title: Early virological failure with a combination of tenofovir, didanosine and efavirenz.
abstract: OBJECTIVE
  To describe the occurrence of a high early virological failure (VF) rate and development of resistance mutations in antiretroviral-naive patients receiving tenofovir, didanosine and efavirenz.
  
  
  METHODS
  HIV-infected antiretroviral-naive patients with viral load > or =30 000 copies/ml were enrolled in a pilot randomized trial of tenofovir/didanosine (250 mg)/ efavirenz with (arm A) or without (arm B) lopinavir/r for the first 12 weeks. As six cases of early VF (a drop of <2 log at month 3, or a rebound of >1 log from the nadir) were detected (five in arm B and one in arm A who had previously stopped lopinavir/r) an unplanned interim analysis was performed.
  
  
  RESULTS
  A total of 29 out of 36 enrolled patients completed at least 3 months of follow-up and were included in the interim analysis. An intent-to-treat analysis showed treatment failure in 7/15 (46.7%) patients in arm B (five VF, one lost, one switched) versus 2/14 (14.3%) in arm A (one lost, one switched) (P=0.109). The patient in arm A who interrupted lopinavir/r at day 3 and continued with tenofovir/didanosine/efavirenz later developed VF. At baseline, 6/6 VF patients had VL >100000 copies/ml and an advanced stage of disease (CD4 <200 plus CDC stage C or B3) versus 0/8 non-VF patients taking the triple drug regimen (P<0.001). At failure, G190S/E alone or associated with K103N and K101R mutations was detected in five patients, and K103N/L1001/V108l in the sixth patient. Additionally, L74V/I and K65R were detected in four and two patients, respectively.
  
  
  CONCLUSIONS
  A high early virological failure rate and the occurrence of resistance mutations were detected in a group of antiretroviral-naive patients treated with tenofovir/didanosine/efavirenz.
authors.affiliation: Infectious Disease Service, Hospital Universitari de Bellvitge, Barcelona, Spain. dpodzamczer@csub.scs.es
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Gatell
authors.forename: Jordi
authors.initials: J
authors.lastname: Niubo
authors.forename: David
authors.initials: D
authors.lastname: Dalmau
authors.forename: Agathe
authors.initials: A
authors.lastname: Leon
authors.forename: Hernando
authors.initials: H
authors.lastname: Knobel
authors.forename: Carolina
authors.initials: C
authors.lastname: Polo
authors.forename: Daniel
authors.initials: D
authors.lastname: Iniguez
authors.forename: Isaac
authors.initials: I
authors.lastname: Ruiz
mesh_terms: D000225:Adenine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D003521:Cyclopropanes; D016049:Didanosine / Q000008:administration & dosage*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage*; D010078:Oxazines / Q000008:administration & dosage*; D011744:Pyrimidinones / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir; D013997:Time Factors; D017211:Treatment Failure; D014766:Viremia / Q000188:drug therapy / Q000821:virology
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D010078:Oxazines; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz; D016049:Didanosine