Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies

Lourdes Anta, Josep M. Llibre, Eva Poveda, José L. Blanco, Marta Álvarez, María J. Pérez-Elías, Antonio Aguilera, Estrella Caballero, Vicente Soriano, Carmen De Mendoza, J. A. Iribarren, J. M. Gatell, E. Ribera, J. Martínez-Picado, B. Clotet, A. Jaén, D. Dalmau, J. Peraire, C. Vidal, M. RieraJ. Córdoba, J. López-Aldeguer, M. J. Galindo, C. Robledano, F. Gutiérrez, M. Álvarez, F. García, I. Viciana, J. Santos, P. Pérez-Romero, M. Leal, J. A. Pineda, F. Fernández-Cuenca, C. Rodríguez, J. Del Romero, L. Menéndez-Arias, C. Gutiérrez, S. Moreno, M. Pérez-Olmeda, J. Alcamí, A. Cañizares, J. Pedreira, C. Miralles, A. Ocampo, L. Morano, J. J. Rodríguez-Calviño, J. L. Gómez-Sirvent

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Abstract

© 2012 Wolters Kluwer Health - Lippincott Williams & Wilkins. Objective: Rilpivirine (RPV) is the latest approved nonnucleoside reverse transcriptase inhibitor (NNRTI). It displays in-vitro activity extending over other NNRTI-resistant HIV strains. There is scarce information about the rate of RPV resistance-associated mutations (RAMs) in patients failing other NNRTIs. Methods: RPV RAMs were examined in plasma samples collected from HIV patients that had recently failed NNRTI-based regimens at 22 clinics in Spain. Results: Resistance tests from a total of 1064 patients failing efavirenz (EFV) (54.5%), nevirapine (NVP) (40%) or etravirine (ETR) (5.5%) were examined. The prevalence of RPV RAMs was K101E (9.1%), K101P (1.4%), E138A (3.9%), E138G (0.3%), E138K (0.3%), E138Q (0.8%), V179L (0.2%), Y181C (21.8%), Y181I (0.5%), Y181V (0.2%), H221Y (8.3%), F227C (0.1%) and M230L (1.5%). K101E/M184I was seen in 1%. E138K/M184I were absent. Mutations L100I and V108I were significantly more frequent in patients failing EFV than NVP (7.9 vs. 0.2 and 12.2 vs. 7.3%, respectively). Conversely, Y181C, Y181I, V106A, H221Y and F227L were more prevalent following NVP than EFV failures. Using the Spanish resistance interpretation algorithm, 206 genotypes (19.3%) from patients failing NNRTI (NVP 52%, EFV 40.8% and ETR 7.8%) were considered as RPV resistant. In patients with ETR failure, cross-resistance to RPVwas seen in 27.6%,mainly as result of Y181C (81.3%), V179I (43.8%), V90I (31.3%) and V108I (18.8%). Conclusion: RPV resistance is overall recognized in nearly 20% of patients failing other NNRTIs. It is more common following ETR (27.6%) or NVP (25%) failures than EFV (14.5%). E138 mutants are rarely seen in this context.
Original languageEnglish
Pages (from-to)81-85
JournalAIDS
Volume27
Issue number1
DOIs
Publication statusPublished - 2 Jan 2013

Keywords

  • drug resistance
  • efavirenz
  • etravirine
  • nevirapine
  • rilpivirine

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