Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIVTB co-infected Thai adults.docVIP

Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIVTB co-infected Thai adults.doc

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Uttayamakuletal.AIDSResearchandTherapy2010,7:8 /content/7/1/8 RESEARCH OpenAccess EffectsofCYP2B6G516Tpolymorphismson plasmaefavirenzandnevirapinelevelswhen co-administeredwithrifampicininHIV/TB co-infectedThaiadults SumonmalUttayamakul1,2,SiriratLikanonsakul2,WeerawatManosuthi2,NuanjunWichukchinda3, ThareeratKalambaheti1,EmiENakayama4,TatsuoShioda4,SrisinKhusmith1* Abstract Background:CytochromeP4502B6(CYP2B6)metabolizesefavirenzandnevirapine,themajorcoreantiretroviral drugsforHIVinThailand.Rifampicin,acriticalcomponentoftuberculosis(TB)therapyisapotentinducerofCYP enzymeactivity.PolymorphismsofCYP2B6andCYP3A4areassociatedwithalteredactivityofhepaticenzymein theliverandpharmacokineticsresultingintreatmentefficacy.ThisstudyaimedtoinvestigatewhetherCYP2B6or CYP3A4polymorphismshadeffectsonplasmaefavirenzandnevirapineconcentrationswhenco-administeredwith rifampicininHIV/TBco-infectedThaiadults. Results:Westudied124rifampicinrecipientswithconcurrentHIV-1/TBcoinfection,receivingefavirenz(600mg/ day)(n=65)ornevirapine(400mg/day)(n=59)basedantiretroviraltherapy(ART).ThefrequenciesofGG,GTand TTgenotypesofCYP2B6-G516Twere38.46%,47.69%and13.85%inefavirenzgroupand44.07%,52.54%and3.39% innevirapinegroup,respectively.Themean12-hourpost-doseplasmaefavirenzconcentrationinpatientswithTT genotypeatweeks6and12ofARTand1monthafterrifampicindiscontinuation(10.97±2.32,13.62±4.21and 8.48±1.30mg/L,respectively)weresignificantlyhigherthanthosewithGT(3.43±0.29,3.35±0.27and3.21± 0.22mg/L,respectively)(p0.0001)orGGgenotypes(2.88±0.33,2.45±0.26and2.08±0.16mg/L,respectively) (p0.0001).Likewise,themean12-hourpost-doseplasmanevirapineconcentrationinpatientscarryingTT genotypeatweeks6and12ofARTand1monthafterrifampicindiscontinuation(14.09±9.49,7.94±2.76and 9.44±0.17mg/L,respectively)tendedtobehigherthanthosecarryingGT(5.65±0.54,5.58±0.48and7.03± 0.64mg/L,respectively)orGGgenotypes(5.42±0.48,5.34±0.50and6.43±0.64mg/L,respectively)(p=0.003, p=0.409andp=0.448,respectively).ComparedwiththeeffectsofCY

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