Page 68 - HIV/AIDS Guidelines

orinwomenwithhighpregnancypotential(womenofchildbearingpotentialwhoaretryingtoconceiveor
whoaresexuallyactivewithmenandarenotusingeffectiveandconsistentcontraception)(AIII).

StudiesthatuseEFVanddual-NRTIcombinations(ABC,didanosine[ddI],d4T,TDF,orZDVtogetherwith
FTCor3TC)showdurablevirologicactivity,althoughtheremaybedifferencesamongthevarious
combinationschosen.(SeeDual-NucleosideReverseTranscriptaseInhibitorOptions.)Asingletablet
coformulatedwithTDF,FTC,andEFVprovidesone-tablet,once-dailydosingandiscurrentlythepreferred
NNRTI-basedregimen(AI).

Rilpivirine as Alternative Non-Nucleoside Reverse Transcriptase Inhibitor
Intwolarge,multinational,randomized,double-blindclinicaltrials,RPV(25mgoncedaily)wascompared
withEFV(600mgoncedaily),eachincombinationwithtwoNRTIs.Inapooledanalysisofthetwostudies,
83%ofRPV-treatedsubjectsand80%ofEFV-treatedsubjectshadplasmaHIVRNA<50copies/mLat48
weeks. 18,29-30 AlthoughoverallRPVdemonstratednoninferioritytoEFV,amongparticipantswithhigher
pretreatmentHIVRNA(>100,000copies/mL),virologicfailureoccurredmorefrequentlyinthose
randomizedtoreceiveRPV.SubjectswithvirologicfailureonRPVwerealsomorelikelytohavegenotypic
resistancetootherNNRTIs(EFV,ETR,andNVP)andtohaveresistancetotheirprescribedNRTIs.
DrugdiscontinuationsbecauseofadverseeffectsweremorecommonwithEFVthanwithRPV.The
frequencyofdepressivedisordersanddiscontinuationsduetodepressivedisordersweresimilarbetweenthe
twoarms,whereasdizziness,abnormaldreams,rash,andhyperlipidemiaweremorefrequentwithEFVthan
withRPV.
Athigherthantheapproveddoseof25mg,RPV(75mgoncedailyor300mgoncedaily)mayprolongthe
QTcinterval.Asaresult,RPVshouldbeusedcautiouslywhencoadministeredwithadrughavingaknownrisk
oftorsadesdepointes.AlthoughRPVhasshownnoteratogenicityinanimalstudies,dataonPKsandsafetyof
RPVinpregnantHIV-infectedwomenareinsufficientatthistime.RPVshouldnotbegiventoadolescents
youngerthan18yearsofagebecauseappropriatedosinginformationinthisagegroupislacking.

Afixed-dosecombinationtabletofRPV/TDF/FTCallowsforone-tabletonce-dailydosing.RPVmustbe
administeredwithameal.BecausetheoralbioavailabilityofRPVmaybesignificantlyreducedinthe
presenceofacid-loweringagents,theARVshouldbeusedwithcautionwithantacidsandH2receptor
antagonists.RPVusewithprotonpumpinhibitors(PPIs)iscontraindicated.Table15b providesguidanceon
thetimingofRPVadministrationwhentheagentisusedtogetherwithantacidsorH2receptorantagonists.

Basedonlimiteddataondurabilityoftreatmentresponses(48weeks)andthelowervirologicresponsetoRPV
comparedwithEFVinpatientswithhighpretreatmentviralloads,thepanelrecommendsRPV/TDF/FTCasan
alternativeregimenforinitialtherapy(BI).CautionshouldbeexercisedwhenusingRPVinpatientswith
plasmaHIVRNA>100,000copies/mL,giventhehigherRPVvirologicfailureratesandthegreaterprobability
ofETRresistanceatthetimeoffailureobservedinthispopulationduringclinicaltrials.

Nevirapine as Acceptable Non-Nucleoside Reverse Transcriptase Inhibitor
Inthe2NNtrial,70%ofparticipantsintheEFVarmand65.4%inthetwice-dailyNVParmhadvirologic
suppression(definedasHIVRNA<50copies/mL)at48weeks.Thisdifferencedidnotreachcriterianecessary
24
todemonstratenoninferiorityofNVP. TwodeathswereattributedtoNVPuse.Oneresultedfromfulminant
hepatitisandonefromstaphylococcalsepsisasacomplicationofStevens-Johnsonsyndrome(SJS).

IntheARTENtrial,ART-naiveparticipantswererandomizedtoNVP200mgtwicedailyorNVP400mgonce
dailyorRTV-boostedATV(ATV/r),allincombinationwithTDF/FTC.Theproportionofparticipantsineacharm
whoachievedtheprimaryendpointofhavingatleasttwoconsecutiveplasmaHIVRNAlevels <50copies/mL
beforeWeek48wassimilar(66.8%forNVPvs.65.3%forATV/r).However,moreparticipantsintheNVP

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-7

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