Nevirapine or efavirenz for tuberculosis and HIV coinfected patients: exposure and virological failure relationship

Received 21 April 2014; returned 12 June 2014; revised 24 July 2014; accepted 6 August 2014Objectives:We describe nevirapine and efavirenz exposure on and off tuberculosis treatment and consequencesfor virological efficacy and tolerance in patients included in the ANRS 12146/12214-CARINEMO trial.Methods:Participants were randomly selected to receive either nevirapine at 200 mg twice daily ( n¼256) orefavir-enzat 600 mg daily (n¼270), both combined with two nucleoside analogues. Blood samples were drawn 12 h afternevirapine orefavirenzadministration, while on tuberculosistreatmentandafter tuberculosis treatment discontinu-ation.In 62 participants, samplestaken 12 h afterdrug administration were drawn weekly for the first monthof ART.Sixteen participants participated in an extensive pharmacokinetic study of nevirapine. Concentrations were com-pared with the therapeutic ranges of 3000–8000 ng/mL for nevirapine and 1000–4000 ng/mL for efavirenz.Results: Nevirapineconcentrations attheend ofthefirstweekof treatment (onantituberculosisdrugs) didnot differfrom concentrations off tuberculosis treatment, but declined thereafter. Concentrations at steady-state were4111 ng/mL at week 12 versus 6095 ng/mL at week 48 (P,0.0001). Nevirapine concentrations ,3000 ng/mLwere found to be a risk factor for virological failure. Efavirenz concentrations were higher on than off tuberculosistreatment (2700 versus 2450 ng/mL, P,0.0001).Conclusions: The omission of the 2 week lead-in dose of nevirapine prevented low concentrations at treatment ini-tiationbutdidnotpreventtheriskofvirologicalfailure.ResultssupporttheWHOrecommendationtouseefavirenzat600 mg daily in patients on rifampicin-based antituberculosis therapy.Keywords: TB/HIV coinfection, nevirapine, efavirenz, drug–drug interactions