title: Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our finding of a stable time trend of K65R despite elevated use of tenofovir illustrates increased potency of current HIV-1 therapy including tenofovir.
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium. kristof.theys@rega.kuleuven.ac.be
authors.forename: K
authors.initials: K
authors.lastname: Theys
authors.forename: J
authors.initials: J
authors.lastname: Snoeck
authors.forename: J
authors.initials: J
authors.lastname: Vercauteren
authors.forename: A B
authors.initials: AB
authors.lastname: Abecasis
authors.forename: A-M
authors.initials: AM
authors.lastname: Vandamme
authors.forename: R J
authors.initials: RJ
authors.lastname: Camacho
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D020125:Mutation, Missense; D063065:Organophosphonates / Q000008:administration & dosage*; D012641:Selection, Genetic; D000068698:Tenofovir; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000225:Adenine