Page 66 - HIV/AIDS Guidelines

Non-Nucleoside Reverse Transcriptase Inhibitor- versus Protease Inhibitor- versus
Integrase Strand Transfer Inhibitor- versus CCR5 Antagonist-Based Regimens

Efavirenz(EFV)hasbeencomparedwithanumberofotherdrugs(otherNNRTIs,PIs,RAL,MVC)in
combinationregimenscontainingtwoNRTIs. 3-9 Todate,noregimenhasprovensuperiortoEFV-based
regimenswithrespecttovirologicresponses.

Non-Nucleoside Reverse Transcriptase Inhibitor- versus Protease Inhibitor-Based Regimens
RTV-boostedPI-basedregimenshaveshowngoodvirologicandimmunologicresponsesbutareoften
associatedwithmoregastrointestinal(GI)symptomsthanEFV-basedregimens,whichareassociatedwith
morerashandcentralnervoussystem(CNS)adverseeffects.Bothtypesofregimensmaybeassociatedwith
hepatictransaminaseelevations. 10
DrugresistancetomostPIsrequiresmultiplemutationsintheHIVproteasegeneandseldomdevelopsafter
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earlyvirologicfailure, especiallywhenRTVboostingisused.AtleastpartialresistancetoEFV,NVP,or
rilpivirine(RPV),however,isconferredbyasinglemutationinthereversetranscriptasegene,anditmay
developrapidlyaftervirologicfailure.Anestimated8%ofnewlyinfectedpatientsintheUnitedStatescarry
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NNRTI-resistantviruses. Becauseoftheconcernforprimaryresistanceintheantiretroviraltherapy(ART)-
naivepopulation,genotypictestingresultsshouldbeusedtoguidetheselectionoftheinitialARVregimen.(See
Drug-ResistanceTesting.)Intermsofconvenience,coformulationofEFV/tenofovir(TDF)/emtricitabine(FTC)
orRPV/TDF/FTCallowsforonce-dailydosingwithasingletablet.MostPI-basedregimensincludeRTV,may
bedosedonceortwicedaily,andhaveahigherpillburdenthanNNRTIregimens.Drug-druginteractionsare
importantwithbothkindsofregimens,butmoreclinicallysignificantinteractionsareseenwithRTV-boostedPI
regimensthanwithNNRTI-basedregimens.

Other Treatment Options
6
AnotheroptionforinitialtherapyisthecombinationofTDF/FTCandRAL. Thiscombinationshowed
virologicefficacysimilartothatofTDF/FTC/EFVupto156weeks andisgenerallywelltolerated.No
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clinicaltrialdatacomparingINSTI-basedwithPI-basedregimensexist.RALrequirestwice-dailydosing,
hasalowgeneticbarrierforselectionofresistancemutations,andhashadrelativelylimitedusewithother
dual-NRTIcombinations.MVChasbeenapprovedforuseinART-naivepatients,basedondatafromthe
MERITstudycomparingMVC/zidovudine(ZDV)/lamivudine(3TC)withEFV+ZDV/3TC. 7

ThediscussionsbelowfocusontherationaleforthePanel’srecommendations,basedontheefficacy,safety,
andothercharacteristicsofdifferentagentswithintheindividualdrugclasses.

Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens (One Non-Nucleoside
Reverse Transcriptase Inhibitor + Two Nucleoside Reverse Transcriptase Inhibitors)

Summary: Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens
FiveNNRTIs(delavirdine[DLV],EFV,etravirine[ETR],NVP,andRPV)arecurrentlyFDAapproved.

NNRTI-basedregimenshavedemonstratedvirologicpotencyanddurability.Themajordisadvantagesof
currentlyavailableNNRTIsinvolvetheprevalenceofNNRTI-resistantviralstrainsinART-naivepatients 12,
14-16 andthelowgeneticbarrierofNNRTIsfordevelopmentofresistance.Resistancetestingshouldbe
performedtoguidetherapyselectionforART-naivepatients(seeDrug-ResistanceTesting).AllNNRTIs
exceptforETRrequireonlyasinglemutationtoconferresistance,andcrossresistanceaffectingthese
NNRTIsiscommon.ETR,anNNRTIapprovedforART-experiencedpatients,hasinvitroactivityagainst
someviruseswithmutationsthatconferresistancetoDLV,EFV,andNVP. However,inRPV-treated
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patients,thepresenceofRPV-resistantmutationsatvirologicfailureiscommonandmayconfercross
resistancetoETR. 18

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-5

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