title: Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens.
abstract: BACKGROUND
  The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments.
  
  
  METHODS
  We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3-6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression.
  
  
  RESULTS
  Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3-6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3-6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1-42.8), p<0.001).
  
  
  CONCLUSIONS
  The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring.
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: 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: Vincent
authors.initials: V
authors.lastname: Aubert
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Luigia
authors.initials: L
authors.lastname: Elzi
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 / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors