title: Resistance profiles of emtricitabine and lamivudine in tenofovir-containing regimens.
abstract: OBJECTIVE
  To compare the frequency of the selection of the M184V/I resistance mutation in HIV-infected patients who experienced virological failure while receiving emtricitabine (FTC) or lamivudine (3TC), administered with tenofovir disoproxil fumarate (TDF) and either efavirenz (EFV) or a ritonavir-boosted protease inhibitor (PI; lopinavir or atazanavir).
  
  
  METHODS
  Patient data held at two clinical centres in France were analysed retrospectively. Eligible patients had experienced virological suppression (plasma HIV RNA <200 copies/mL) for ≥ 6 months before experiencing their first virological failure (at least two measurements of plasma HIV RNA ≥ 200 copies/mL).
  
  
  RESULTS
  Of the 880 patients eligible for the study, 278 patients had experienced virological failure while receiving FTC + TDF + ritonavir-boosted PI, 257 while receiving FTC + TDF + EFV, 178 while receiving 3TC + TDF + EFV and 167 while receiving 3TC + TDF + ritonavir-boosted PI. Proportions of patients harbouring the M184V/I mutation were 24% (n = 62) for those who received FTC + TDF + EFV versus 51% (n = 91) for 3TC + TDF + EFV (P < 0.0001; Fisher's exact test); proportions were 11% (n = 30) for FTC + TDF + ritonavir-boosted PI versus 22% (n = 37) for 3TC + TDF + ritonavir-boosted PI (P = 0.002; Fisher's exact test). The use of lamivudine versus emtricitabine (P = 0.001), non-nucleoside reverse transcriptase inhibitors versus ritonavir-boosted PIs (P = 0.01) and the level of viral load at the time of virological failure (P = 0.01) were associated with selection of the M184V/I mutation (logistic regression analysis).
  
  
  CONCLUSIONS
  Emtricitabine and lamivudine showed differing resistance profiles when administered in combination with tenofovir disproxil fumarate and either efavirenz or a ritonavir-boosted PI. The prevalence of the M184V/I resistance mutation was significantly lower in patients who received emtricitabine and tenofovir disoproxil fumarate than in those who received lamivudine and tenofovir disoproxil fumarate.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMR S-943, Paris F-75013, France. anne-genevieve.marcelin@psl.aphp.fr
authors.forename: A G
authors.initials: AG
authors.lastname: Marcelin
authors.forename: C
authors.initials: C
authors.lastname: Charpentier
authors.forename: M
authors.initials: M
authors.lastname: Wirden
authors.forename: R
authors.initials: R
authors.lastname: Landman
authors.forename: M A
authors.initials: MA
authors.lastname: Valantin
authors.forename: A
authors.initials: A
authors.lastname: Simon
authors.forename: C
authors.initials: C
authors.lastname: Katlama
authors.forename: P
authors.initials: P
authors.lastname: Yeni
authors.forename: D
authors.initials: D
authors.lastname: Descamps
authors.forename: C
authors.initials: C
authors.lastname: Aubron-Olivier
authors.forename: V
authors.initials: V
authors.lastname: Calvez
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005260:Female; D005602:France; D006678:HIV / Q000187:drug effects* / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D063065:Organophosphonates / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D012641:Selection, Genetic; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D019259:Lamivudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine