1. The algorithm used for the interpretation of doravirine transmitted drug resistance strongly influences clinical practice and guideline recommendations.
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Guerrero-Beltrán, Carlos, Martínez-Sanz, Javier, Álvarez, Marta, Olalla, Julián, García-Álvarez, Mónica, Iribarren, Jose Antonio, Masiá, Mar, Montero, Marta, García-Bujalance, Silvia, Blanco, José Ramón, Rivero, María, García-Fraile, Lucio Jesús, Espinosa, Núria, Rodríguez, Carmen, Aguilera, Antonio, Vidal-Ampurdanes, María Carmen, Martínez, Marina, Iborra, Asunción, Imaz, Arkaitz, and Gómez-Sirvent, Juan Luis
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HIV infection epidemiology , *ANTI-HIV agents , *HIV infections , *PYRIDINE , *RESEARCH , *GENETIC mutation , *HETEROCYCLIC compounds , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *COMPARATIVE studies , *GENOTYPES , *DISEASE prevalence , *DRUG resistance in microorganisms , *ALGORITHMS , *PHARMACODYNAMICS - Abstract
Objectives: We report the results of the reverse transcriptase (RT)/protease (PR) transmitted drug resistance (TDR) prevalence study in 2018, focusing on doravirine resistance-associated mutations and the differences observed when Stanford or French National Agency for AIDS Research (ANRS)/Spanish Network of AIDS Research (RIS)/IAS-USA resistance interpretation algorithms are used to describe clinically relevant resistance.Methods: We used the WHO 2009 list to investigate the prevalence of NNRTI, NRTI and PI TDR, in treatment-naive HIV-1-infected patients, adding mutations E138A/G/K/Q/R, V106I, V108I, V179L, G190Q, H221Y, F227C/L/V, M230IDR, L234I, P236L and Y318F in RT. The prevalence of doravirine resistance-associated mutations, as described by Soulie et al. in 2019, was evaluated. Clinically relevant TDR was investigated using the latest versions of ANRS, RIS, IAS-USA and Stanford algorithms.Results: NNRTI mutations were detected in 82 of 606 (13.5%) patients. We found 18 patients (3.0%) with NRTI mutations and 5 patients (0.8%) with PI mutations. We detected 11 patients harbouring doravirine resistance-associated mutations (prevalence of 1.8%). Furthermore, we observed important differences in clinically relevant resistance to doravirine when ANRS/RIS (0.7%), IAS-USA (0.5%) or Stanford algorithms (5.0%) were used. V106I, which was detected in 3.8% of the patients, was the main mutation driving these differences. V106I detection was not associated with any of the clinical, demographic or virological characteristics of the patients.Conclusions: The prevalence of NRTI and PI TDR remains constant in Spain. Doravirine TDR is very infrequent by RIS/ANRS/IAS-USA algorithms, in contrast with results using the Stanford algorithm. Further genotype-phenotype studies are necessary to elucidate the role of V106I in doravirine resistance. [ABSTRACT FROM AUTHOR]- Published
- 2020
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