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Open Access Highly Accessed Research article

Trends and correlates of HIV-1 resistance among subjects failing an antiretroviral treatment over the 2003–2012 decade in Italy

Marco Franzetti1*, Michela Violin1, Andrea Antinori2, Andrea De Luca3, Francesca Ceccherini-Silberstein4, Nicola Gianotti5, Carlo Torti67, Stefano Bonora8, Maurizio Zazzi9 and Claudia Balotta1

Author Affiliations

1 Department of Biomedical and Clinical Sciences 'L. Sacco', Infectious Diseases and Immunopathology Section, University of Milan, Milan, Italy

2 National Institute for Infectious Diseases ‘L. Spallanzani’ IRCCS, Roma, Italy

3 Infectious Diseases Unit, Siena University Hospital, Siena, Italy

4 Department of Experimental Medicine, University of Rome Tor Vergata, Roma, Italy

5 Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy

6 University Department of Infectious Diseases, University of Brescia, Brescia, Italy

7 Unit of Infectious Diseases, Department of Medical and Surgical Sciences, University “Magna Graecia”, Catanzaro, Italy

8 University of Turin, Turin, Italy

9 Department of Molecular Biology, University of Siena, Siena, Italy

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BMC Infectious Diseases 2014, 14:398  doi:10.1186/1471-2334-14-398

Published: 18 July 2014

Abstract

Background

Despite a substantial reduction in virological failures following introduction of new potent antiretroviral therapies in the latest years, drug resistance remains a limitation for the control of HIV-1 infection. We evaluated trends and correlates of resistance in treatment failing patients in a comprehensive database over a time period of relevant changes in prescription attitudes and treatment guidelines.

Methods

We analyzed 6,796 HIV-1 pol sequences from 49 centres stored in the Italian ARCA database during the 2003–2012 period. Patients (n = 5,246) with viremia > 200 copies/mL received a genotypic test while on treatment. Mutations were identified from IAS-USA 2013 tables. Class resistance was evaluated according to antiretroviral regimens in use at failure. Time trends and correlates of resistance were analyzed by Cochran-Armitage test and logistic regression models.

Results

The use of NRTI backbone regimens slightly decreased from 99.7% in 2003–2004 to 97.4% in 2010–2012. NNRTI-based combinations dropped from 46.7% to 24.1%. PI-containing regimens rose from 56.6% to 81.7%, with an increase of boosted PI from 36.5% to 68.9% overtime. In the same reference periods, Resistance to NRTIs, NNRTIs and PIs declined from 79.1% to 40.8%, from 77.8% to 53.8% and from 59.8% to 18.9%, respectively (p < .0001 for all comparisons). Dual NRTI + NNRTI and NRTI + PI resistance decreased from 56.4% to 33.3% and from 36.1% to 10.5%, respectively. Reduced risk of resistance over time periods was confirmed by a multivariate analysis.

Conclusions

Mutations associated with NRTIs, NNRTIs and PIs at treatment failure declined overtime regardless of specific class combinations and epidemiological characteristics of treated population. This is likely due to the improvement of HIV treatment, including both last generation drug combinations and prescription guidelines.

Keywords:
HIV; Antiretroviral therapy; HIV acquired resistance