학술논문
Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes
Document Type
Academic Journal
Author
Anta, Lourdes; Blanco, José L.; Llibre, Josep M.; García, Federico; Pérez-Elías, María J.; Aguilera, Antonio; Pérez-Romero, Pilar; Caballero, Estrella; Vidal, Carmen; Cañizares, Angelina; Gutiérrez, Félix; Dalmau, David; Iribarren, José A.; Soriano, Vicente; de Mendoza, Carmen; Iribarren, JA; Blanco, JL; Gatell, JM; Caballero, E; Ribera, E; Llibre, JM; Martínez-Picado, J; Clotet, B; Jaén, A; Dalmau, D; Peraire, J; Vidal, F; Vidal, C; Riera, M; Córdoba, J; López-Aldeguer, J; Galindo, MJ; Robledano, C; Gutiérrez, F; Álvarez, M; Chueca, N; García, F; Viciana, I; Santos, J; Pérez-Romero, P; Leal, M; Parra, M; Palomares, JC; Pineda, JA; Fernández-Cuenca, F; Rodríguez, C; del Romero, J; Menéndez-Arias, L; Pérez-Elías, MJ; Gutiérrez, C; Moreno, S; Pérez-Olmeda, M; Alcamí, J; Cañizares, A; Pedreira, J; Miralles, C; Ocampo, A; Morano, L; Rodríguez-Calviño, JJ; Aguilera, A; Gómez-Sirvent, JL; Anta, L; Poveda, E; Soriano, V; de Mendoza, C
Source
Journal of Antimicrobial Chemotherapy. Sep 01, 2013 68(9):1994-2002
Subject
Language
English
ISSN
0305-7453
Abstract
OBJECTIVES: Limited data are available on resistance to etravirine, rilpivirine, darunavir and tipranavir in patients infected with HIV-1 non-B subtypes, in which natural polymorphisms at certain positions could influence the barrier and/or pathways to drug resistance. METHODS: FASTA format sequences from the reverse transcriptase and protease genes recorded within the Spanish Drug Resistance database (ResRIS) were examined. RESULTS: From 8272 genotypes derived from 5930 different HIV-1 patients included in ResRIS, 5276 genotypes had complete treatment information. Overall, 85% were from antiretroviral-experienced subjects and 7.5% belonged to HIV-1 non-B subtypes: CRF02_AG, C, F and G being the most prevalent variants. For etravirine, only G190A was more prevalent in B than non-B subtypes, whereas V90I and V179E were more frequent in non-B than B subtypes. For rilpivirine, V108I and Y188I were more frequent in B than non-B subtypes, whereas V90I was more prevalent in non-B subtypes. Despite these differences, the overall prevalence of resistance did not differ significantly when comparing etravirine or rilpivirine in B versus non-B subtypes (11.3% versus 7.4%, P = 0.13, and 10.5% versus 7.4%, P = 0.23, respectively). Despite more frequent natural polymorphisms in non-B than B subtypes at tipranavir resistance positions, the prevalence of tipranavir resistance was greater in B than non-B subtypes (11% versus 4.3%, P = 0.004), reflecting a greater antiretroviral exposure in the former. Darunavir resistance did not differ significantly when comparing B and non-B subtypes (5.8% versus 5.5%, P = 0.998). CONCLUSIONS: The rate of resistance to the most recently approved protease and non-nucleoside reverse transcriptase inhibitors is low in antiretroviral-experienced patients, regardless of the HIV-1 subtype.