Allavena C, Dailly E, Reliquet V, Bonnet B, Pineau S, André-Garnier E, Boutoille D, Bouquié R, Raveleau A, Bouchez S, Billaud E, Raffi F
Infectious Diseases Department, CHU Hôtel Dieu, Nantes, France.
Clinical Pharmacology Department, CHU Hôtel Dieu, Nantes, France.
J Antimicrob Chemother. 2014 Oct;69(10):2804-8. doi: 10.1093/jac/dku187. Epub 2014 Jun 6.
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.
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.
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.
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.
奈韦拉平是肝脏代谢的诱导剂。停药后，奈韦拉平对细胞色素P450 3A4有诱导作用，这种作用会持续数周，在换用利匹韦林后，可能会降低利匹韦林的血药浓度并产生负面临床影响。本研究评估了病毒学抑制的HIV-1感染患者从奈韦拉平换用利匹韦林后的病毒学转归、药代动力学和安全性。
这项为期24周的开放标签单中心研究纳入了接受替诺福韦/恩曲他滨和奈韦拉平治疗且HIV-1 RNA<50拷贝/mL超过6个月的HIV-1感染成人，他们愿意将治疗方案简化为替诺福韦/恩曲他滨/利匹韦林。评估了病毒学抑制情况、安全性以及奈韦拉平和利匹韦林的药代动力学。
在第12周和第24周，所有32名受试者均保持病毒学抑制。1名受试者在第1周因利匹韦林相关的失眠而停药，2名患者在第12周后因利匹韦林相关的食物限制选择重新使用替诺福韦/恩曲他滨和奈韦拉平。没有3/4级实验室异常。换用利匹韦林1周后，利匹韦林谷浓度高于3期研究中观察到的平均谷浓度。32名患者中有27名在换用利匹韦林2周后奈韦拉平检测不到。81%的情况下，与替诺福韦/恩曲他滨/利匹韦林一起摄入的餐食满足食物要求。尽管存在食物限制，但90%的受试者总体满意度有所提高。
奈韦拉平对利匹韦林代谢的诱导作用短暂且有限，在临床上无显著意义。对于希望简化治疗方案的、接受奈韦拉平治疗且病毒学抑制的HIV感染患者，替诺福韦/恩曲他滨/利匹韦林是一种有效且安全的选择。
