Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir

K. Theys, J. Snoeck, J. Vercauteren, A. B. Abecasis, A. M. Vandamme, R. J. Camacho, Kamal Mansinho, Ana Cláudia Miranda, Isabel Aldir, Fernando Ventura, Jaime Nina, Fernando Borges, Emília Valadas, Manuela Doroana, Francisco Antunes, Maria João Aleixo, Maria João Águas, Júlio Botas, Teresa Branco, José VeraInês Vaz Pinto, Joana Sá, Luis Duque, António Diniz, Ana Mineiro, Flora Gomes, Carlos Santos, Domitília Faria, Paula Fonseca, Paula Proença, Luís Tavares, Cristina Guerreiro, Jorge Narciso, Telo Faria, Eugénio Teófilo, Sofia Pinheiro, Isabel Germano, Umbelina Caixas, Nancy Faria, Ana Paula Reis, Margarida Bentes Jesus, Graça Amaro, Fausto Roxo, Ricardo Abreu, Isabel Neves

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Objectives: The use of tenofovir is highly associated with the emergence of mutation K65R, which confers broad resistance to nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs), especially when tenofovir is combined with other NRTIs also selecting for K65R. Although recent HIV-1 treatment guidelines discouraging these combinations resulted in reduced K65R selection with tenofovir, updated information on the impact of currently recommended regimens on the population selection rate of K65R is presently lacking. Methods: In this study, we evaluated changes over time in the selection rate of resistance mutation K65R in a large population of 2736 HIV-1-infected patients failing combination antiretroviral treatment between 2002 and 2010. Results: The K65R resistance mutation was detected in 144 patients, a prevalence of 5.3%. A large majority of observed K65R cases were explained by the use of tenofovir, reflecting its wide use in clinical practice. However, changing patterns over time in NRTIs accompanying tenofovir resulted in a persistent decreasing probability of K65R selection by tenofovir-based therapy. The currently recommended NRTI combination tenofovir/emtricitabine was associated with a low probability of K65R emergence. For any given dual NRTI combination including tenofovir, higher selection rates of K65R were consistently observed with a non-nucleoside reverse transcriptase inhibitor than with a protease inhibitor as the third agent. Discussion: Our finding of a stable time trend of K65R despite elevated use of tenofovir illustrates increased potency of current HIV-1 therapy including tenofovir.

Original languageEnglish
Article numberdks380
Pages (from-to)419-423
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Epidemiology
  • Guidelines
  • Treatment
  • Trend
  • Virology

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