Objectives: The aim of this study was to evaluate acquired drug resistance in Italy in the 2009-2018 period.Methods: We analysed 3094 patients from the Italian ARCA database who had failed antiretroviral treatment and who had received a genotypic test after 6 months of treatment. Drug resistance mutations were identified using International AIDS Society (IAS)-USA tables and the Stanford HIVdb algorithm. The global burden of acquired resistance was calculated among all subjects with antiretroviral failure. Time trends and correlates of resistance were analysed using standard statistical tests.Results: Patients of non-European origin and non-B subtypes increased significantly from 11.5% (103/ 896) to 19.2% (33/172) and from 13.1% (141/1079) to 23.8% (53/223), respectively, over time. Overall, 14.5% (448/3094), 12.1% (374/3094) and 37.8% (1169/3094) of patients failed first, second and later lines, respectively. According to both IAS and HIVdb, in the study period resistance to any class, nucleoside reverse inhibitor, non-nucleoside reverse inhibitor, and protease inhibitors (PIs) declined significantly. Integrase strand transfer inhibitor (INSTI) resistance declined significantly from 31% (36/116) to 20.8% (41/197) according to HIVdb but not to IAS. Divergent data were highlighted regarding the proportion of non-European patients carrying any, PI and INSTI resistance using IAS tables compared with the Stanford HIVdb algorithm, as the former failed to detect a decrease in resistance while the latter indicates a reduction of 1.6-, 5- and 1.8-fold resistance for such drug classes. In the multivariate analysis, the risk of resistance increased in patients with a larger number of treatment lines and higher viraemia and decreased in those starting therapy in the last biennium of the study.Discussion: A marked reduction in drug resistance was observed over 10 years, compatible with higher genetic barrier and potency of new antiretrovirals. Nonetheless, concerns remain for subjects with non-B subtypes when using mutation lists instead of interpretation systems because of the extensive polymorphism of the protease region. (C) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Marked decrease in acquired resistance to antiretrovirals in latest years in Italy

Lo Caputo, Sergio;
2021-01-01

Abstract

Objectives: The aim of this study was to evaluate acquired drug resistance in Italy in the 2009-2018 period.Methods: We analysed 3094 patients from the Italian ARCA database who had failed antiretroviral treatment and who had received a genotypic test after 6 months of treatment. Drug resistance mutations were identified using International AIDS Society (IAS)-USA tables and the Stanford HIVdb algorithm. The global burden of acquired resistance was calculated among all subjects with antiretroviral failure. Time trends and correlates of resistance were analysed using standard statistical tests.Results: Patients of non-European origin and non-B subtypes increased significantly from 11.5% (103/ 896) to 19.2% (33/172) and from 13.1% (141/1079) to 23.8% (53/223), respectively, over time. Overall, 14.5% (448/3094), 12.1% (374/3094) and 37.8% (1169/3094) of patients failed first, second and later lines, respectively. According to both IAS and HIVdb, in the study period resistance to any class, nucleoside reverse inhibitor, non-nucleoside reverse inhibitor, and protease inhibitors (PIs) declined significantly. Integrase strand transfer inhibitor (INSTI) resistance declined significantly from 31% (36/116) to 20.8% (41/197) according to HIVdb but not to IAS. Divergent data were highlighted regarding the proportion of non-European patients carrying any, PI and INSTI resistance using IAS tables compared with the Stanford HIVdb algorithm, as the former failed to detect a decrease in resistance while the latter indicates a reduction of 1.6-, 5- and 1.8-fold resistance for such drug classes. In the multivariate analysis, the risk of resistance increased in patients with a larger number of treatment lines and higher viraemia and decreased in those starting therapy in the last biennium of the study.Discussion: A marked reduction in drug resistance was observed over 10 years, compatible with higher genetic barrier and potency of new antiretrovirals. Nonetheless, concerns remain for subjects with non-B subtypes when using mutation lists instead of interpretation systems because of the extensive polymorphism of the protease region. (C) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11369/431195
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