Page 67 - HIV/AIDS Guidelines

Onthebasisofclinicaltrialresultsandsafetydata,thePanelrecommendsthatEFV,RPV,orNVPmaybe
usedaspartofaninitialregimen.Inmostinstances,EFVispreferredonthebasisofitspotencyand
tolerability(asdiscussedbelow).EFVshouldnotbeusedinpregnantwomen(especiallyduringthefirst
trimester)orinwomenofchildbearingpotentialwhoareplanningtoconceiveorwhoaresexuallyactive
withmenandnotusingeffectiveandconsistentcontraception.
RPVmaybeusedasanalternativeNNRTIoptionintreatment-naivepatients,whereasNVPmaybeusedas
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anacceptableNNRTIoptioninwomenwithpretreatmentCD4counts≤250cells/mm orinmenwith
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pretreatmentCD4counts≤400cells/mm .(Seediscussionsbelow.)
AmongtheNNRTIs,DLVisdosedthreetimesdaily,hastheleastsupportiveclinicaltrialdata,andappears
tohavetheleastantiviralactivity.Assuch,DLVisnot recommended aspartofaninitialregimen(BIII).
ETRatadoseof200mgtwicedailyisapprovedforuseintreatment-experiencedpatientswithvirologic
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failure. Inasmall,randomized,double-blind,placebo-controlledtrial,ETR400mgoncedailywas
comparedwithEFV600mgoncedaily(bothincombinationwithtwoNRTIs)intreatment-naivesubjects.
Seventy-nineand78participantswererandomizedtotheETRandEFVarms,respectively.At48weeks,
76%oftheETRrecipientsand74%oftheEFVrecipientsachievedplasmaHIVRNA<50copies/mL.
NeuropsychiatricsideeffectsweremorefrequentlyreportedintheEFVrecipientsthanintheETR
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recipients. Theseresultssuggestthatonce-dailyETRmaybeapotentialNNRTIoptionintreatment-naive
patients.However,moredataarerequiredand,pendingresultsfromlargertrials,thepanelcannot
recommendETRasinitialtherapyatthistime.
FollowingisamoredetaileddiscussionofNNRTI-basedregimensforinitialtherapy.

Efavirenz as Preferred Non-Nucleoside Reverse Transcriptase Inhibitor

Largerandomized,controlledtrialsandcohortstudiesofART-naivepatientshavedemonstratedpotentviral
suppressioninEFV-treatedpatients;asubstantialproportionofthesepatientshadHIVRNA<50copies/mL
duringupto7yearsoffollow-up. 1-2,21 StudiesthatcomparedEFV-basedregimenswithotherregimens
demonstratedthatthecombinationofEFVwithtwoNRTIswassuperiorvirologicallytosomePI-based
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regimens,includingindinavir(IDV), ritonavir-boostedlopinavir(LPV/r), andnelfinavir(NFV) andto
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triple-NRTI–basedregimensofABC,ZDV,and3TCorABC,TDF,and3TC. 22-23 EFV-basedregimensalso
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hadvirologicactivitycomparabletothatofNVP-, 24-25 atazanavir(ATV)-, RAL-, orMVC-based regimens.
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TheACTG5142studyrandomizedpatientstoreceivetwoNRTIstogetherwitheitherEFVorLPV/r(oran
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NRTI-sparingregimenofEFVandLPV/r). Thedual-NRTIandEFVregimenwasassociatedwithabetter
virologicresponsethanthedual-NRTIandLPV/rregimenat96weeks,butthedual-NRTIwithLPV/r
regimenwasassociatedwithabetterCD4responseandlessdrugresistanceaftervirologicfailure.
The2NNtrialcomparedEFVwithNVP,bothgivenwithstavudine(d4T)and3TC,inART-naivepatients.
VirologicresponsesweresimilarforbothdrugsbutcomparedwithEFV,NVPwasassociatedwithgreater
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toxicityanddidnotmeetcriteriafornoninferiority. TworandomizedcontrolledtrialscomparedEFV+two
NRTIswithRPV+twoNRTIs.MostpatientsreceivedTDF/FTCastheNRTIpair.Pooleddataevaluatedat
48weeksdemonstratedcomparablevirologicefficacyforthetwostudygroups,exceptinparticipantsineach
groupwhohadbaselineHIVRNA>100,000copies/mL.Amongparticipantswhohadbaselineviremiaat
thislevel,agreaterproportionofsubjectsrandomizedtoRPVthantoEFVexperiencedvirologicfailure. 18

LimitationsofEFVareitsCNSadverseeffects,whichusuallyresolveoverafewweeks,anditspotential
teratogeniceffects.Inanimalreproductivestudies,EFVatdrugexposurelevelssimilartothoseachievedin
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humanscausedmajorcongenitalanomaliesintheCNSofnonhumanprimates. Inhumans,severalcasesof
neuraltubedefectsinnewbornsofmothersexposedtoEFVduringthefirsttrimesterofpregnancyhavebeen
reported. 27-28 Therefore,EFVisnotrecommendedinpregnantwomenduringthefirsttrimesterofpregnancy

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-6

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