title: Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA.
abstract: OBJECTIVE
  To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens.
  
  
  METHODS
  NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) with genotypic resistance test results available at time of initiation (baseline). Virological failure was defined as two consecutive values > 500 copies/ml after starting the regimen. Cox models were used to investigate time to virological failure (the first of two values).
  
  
  RESULTS
  A total of 759 patients were included (13% antiretroviral-naive): 389 initiated NVP and 370 initiated EFV. Baseline IAS-USA NNRTI resistance mutations were detected in 3%. Using the Rega algorithm (version 7.1) to interpret resistance, 460 (64%) patients had resistance (full or intermediate) to at least one drug they were starting (69% NVP, 60% EFV, P = 0.011); 287 (74%) NVP and 168 (45%) EFV patients experienced virological failure after treatment initiation, P < 0.001. After adjustment for previous antiretroviral use, previous AIDS, year started NNRTI, CD4 cell count (baseline, nadir), viral load (baseline, maximum), and baseline drug resistance (measured by Rega), the relative hazards (EFV versus NVP) of virological failure was 0.50, 95% confidence interval: 0.39-0.65, P < 0.001. At time of virological failure, comparable levels of NNRTI resistance were detected. The K103N mutation emerged more in patients failing EFV and Y181C in patients failing NVP.
  
  
  CONCLUSIONS
  NVP may be associated with an inferior virological outcome compared to EFV in NNRTI-naive patients with extensive resistance to other drug classes. The profile of NNRTI resistance mutations when virologically failing an NNRTI-containing regimen appears to depend on the NNRTI the patients fail.
authors.affiliation: Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK. w.bannister@pcps.ucl.ac.uk
authors.forename: Wendy P
authors.initials: WP
authors.lastname: Bannister
authors.forename: Lidia
authors.initials: L
authors.lastname: Ruiz
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Clive
authors.initials: C
authors.lastname: Loveday
authors.forename: Anders
authors.initials: A
authors.lastname: Karlsson
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics*; D005060:Europe; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz