title: Switching from tenofovir/emtricitabine and nevirapine to a tenofovir/emtricitabine/rilpivirine single-tablet regimen in virologically suppressed, HIV-1-infected subjects.
abstract: OBJECTIVE
  Nevirapine is an inducer of hepatic metabolism. After discontinuation, nevirapine has an inductive effect on cytochrome P450 3A4, which persists for a few weeks and which, after switching to rilpivirine, may reduce rilpivirine exposures and have a negative clinical impact. This study evaluates the virological outcome, pharmacokinetics and safety of switching virologically suppressed, HIV-1-infected patients from nevirapine to rilpivirine.
  
  
  METHODS
  This 24 week open-label single-centre study included HIV-1-infected adults with HIV-1 RNA <50 copies/mL for >6 months on tenofovir/emtricitabine and nevirapine, who were willing to simplify their regimen to tenofovir/emtricitabine/rilpivirine. Virological suppression, safety and nevirapine and rilpivirine pharmacokinetics were assessed.
  
  
  RESULTS
  At weeks 12 and 24, all 32 subjects remained virologically suppressed. One subject discontinued at week 1 for rilpivirine-associated insomnia and two patients chose to resume tenofovir/emtricitabine and nevirapine after week 12 because of rilpivirine-associated food constraint. There was no grade 3/4 laboratory abnormality. Rilpivirine trough concentrations were above the mean trough concentrations observed in Phase 3 studies by 1 week post-switch. Twenty-seven out of 32 patients had no measurable levels of nevirapine by 2 weeks post-switch. The meal accompanying tenofovir/emtricitabine/rilpivirine intake satisfied food requirements in 81% of cases. Overall general satisfaction was improved in 90% of the subjects despite food constraints.
  
  
  CONCLUSIONS
  Nevirapine has a short and limited inductive effect on rilpivirine metabolism, which is not clinically significant. Tenofovir/emtricitabine/rilpivirine is an efficacious and safe option for virologically suppressed HIV-infected patients on nevirapine wishing to simplify their regimen.
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Allavena
authors.affiliation: Clinical Pharmacology Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: E
authors.initials: E
authors.lastname: Dailly
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: V
authors.initials: V
authors.lastname: Reliquet
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Bonnet
authors.affiliation: COREVIH Pays de la Loire, CHU Hôtel Dieu, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Pineau
authors.affiliation: Department of Virology, CHU Hôtel Dieu, Nantes, France.
authors.forename: E
authors.initials: E
authors.lastname: André-Garnier
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: D
authors.initials: D
authors.lastname: Boutoille
authors.affiliation: Clinical Pharmacology Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: R
authors.initials: R
authors.lastname: Bouquié
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Raveleau
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Bouchez
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France COREVIH Pays de la Loire, CHU Hôtel Dieu, Nantes, France.
authors.forename: E
authors.initials: E
authors.lastname: Billaud
authors.affiliation: Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France francois.raffi@wanadoo.fr.
authors.forename: F
authors.initials: F
authors.lastname: Raffi
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D057915:Drug Substitution; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage; D009570:Nitriles / Q000008:administration & dosage; D063065:Organophosphonates / Q000008:administration & dosage; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage; D000068696:Rilpivirine; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D004338:Drug Combinations; D009570:Nitriles; D063065:Organophosphonates; D011743:Pyrimidines; D003841:Deoxycytidine; D019829:Nevirapine; D000068698:Tenofovir; D000068696:Rilpivirine; D000068679:Emtricitabine; D000225:Adenine
keywords: antiretroviral therapy; genotypes; non-nucleoside reverse transcriptase inhibitors; pharmacokinetic interactions