title: Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.
abstract: OBJECTIVE
  To assess the genotypic determinants of the virological response to tenofovir disoproxil fumarate (TDF) in a multicentre cohort of antiretroviral (ARV)-experienced patients receiving TDF as a part of a salvage therapy.
  
  
  METHODS
  HIV-1 genotype was assessed at baseline in a subgroup of 161 patients of the French expanded access program receiving a stable TDF-including regimen for 3 months or more. Reverse transcriptase mutations associated with the viral load decrease at month 3 with a P-value <0.15 were retained for the construction of a mutation score. The score was then validated using a multivariate analysis and bootstrap resampling method.
  
  
  RESULTS
  The strongest association with decrease in viral load was observed with a set of seven mutations (TDF mutation score) that consisted of M41L, E44D, D67N, T69D/N/S, L74V, L210W and T215Y/F RT mutations. The RT K65R mutation and the insertions at codon 69 were not included in the analysis due to low prevalences. A TDF mutation score of < or = 2 predicted the absence of resistance to TDF and > or = 6 mutations predicted resistance to TDF with corresponding reductions in viral load of -1.3 +/- 1.1, and +0.1 +/- 0.7 log10 copies/ml, respectively. In patients with a TDF mutation score of 3-5, the decrease in viral load was -0.8 +/- 1.0 log10 copies/ml and was considered possibly resistant. In the multivariate analysis, a TDF mutation score > or = 6, previous use of amprenavir, indinavir and lopinavir, and co-prescription of didanosine were associated with a worse virological response. The bootstrap analysis showed the robustness of the TDF mutation score.
  
  
  CONCLUSIONS
  In ARV-experienced patients receiving TDF-containing regimens, a score derived from seven reverse transcriptase mutations was shown to be independently predictive of the virological response.
authors.affiliation: Laboratoire de Virologie, CHU de Bordeaux, France. bernard.masquelier@chu-bordeaux.fr
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Catherine
authors.initials: C
authors.lastname: Tamalet
authors.forename: Brigitte
authors.initials: B
authors.lastname: Montès
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Laurence
authors.initials: L
authors.lastname: Bocket
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.forename: Véronique
authors.initials: V
authors.lastname: Schneider
authors.forename: Virginie
authors.initials: V
authors.lastname: Ferré
authors.forename: Annick
authors.initials: A
authors.lastname: Ruffault
authors.forename: Pierre
authors.initials: P
authors.lastname: Palmer
authors.forename: Aldo
authors.initials: A
authors.lastname: Trylesinski
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vézinet
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D003062:Codon; D015331:Cohort Studies; D005602:France; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D015999:Multivariate Analysis; D063065:Organophosphonates / Q000097:blood / Q000627:therapeutic use*; D017354:Point Mutation / Q000187:drug effects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir
chemical_list: D003062:Codon; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine