The algorithm used for the interpretation of doravirine transmitted drug resistance strongly influences clinical practice and guideline recommendations. (6th February 2020)

• Record Type: Journal Article
• Authors: 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; Gómez-Sirvent, Juan Luis; Peraire, Joaquim; Portilla, Joaquín; Caballero, Estrella; Alejos, Belén; García, Federico; Moreno, Santiago
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 5(2020)
• Page Start: 1294
• Page End: 1300
• Publication Date: 2020-02-06
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa009
• Languages: English
• ISSNs: 0305-7453

Abstract

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.