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superiortoresponsetoLPV/r. Basedonthesedata,thePanelrecommendsDRV/r+TDF/FTCasa
preferredPI-basedregimen(AI).NorandomizedcontrolledtrialtoevaluatetheefficacyofDRV/rwithother
2-NRTIcombinationsexists.AsmallretrospectivestudysuggestedthatDRV/rplusABC/3TCmaybe
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effectiveintreatment-naivepatientsforupto48weeks. Basedonthispreliminaryinformation,thePanel
recommendsthiscombinationasanalternativePI-basedregimen(BIII).
Alternative Protease Inhibitor (in alphabetical order, by active protease inhibitor
component)

Ritonavir-Boosted Fosamprenavir (once or twice daily). FPV/risrecommendedasanalternativePI.The
KLEANtrialcomparedtwice-dailyFPV/rwithLPV/r,eachincombinationwithABCand3TC,inART-
naivepatients.AtWeeks48and144,similarpercentagesofsubjectsachievedviralloadsof<400
copies/mL. 53-54 Thefrequencyandseverityofadverseeventsdidnotdifferbetweentheregimens.Twice-
dailyFPV/rwasnoninferiortotwice-dailyLPV/r.Basedonthepreferenceforonce-dailyregimenswithno
morethan100mg/dayofRTV,twice-dailyFPVisnowconsideredanalternativechoice.

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Inastudycomparingonce-dailyFPV/r(1400mgwithRTV200mgoncedaily)withNFV, similarvirologic
efficacywasreportedinbotharms.Acomparativetrialofonce-dailyFPV/r(1400/100mg)withonce-daily
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ATV/r,bothincombinationwithTDF/FTC,wasconductedin106ARV-naiveparticipants. Similarvirologic
andCD4benefitswereseenwithbothregimens.Thesmallsamplesizeofthisstudyprecludestheassessment
ofsuperiorornoninferiorvirologicefficacyrequiredforapreferredPI.Collectively,FPV/rregimens,with
once-ortwice-dailydosing,arerecommendedasalternativePI-basedregimens.

Ritonavir-Boosted Lopinavir (coformulated). LPV/ristheonlyavailablecoformulatedboostedPI.Itcan
begivenonceortwicedaily.However,becausecomparedwithboostedPIsusingRTV100mg/day,LPV/r
mustbeboostedwith200mg/dayofRTVandisassociatedwithhigherratesofGIsideeffectsand
hyperlipidemia,LPV/risrecommendedasanalternativeratherthanpreferredPIforART-naivepatients.
EarlystudiesshowedthatLPV/rwassuperiortoNFVinmaintainingsuppressedviralloads. A7-year
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follow-upstudyofLPV/randtwoNRTIsshowedsustainedvirologicsuppressioninpatientswhowere
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maintainedontheoriginallyassignedregimen. ResultsofclinicaltrialsthatcomparedLPV/rwithATV/r,
DRV/r,FPV/r,orSQV/rarediscussedintherespectivesectionsofthisdocument.TheACTG5142study
showedthattheregimenoftwice-dailyLPV/rplustwoNRTIshaddecreasedvirologicefficacywhen
comparedwithEFVplustwoNRTIs.However,theCD4responsewasgreaterwithLPV/r,andtherewasless
drugresistanceassociatedwithvirologicfailure. 4

SeveraltrialshaveevaluateddifferentformulationsanddosagesofLPV/radministeredonceortwicedaily. 50,
59-60 Inthelargesttrialthatcomparedonce-dailywithtwice-dailyLPV/r,bothincombinationwithTDF/FTC,
664ART-naiveparticipantswererandomizedtoreceiveonce-ortwice-dailysoft-gelcapsulesoronce-or
twice-dailytabletsfor8weeks;atWeek8,allparticipantsreceivedthetabletformulationandmaintained
theirsamerandomizeddosingschedule. AtWeek48,77%ofonce-dailyand76%oftwice-dailyLPV/r
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recipientsachievedviralloads<50copies/mL.Ratesofmoderatetoseveredrug-relateddiarrheawere
similarbetweenthetwogroups.Inadditiontodiarrhea,majoradverseeffectsofLPV/rincludeinsulin
resistanceandhyperlipidemia,especiallyhypertriglyceridemia;theserequiredpharmacologicmanagementin
somepatients.IntheD:A:DandFrenchobservationalcohorts,cumulativeuseofLPV/rwasassociatedwith
aslightlyincreasedriskofMI. 40-41 Once-dailyLPV/rshouldnotbeusedinpatientswhohaveHIVmutations
associatedwithPIresistancebecausehigherLPVtroughlevelsmayberequiredtosuppressresistantvirus.
LPV/rgiventwicedailyisthepreferredPIforuseinpregnantwomen(A). Once-dailydosingshouldnotbe
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usedinpregnantwomen,especiallyduringthethirdtrimester,whenLPVlevelsareexpectedtodecline.For
moredetailedinformationregardingARTdrugchoicesandrelatedissuesinpregnancy,seetheperinatal
guidelines. 39

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-10

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