C Allavena1, E Dailly2, V Reliquet1, B Bonnet1, S Pineau3, E André-Garnier4, D Boutoille1, R Bouquié2, A Raveleau1, S Bouchez1, E Billaud5, F Raffi6. 1. Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France. 2. Clinical Pharmacology Department, CHU Hôtel Dieu, Nantes, France. 3. COREVIH Pays de la Loire, CHU Hôtel Dieu, Nantes, France. 4. Department of Virology, CHU Hôtel Dieu, Nantes, France. 5. Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France COREVIH Pays de la Loire, CHU Hôtel Dieu, Nantes, France. 6. Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France francois.raffi@wanadoo.fr.
Abstract
OBJECTIVES: 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. PATIENTS AND 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. CONCLUSION: 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.
OBJECTIVES: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-infectedpatients from nevirapine to rilpivirine. PATIENTS AND 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. CONCLUSION: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-infectedpatients on nevirapine wishing to simplify their regimen.
Authors: R Palacios; I A Pérez-Hernández; M A Martínez; M L Mayorga; C M González-Domenech; M Omar; J Olalla; A Romero; J M Romero; I Pérez-Camacho; J Hernández-Quero; J Santos Journal: Eur J Clin Microbiol Infect Dis Date: 2016-02-15 Impact factor: 3.267
Authors: Sean E Collins; Philip M Grant; Francois Uwinkindi; Annie Talbot; Eric Seruyange; Deborah Slamowitz; Adeline Mugeni; Eric Remera; Simon Pierre Niyonsenga; Josbert Nyirimigabo; Jean Paul Uwizihiwe; Pierre Dongier; Ribakare Muhayimpundu; Jean-Baptiste Mazarati; Andrew Zolopa; Sabin Nsanzimana Journal: Open Forum Infect Dis Date: 2016-07-01 Impact factor: 3.835