Page 72 - HIV/AIDS Guidelines

Acceptable Protease Inhibitor-Based Component

Atazanavir. UnboostedATVisgivenoncedailyandhasfeweradverseeffectsonlipidprofilesthanother
availablePIs.ThreestudiescomparedATV-basedcombinationregimenswitheitherNFV-orEFV-based
regimens.ThesestudiesestablishedthatATV400mgoncedailyandbothcomparatortreatmentshadsimilar
virologicefficacyinARV-naivepatientsafter48weeksoftherapy. 5,46,62-63

UnboostedATVmaybeanacceptableinitialtherapyforpatientswhenaonce-dailyregimenwithoutRTVis
desiredandforpatientswithunderlyingriskfactorsindicatingthathyperlipidemiamaybeparticularly
undesirable(C).ConcomitantuseofTDForEFVwithATVcanlowertheconcentrationsofATV.Therefore,
ATVshouldbeboostedwithRTVwhencoadministeredwiththesetwoagents.ATVrequiresacidicgastric
pHfordissolution.Thus,concomitantuseofdrugsthatraisegastricpH,suchasantacids,H2antagonists,
andPPIs,maysignificantlyimpairATVabsorption.PPIsshouldnotbeusedinpatientswhoaretaking
unboostedATV.H2antagonistsandantacidsshouldbeusedwithcautionandwithcarefuldoseseparation.
(SeeTables14and15a.)

Protease Inhibitor Component that May be Acceptable but Should be Used with
Caution
Ritonavir-Boosted Saquinavir. TheGEMINIstudycomparedSQV/r(1000/100mgtwicedaily)with
LPV/r,bothgiventwicedaily,incombinationwithTDF/FTCgivenoncedaily,in337ART-naive
participantswhoweremonitoredover48weeks.SimilarlevelsofviralsuppressionandincreasesinCD4
64
countswereseeninbotharms. Triglyceride(TG)levelswerehigherintheLPV/rarmthanintheSQV/r
arm.TheSQV/rregimenhasahigherpillburdenandrequirestwice-dailydosingand200mgofRTV.Ina
healthyvolunteerstudy,SQV/ruseattherecommendeddosewasassociatedwithincreasesinbothQTand
PRintervals.ThedegreeofQTprolongationwithSQV/rwasgreaterthanthatseenwithsomeotherboosted
PIsusedattheirrecommendeddoses.Rarecasesoftorsadesdepointesandcompleteheartblockhavebeen
reportedinpost-marketingsurveillance.Basedonthesefindings,anECGbeforeinitiationofSQV/ris
recommended.SQV/risnotrecommendedforpatientswithanyofthefollowingconditions:documented
congenitaloracquiredQTprolongation,pretreatmentQTintervalof>450milliseconds(msec),refractory
hypokalemiaorhypomagnesemia,completeatrioventricular(AV)blockwithoutimplantedpacemakers,at
42
riskofcompleteAVblock,orreceivingotherdrugsthatprolongQTinterval. Basedontheserestrictions
andbecausethereareseveralotherpreferredoralternativePIoptions,thePanelrecommendsthatSQV/r
maybeacceptablebutshouldbeusedwithcautioninselectedARV-naivepatients (C).

Integrase Strand Transfer Inhibitor-Based Regimens (Integrase Strand Transfer Inhibitor

+ Two Nucleoside Reverse Transcriptase Inhibitors)
Raltegravir. RALisanINSTIthatisapprovedforuseinART-naivepatientsonthebasisofresultsof
STARTMRK,aPhaseIIIstudythatcomparedRAL(400mgtwicedaily)withEFV(600mgoncedaily),eachin
combinationwithTDF/FTC,inART-naivesubjects.Thismultinationaldouble-blind,placebo-controlledstudy
enrolled563subjectswithplasmaHIV-1RNAlevels>5,000copies/mL.AtWeek48,asimilarpercentageof
subjectsachievedHIV-1RNAlevels<50copies/mLinbothgroups(86.1%and81.9%forRALandEFV,
3
respectively,P<0.001fornoninferiority).CD4countsroseby189cells/mm intheRALgroupversus163
3
6
cells/mm intheEFVgroup.Thefrequencyofseriousadverseeventswassimilarinbothgroups. At156weeks,
virologicandimmunologicresponsesremainedsimilarinbothgroupswithnonewsafetyconcernsidentified. 13
Onthebasisofthesedata,thePanelrecommendsRAL+TDF/FTC(or3TC)asapreferredregimenforART-
naivepatients(AI).Inasmallsingle-armpilotstudyof35subjectswhoreceivedaregimenofRAL+
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ABC/3TC,91%ofsubjectshadHIVRNAlevels<50copies/mLatWeek48. Onthebasisofthesepreliminary
data,RAL+ABC/3TCmaybeusedasanalternativeINSTI-basedregimen(BIII).RALusehasbeenassociated

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-11

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