title: Negligible effect of tenofovir on atazanavir trough concentrations and genotypic inhibitory quotients in the presence and absence of ritonavir.
abstract: BACKGROUND
  It is recommended to boost atazanavir with ritonavir (ATV/r) when it is combined with tenofovir disoproxil fumarate (TDF) because of drug interactions. For tolerability, unboosted atazanavir (ATV) is sometimes coadministered with TDF. The objective of this study was to evaluate the impact of this interaction on the proportion of patients achieving target ATV C troughs and genotypic inhibitory quotients (GIQ).
  
  
  METHODS
  A therapeutic drug monitoring database was screened to evaluate ATV concentrations. Differences in C trough and GIQ values among 4 antiretroviral drug combinations were evaluated.
  
  
  RESULTS
  Three hundred eight C troughs, 91 GIQs, and 92 viral loads were evaluated for 238, 68, and 69 patients, respectively. Patients receiving ATV/r and TDF compared with ATV and TDF were more likely to have a therapeutic C trough (odds ratio, 2.27; 95% confidence interval: 1.46-3.52; P < 0.001). Among patients on unboosted ATV, the odds of having a therapeutic ATV C trough did not differ between groups with TDF versus without TDF. Although ritonavir increased the GIQ in patients receiving TDF (odds ratio, 3.38; 95% confidence interval: 1.30-8.81; P = 0.013), a similar proportion of patients on TDF and either ATV/r or ATV achieved a therapeutic GIQ.
  
  
  CONCLUSIONS
  In patients receiving TDF, ritonavir increased the ATV C trough and GIQ and patients on ATV/r were more likely to have therapeutic C troughs. However, among subjects without ritonavir boosting, TDF compared with other nucleosides did not influence the odds of achieving a therapeutic ATV C trough. These data suggest that ritonavir boosting of ATV is prudent, particularly in patients with resistance mutations.
authors.affiliation: Faculté de pharmacie, Université de Montréal, Montreal, Canada.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Fournier
authors.forename: Niamh
authors.initials: N
authors.lastname: Higgins
authors.forename: Réjean
authors.initials: R
authors.lastname: Thomas
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Baril
authors.forename: Denis
authors.initials: D
authors.lastname: Thibeault
authors.forename: Richard
authors.initials: R
authors.lastname: Lalonde
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sheehan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000069446:Atazanavir Sulfate; D004347:Drug Interactions / Q000235:genetics*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005838:Genotype; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D019438:Ritonavir / Q000494:pharmacology* / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load / Q000502:physiology
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir