title: Sequencing to NRTI plus NNRTI-only combinations after virological failure of protease inhibitor-based combination HIV-1 therapy.
abstract: OBJECTIVE
  To examine the success of sequencing to nucleoside reverse transcriptase inhibitor (NRTI) plus nonnucleoside reverse transcriptase inhibitor (NNRTI)-only combinations after virological failure of protease inhibitor (PI)-based combinations in NNRTI-naïve individuals.
  
  
  METHODS
  This was an observational cohort study.
  
  
  RESULTS
  171 patients were identified. The group was highly antiretroviral therapy-experienced with median cumulative NRTI and PI durations prior to change of 53 months and 21 months, respectively. The median CD4 count and viral load (VL) prior to change were 228 cells/mm(3) and 24500 copies/mL. Overall, 37.4% had a VL below the limit of detection (50 copies/mL) at 12 months (intention-to-treat analysis). Markers associated with success at 12 months were efavirenz (EFV) use, the use of three NRTI+NNRTI combinations, and abacavir (ABC) use. In multivariate analysis, use of EFV remained highly significant (relative hazard of virological success of nevirapine [NVP] vs. EFV = 0.39; p =.003), while ABC use became nonsignificant. A benefit from the use of three NRTI + NNRTI regimens was observed.
  
  
  CONCLUSIONS
  NRTI plus NNRTI-only combinations performed poorly, however the superior outcomes of patients treated with EFV are consistent with findings in cohort studies. The suggestion of benefit in patients receiving three NRTIs in addition to either NVP or EFV deserves further study in randomized trials.
authors.affiliation: Genitourinary Medicine, St Stephen's Centre, Chelsea and Westminster Hospital, London, United Kingdom. david.asboe@chelwest.nhs.uk
authors.forename: D
authors.initials: D
authors.lastname: Asboe
authors.forename: S
authors.initials: S
authors.lastname: Mandalia
authors.forename: B G
authors.initials: BG
authors.lastname: Gazzard
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors