Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes

Lourdes Anta, José L. Blanco, Josep M. Llibre, Federico García, María J. Pérez-Elías, Aatonio Aguilera, Pilar Pérez-Romero, Estrella Caballero, Carmen Vidal, Angelina Cañizares, Félix Gutiérrez, David Dalmau, José A. Iribarren, Vicente Soriano, Carmen De Mendozal

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9 Citations (Scopus)

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%, P1/40.13, and 10.5% versus 7.4%, P1/40.23, 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%, P1/40.004), 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%, P1/40.998). 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. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Original languageEnglish
Article numberdkt146
Pages (from-to)1994-2002
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number9
DOIs
Publication statusPublished - 1 Sep 2013

Keywords

  • Darunavir
  • Drug resistance
  • Etravirine
  • HIV-1 diversity
  • Rilpivirine
  • Tipranavir

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