title: Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors.
abstract: BACKGROUND
  Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs.
  
  
  METHODS
  The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response.
  
  
  RESULTS
  One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively.
  
  
  CONCLUSIONS
  Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland. alexandra.scherrer@usz.ch
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Philippe
authors.initials: P
authors.lastname: Bürgisser
authors.forename: Christian
authors.initials: C
authors.lastname: Garzoni
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011760:Pyrrolidinones / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D016879:Salvage Therapy / Q000379:methods*
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium