Carlos Guerrero-Beltrán1, Javier Martínez-Sanz2, Marta Álvarez1, Julián Olalla3, Mónica García-Álvarez4, Jose Antonio Iribarren5, Mar Masiá6, Marta Montero7, Silvia García-Bujalance8, José Ramón Blanco9, María Rivero10, Lucio Jesús García-Fraile11, Núria Espinosa12, Carmen Rodríguez13, Antonio Aguilera14, María Carmen Vidal-Ampurdanes15, Marina Martínez16, Asunción Iborra17, Arkaitz Imaz18, Juan Luis Gómez-Sirvent19, Joaquim Peraire20, Joaquín Portilla21, Estrella Caballero22, Belén Alejos23, Federico García1, Santiago Moreno2. 1. Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Granada, Spain. 2. Hospital Ramón y Cajal, Madrid, Spain. 3. Hospital Costa del Sol, Marbella (Málaga), Spain. 4. Hospital Doce de Octubre, Madrid, Spain. 5. Hospital Universitario Donostia, San Sebastian, Spain. 6. Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Spain. 7. Hospital Universitario La Fe, Valencia, Spain. 8. Hospital Universitario La Paz/IdiPAZ, Madrid, Spain. 9. Hospital San Pedro, Logroño, Spain. 10. Hospital de Navarra, Pamplona, Spain. 11. Hospital La Princesa, Madrid, Spain. 12. Hospital Virgen del Rocío, Sevilla, Spain. 13. Centro Sanitario Sandoval, Madrid, Spain. 14. Complexo Hospitalario Santiago Compostela, Universidad de Santiago de Compostela, Santiago de Compostela, Spain. 15. Hospital Son Espases, Mallorca, Spain. 16. Hospital Universitari Mutua Terrassa, Terrasa, Spain. 17. Hospital Virgen Arrixaca, Murcia, Spain. 18. Hospital Universitario de Bellvitge, Barcelona, Spain. 19. Hospital Universitario de Canarias, Las Palmas de Gran Canaria, Spain. 20. Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain. 21. Hospital Alicante, Alicante, Spain. 22. Hospital Vall D'Hebron, Barcelona, Spain. 23. Instituto de Salud Carlos III, Madrid, Spain.
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.
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-infectedpatients, 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.
Authors: Kim Steegen; Michelle Moorhouse; Annemarie Mj Wensing; Willem Df Venter; Lucia Hans Journal: J Int AIDS Soc Date: 2021-05 Impact factor: 5.396
Authors: Ernest Asante-Appiah; Johnny Lai; Hong Wan; Dongmei Yang; Elizabeth Anne Martin; Peter Sklar; Daria Hazuda; Christos J Petropoulos; Charles Walworth; Jay A Grobler Journal: Antimicrob Agents Chemother Date: 2021-09-27 Impact factor: 5.191