title: Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study.
abstract: BACKGROUND
  To assess the efficacy and safety of the triple NRTI combination of abacavir (ABC), lamivudine (3TC), and tenofovir (TDF) in a once-daily regimen.
  
  
  METHODS
  38 HIV-naive patients (pts) were treated in a prospective open-arm study over 48 weeks (W48). Virological failure was defined as never achieving plasma HIV-1 RNA < 400 copies/mL or rebound of > or = 0.7 log10.
  
  
  RESULTS
  12/36 (33%) pts had virologic failure at W24 and 10 additional pts had HIV RNA > 50 copies/mL at W12 or W24. There was a significant association between baseline viral load (VL) and virologic failure in 0%, 29%, and 64% pts with baseline VL levels < 4, 4-5, and > 5 log10 copies/mL, respectively (p = .014). 76% of pts developed K65R and M184V/I mutations by W24, and 19% developed M184V/I alone. At W4, 86% of pts had adequate plasma Cmin for the 3 drugs. 14 pts with K65R and M184V/I were given a rescue therapy with a successful outcome (< 50 copies/mL; median follow-up 48 weeks).
  
  
  CONCLUSIONS
  Convergent genetic pathway to resistance, in conjunction with lower antiretroviral potency, may explain the high rate of selection K65R and M184V mutations. These mutations did not appear to have a negative effect on rescue therapy with a variety of regimens.
authors.affiliation: Bichat Claude Bernard Hospital, Paris, France. landman@bichat.inserm.fr
authors.forename: R
authors.initials: R
authors.lastname: Landman
authors.forename: D
authors.initials: D
authors.lastname: Descamps
authors.forename: G
authors.initials: G
authors.lastname: Peytavin
authors.forename: A
authors.initials: A
authors.lastname: Trylesinski
authors.forename: C
authors.initials: C
authors.lastname: Katlama
authors.forename: P M
authors.initials: PM
authors.lastname: Girard
authors.forename: B
authors.initials: B
authors.lastname: Bonnet
authors.forename: P
authors.initials: P
authors.lastname: Yeni
authors.forename: M
authors.initials: M
authors.lastname: Bentata
authors.forename: C
authors.initials: C
authors.lastname: Michelet
authors.forename: A
authors.initials: A
authors.lastname: Benalycherif
authors.forename: F
authors.initials: F
authors.lastname: Brun Vezinet
authors.forename: M D
authors.initials: MD
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Flandre
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010865:Pilot Projects; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000097:blood; D000099227:Abacavir
chemical_list: D015224:Dideoxynucleosides; D019259:Lamivudine; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir