Page 74 - HIV/AIDS Guidelines

Preferred Dual-Nucleoside Reverse Transcriptase Inhibitor

Tenofovir/Emtricitabine (coformulated). TDFisanucleotideanalogwithpotentactivityagainstbothHIV
andhepatitisBvirus(HBV)andwithalongintracellularhalf-lifethatallowsforonce-dailydosing.The
fixed-dosecombinationsofTDF/FTCandTDF/FTC/EFVarebothadministeredasonetabletoncedailyand
aredesignedtoimproveadherence.

TDF,whenusedwitheither3TCorFTCaspartofanEFV-basedregimeninART-naivepatients,
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demonstratedpotentvirologicsuppression andwassuperiortoZDV/3TCinvirologicefficacyupto144
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weeks. Inthe934study,moreparticipantsintheZDV/3TCarmthanintheTDF/FTCarmdevelopedloss
oflimbfat(asassessedbydual-energyx-rayabsorptiometry[DXA])andanemiaat96and144weeks. 69
EmergenceoftheM184VmutationwaslessfrequentwithTDF/FTCthanwithZDV/3TC,andnoparticipant
haddevelopedtheK65Rmutationafter144weeksoftherapy,incontrasttootherstudiesinwhichTDFwas
combinedwith3TC.TDFwithFTCor3TCincombinationwithseveralboostedPIsandRALhasbeen
studiedinrandomizedclinicaltrials;allsuchtrialsdemonstrategoodvirologicbenefit. 6,47,50,56,60

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TDF/FTCwascomparedwithABC/3TCintheACTG5202study andtheHEATtrial. Inferiorvirologic
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responseswereobservedinparticipantsrandomizedtoABC/3TCwhohadapretreatmentHIVRNA
>100,000copies/mL.ThiswasnotconfirmedbytheresultsfromtheHEATtrial.(SeetheABC/3TC section
formoredetaileddiscussion.)

Renalimpairment,manifestedbyincreasesinserumcreatinine,glycosuria,hypophosphatemia,andacute
tubularnecrosis,withTDFusehasbeenreported. 72-73 RiskfactorsmayincludeadvancedHIVdisease,
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greatertreatmentexperience,andpre-existingrenalimpairment. Renalfunction,urinalysis,andelectrolytes
shouldbemonitoredinpatientswhoareonTDF.Inpatientswhohavesomedegreeofpre-existingrenal
insufficiency(creatinineclearance[CrCl]<50mL/min),TDFdosageadjustmentisrequired.(SeeAppendix
B,Table7 fordosagerecommendations.)However,becauseavailabledosageadjustmentguidelinesforrenal
dysfunctionarebasedonPKstudiesonlyandnotonsafetyandefficacydata,theuseofalternativeNRTIs
(especiallyABC)maybepreferredoverdose-adjustedTDFinthissetting.
ConcomitantuseofsomePIscanincreaseTDFconcentrations,andstudieshavesuggestedagreaterriskof
renaldysfunctionwhenTDFisusedinPI-basedregimens. 72,75-78 TDFhasbeenusedincombinationwithPIs
withoutrenaltoxicityinseveralclinicaltrialsthatinvolvedpatientswhohadCrCl>50to60mL/min.
Furthermore,intworandomizedstudiescomparingTDF/FTCwithABC/3TC,participantsreceiving
TDF/FTCexperiencedasignificantlygreaterdeclineinbonemineraldensity. 79-80
TDFpluseitherFTCor3TCisthepreferredNRTIcombination,especiallyforpatientscoinfectedwithboth
HIVandHBVbecausethesedrugshaveactivityagainstbothviruses.TheuseofasingleHBV-activeNRTI
(e.g.,3TCorFTC)canleadtoHBVresistanceandisnotrecommended.(SeeHIV/HepatitisBCoinfection.)
Alternative Dual Nucleoside Reverse Transcriptase Inhibitor

Abacavir/Lamivudine (coformulated) for Patients who Test Negative for HLA-B*5701.
InacomparativetrialofABC/3TCandZDV/3TC(bothgiventwicedailyandcombinedwithEFV),
participantsfrombotharmsachievedsimilarvirologicresponses.CD4T-cellincreaseat48weekswas
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greaterintheABC-treatedparticipantsthanintheZDV-treatedparticipants. TheACTG5202study,a
randomizedcontrolledtrialinmorethan1,800participants,evaluatedtheefficacyandsafetyofABC/3TC
versusTDF/FTCwhenusedincombinationwitheitherEFVorRTV-boostedATV.Treatmentrandomization
wasstratifiedonthebasisofascreeningHIVRNAof<100,000copies/mLor>100,000copies/mL.HLA-
B*5701testingwasnotrequiredpriortostudyentry,whichmayhaveinfluencedtheresultsofthetrialwith
respecttosomeofthesafetyandtolerabilityendpoints.ADataSafetyMonitoringBoardrecommendedearly
terminationofthe>100,000copies/mLstratificationgroupbecauseofasignificantlyshortertimetostudy-
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definedvirologicfailureintheABC/3TCarmthanintheTDF/FTCarm. Thisdifferenceinvirologicfailure
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-13

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