of Biology, University of Rome Tor Vergata , Rome , Italy

7. Department of Infectious Diseases, Azienda Ospedaliero-Universitaria, Policlinico of Modena , Modena , Italy

8. Infectious Diseases Unit, Pescara General Hospital , Pescara , Italy

9. Unit of Clinical Immunology, San Giovanni Addolorata Hospital , Rome , Italy

10. Department of Infectious Diseases, University Hospital Tor Vergata , Rome , Italy

11. Infectious Diseases Unit, Santa Maria Goretti Hospital, Sapienza University of Rome, Polo Pontino , Latina , Italy

12. Sant'Andrea Hospital, Clinical Infectious Diseases , Rome , Italy

13. Sexually Transmitted Infection/Human Immunodeficiency Virus Unit, San Gallicano Dermatological Institute IRCCS , Rome , Italy

14. Microbiology and Diagnostic Immunology Unit, Department of Diagnostic and Laboratory Medicine, Bambino Gesú Children's Hospital, IRCCS , Rome , Italy

15. Scientific Direction, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS , Rome , Italy

16. Department of Experimental Medicine, University of Rome Tor Vergata , Rome , Italy

Abstract

Abstract Background Transmitted drug resistance (TDR) is still a critical aspect for the management of individuals living with HIV-1. Thus, its evaluation is crucial to optimize HIV care. Methods Overall, 2386 HIV-1 protease/reverse transcriptase and 1831 integrase sequences from drug-naïve individuals diagnosed in north and central Italy between 2015 and 2021 were analysed. TDR was evaluated over time. Phylogeny was generated by maximum likelihood. Factors associated with TDR were evaluated by logistic regression. Results Individuals were mainly male (79.1%) and Italian (56.2%), with a median (IQR) age of 38 (30–48). Non-B infected individuals accounted for 44.6% (N = 1065) of the overall population and increased over time (2015–2021, from 42.1% to 51.0%, P = 0.002). TDR prevalence to any class was 8.0% (B subtype 9.5% versus non-B subtypes 6.1%, P = 0.002) and remained almost constant over time. Overall, 300 transmission clusters (TCs) involving 1155 (48.4%) individuals were identified, with a similar proportion in B and non-infected individuals (49.7% versus 46.8%, P = 0.148). A similar prevalence of TDR among individuals in TCs and those out of TCs was found (8.2% versus 7.8%, P = 0.707). By multivariable analysis, subtypes A, F, and CFR02_AG were negatively associated with TDR. No other factors, including being part of TCs, were significantly associated with TDR. Conclusions Between 2015 and 2021, TDR prevalence in Italy was 8% and remained almost stable over time. Resistant strains were found circulating regardless of being in TCs, but less likely in non-B subtypes. These results highlight the importance of a continuous surveillance of newly diagnosed individuals for evidence of TDR to inform clinical practice.

Funder

AVIRALIA Foundation

Publisher

Oxford University Press (OUP)

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