title: Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy.
abstract: OBJECTIVE
  To investigate the impact of 215 HIV-1 revertants on the risk of virological failure of the first thymidine analog-containing highly active antiretroviral therapy (HAART).
  
  
  METHODS
  The study included 491 HIV-1 subjects of the Italian Cohort Naive for Antiretrovirals, 405 of whom received a genotypic assay before therapy and had a virological follow-up.
  
  
  METHODS
  Pre-treatment genotypic resistance was assessed by sequencing of the whole protease (PR) and reverse transcriptase (RT) region.
  
  
  RESULTS
  Three (3.2%) and 13 (3.3%) individuals with recent (n = 95) and chronic (n = 396) HIV-1 infection carried an HIV-1 strain with 215 revertants (215D/C/E/A/V), respectively. In contrast, nucleoside associated mutations were higher in the former (15.8%) compared with the latter group (6.8%) (P = 0.005). A multivariable regression model, considering pre-HAART viral load levels, use of saquinavir-hard gel as the only PI, use of zidovudine, number of other RT and PR mutations, indicated that patients carrying 215 revertants had an increased risk of virological failure compared with those not carrying such mutants (adjusted relative hazard = 2.97 95% confidence interval, 1.11-7.94, P = 0.03). Among patients with 215 revertants, who experienced virological failure, four out of seven showed the emergence of the 215Y resistant mutation. The probability of 215Y occurrence was different between patients carrying 215 revertants compared with those who did not carried these mutants (P = 0.006).
  
  
  CONCLUSIONS
  HIV-1 215 revertants with an increased ability for selecting 215Y mutation are associated with a higher risk of virological failure and may lead to the appearance of virus carrying 215Y/F mutation in vivo. These findings suggest that 215 revertant viruses may compromise the efficacy of the first thymidine analog-containing regimen.
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Violin
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Rossella
authors.initials: R
authors.lastname: Velleca
authors.forename: Antonella
authors.initials: A
authors.lastname: Vincenti
authors.forename: Salvatore
authors.initials: S
authors.lastname: D'Elia
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiodo
authors.forename: Florio
authors.initials: F
authors.lastname: Ghinelli
authors.forename: Ada
authors.initials: A
authors.lastname: Bertoli
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Mauro
authors.initials: M
authors.lastname: Moroni
authors.forename: Claudia
authors.initials: C
authors.lastname: Balotta
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D002908:Chronic Disease; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012008:Recurrence; D012307:Risk Factors; D013936:Thymidine / Q000031:analogs & derivatives; D017211:Treatment Failure
chemical_list: D013936:Thymidine