Page 73 - HIV/AIDS Guidelines

withcreatinekinaseelevations.Myositisandrhabdomyolysishavebeenreported.Rarecasesofsevereskin
reactionsandsystemichypersensitivityreactions(HSRs)inpatientswhoreceivedRALhavebeenreported
duringpost-marketingsurveillanceoftheagent. 66

ComparisonsofRAL-basedregimensandboostedPI-basedregimensinART-naivesubjectshavenotbeen
reported.RALmustbeadministeredtwicedaily,apotentialdisadvantagewhencomparingRAL-based
regimenswithsomeotherregimens.RAL,likeEFV,hasalowergeneticbarriertoresistancethanRTV-
boostedPIs,andintheSTARTMRKcomparativetrial,resistancemutationswereobservedatapproximately
thesamefrequencyinRAL-andEFV-treatedparticipants.

CCR5 Antagonist-Based Regimens (CCR5-Antagonist + Two Nucleoside Reverse

Transcriptase Inhibitors)
TheMERITstudycomparedtheCCR5antagonistMVCwithEFV,bothincombinationwithZDV/3TC,ina
7
randomized,double-blindtrialinART-naiveparticipants. OnlyparticipantswhohadCCR5-tropicvirusand
hadnoevidenceofresistancetoanydrugsusedinthestudywereenrolled(n=721).At48weeks,virologic
suppression(definedasHIVRNA<400copies/mL)wasseenin70.6%ofMVCrecipientsandin73.1%of
EFVrecipients,andHIVRNAlevel<50copies/mLwasobservedin65.3%ofMVCrecipientsandin69.3%of
EFVrecipients.TheHIVRNA<50copies/mLresultsdidnotmeetthecriteriasetbytheinvestigatorsto
3
demonstratenoninferiorityforMVCinthisstudy.CD4countincreasedbyanaverageof170cells/mm inthe
3
MVCarmandby144cells/mm intheEFVarm.Through48weeks,comparedwithparticipantsreceiving
EFV,moreparticipantsdiscontinuedMVCbecauseoflackofefficacy(11.9%vs.4.2%),whereasfewer
participantsdiscontinuedMVCbecauseoftoxicity(4.2%vs.13.6%).Follow-upresultsat96weeks
67
demonstrateddurableresponsesforbothARVs. Inapost-hocreanalysisusingamoresensitiveviraltropism
assay,15%ofpatientswithnon-R5screeningviruswereexcludedfromanalysis,andtheirretrospective
exclusionresultedinsimilarresponseratesinbotharms,usingeithertheHIVRNAcriteriaof<400or<50
copies/mL.Basedontheresults,FDAapprovedMVCforuseinregimensforART-naivepatients.Because
MVCrequirestwice-dailydosing,requiresanexpensivetropismassaypriortouse,andexperiencewith
regimensotherthanZDV/3TCislimited,thePanelrecommendsMVC+ZDV/3TCasanacceptableregimen
foruseinART-naivepatients(CI).AlthoughtheMERITtrialusedZDV/3TCasitsNRTIbackbone,pending
furtherdata,manyclinicianswouldfavorthecombinationofMVCwithTDF/FTCorABC/3TC(CIII).

Dual-Nucleoside Reverse Transcriptase Inhibitor Options as Part of Initial Combination
Therapy

Summary: Dual-Nucleoside Reverse Transcriptase Inhibitor Components
DualNRTIsarecommonlyusedincombinationwithanNNRTI,aPI(usuallyboostedwithRTV),anINSTI,
oraCCR5antagonist.Mostdual-NRTIcombinationsusedinclinicalpracticeconsistofaprimaryNRTIplus
3TCorFTC.Both3TCandFTChavefewadverseeffectsbutmayselectfortheM184Vresistancemutation,
whichconfershigh-levelresistancetobothdrugs;amodestdecreaseinsusceptibilitytoddIandABC;and
improvedsusceptibilitytoZDV,d4T,andTDF. 68

AllNRTIsexceptddIcanbetakenwithorwithoutfood.Adherencemaybeadditionallyimprovedwith
once-dailydosing(availableforallNRTIsexceptd4TandZDV)andwithfixed-dosagecombinations,such
asABC/3TC,TDF/FTC(withorwithoutEFVorRPV),orZDV/3TC.
ThePanel’srecommendationsonspecificdual-NRTIoptionsaremadeonthebasisofvirologicpotencyand
durability,short-andlong-termtoxicities,thepropensitytoselectforresistancemutations,anddosing
convenience.

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-12

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