Page 75 - HIV/AIDS Guidelines

betweenarmswasobservedregardlessofwhetherthethirdactivedrugwasEFVorATV/r.Therewasno
differencebetweenABC/3TCandTDF/FTCintimetovirologicfailureforparticipantswhohadplasmaHIV
RNA<100,000copies/mLatscreening.TDF/FTChasamorefavorablesafetyandtolerabilityprofilethan
ABC/3TC. 82
Inanotherstudy(HEAT),688participantsreceivedABC/3TCorTDF/FTCincombinationwithonce-daily
LPV/r.AsubgroupanalysisaccordingtobaselineHIVRNAof<100,000copies/mLor≥100,000copies/mL
yieldedsimilarpercentagesofparticipantswithHIVRNA<50copies/mLat96weeksforthetworegimens
(63%vs.58%forthosewhohad<100,000copies/mLand56%vs.58%forthosewhohad>100,000
71
copies/mL,respectively). TheASSERTstudycomparedopenlabelABC/3TCwithTDF/FTCin385HLA-
B*5701-negative,ART-naivepatients;allstudysubjectsalsoreceivedEFV.At48weeks,theproportionof
participantswithHIVRNA<50copieswasloweramongABC/3TC-treatedsubjects(59%)thanamong
TDF/FTCsubjects(71%)(difference11.6%,95%confidenceinterval[CI]:2.2–21.1). 83
ABChasthepotentialforseriousHSRs.ClinicallysuspectedHSRshavebeenobservedin5%to8%of
patientswhostartABC.TheriskofthisreactionishighlyassociatedwiththepresenceoftheHLA-B*5701
allele. 84-85 (SeeHLA-B*5701Screening.)HLA-B*5701testingshouldprecedeuseofABC.ABCshouldnot
begiventopatientswhotestpositiveforHLA-B*5701,andbasedontestresults,ABChypersensitivity
shouldbenotedonthepatient’sallergylist.PatientswhotestHLA-B*5701negativearelesslikelyto
experienceanHSR,buttheyshouldbecounseledaboutthesymptomsofthereaction.

AnassociationbetweenABCuseandMIwasfirstreportedintheD:A:Dstudy.Thislarge,multinational
observationalstudygroupfoundthatrecent(within6months)orcurrentuseofABC,butnotTDF,was
associatedwithanincreasedriskofMI,particularlyinparticipantswithpre-existingcardiacriskfactors. 40,86
SincethisD:A:Dstudy,multiplestudieshaveexploredthisassociation.Somestudieshavefoundan
association; 87-90 othershavefoundaweakassociationornoassociation. 41,91-94 Multiplestudieshavealso
beenconductedtoevaluatepotentialmechanisticpathways,includingendothelialdysfunction,increased
plateletreactivity,leukocyteadhesion,inflammation,andhypercoagulability 95-102 thatmayunderliethe
associationbetweenABCuseandanincreasedriskofMI.However,todate,noconsensuseitheronthe
associationofABCusewithMIriskorapossiblemechanismfortheassociationhasbeenreached.
Thefixed-dosecombinationofABC/3TCallowsforonce-dailydosing.Pendingadditionaldata,ABC/3TC
shouldbeusedwithcautioninindividualswhohaveplasmaHIVRNAlevels≥100,000copies/mLandin
personsathigherriskofCVD.However,thecombinationofABC/3TCremainsagoodalternativedual-
NRTIoptionforsomeART-naivepatients(BI).

Acceptable Dual Nucleoside Reverse Transcriptase Inhibitor
Zidovudine/Lamivudine (coformulated). Thedual-NRTIcombinationofZDV/3TChasextensive
durability,safety,andtolerabilityexperience. 3,5,8,22,103-105 Afixed-dosecombinationofZDV/3TCisavailable
forone-tablet,twice-dailydosing.Selectionofthe3TC-associatedM184Vmutationhasbeenassociated
withincreasedsusceptibilitytoZDV.InacomparativetrialofABC/3TCandZDV/3TC(bothgiventwice
dailyandcombinedwithEFV),eventhoughvirologicresponsesweresimilarinbotharms,theCD4count
increasewasgreaterintheABC/3TC-treatedpatientsthanintheZDV/3TC-treatedpatients. 81
Bonemarrowsuppression,manifestedbymacrocyticanemiaand/orneutropenia,isseeninsomepatients.
ZDValsoisassociatedwithGItoxicity,fatigue,andpossiblymitochondrialtoxicity,includinglactic
acidosis/hepaticsteatosisandlipoatrophy.BecauseZDV/3TChasgreatertoxicitythanTDF/FTCor
ABC/3TCandrequirestwice-dailydosing,thePanelrecommendsZDV/3TCasanacceptable,ratherthana
preferredoralternative,dual-NRTIoption (CI).

ZDV/3TCremainsapreferredoptioninpregnantwomen.ThisdualNRTIhasthemostPK,safety,and

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-14

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