Page 69 - HIV/AIDS Guidelines

armsthanintheATV/rarmdiscontinuedstudydrugsbeforeWeek48becauseofadverseevents(13.6%vs.
2.6%,respectively)orlackofefficacy(8.4%vs.1.6%,respectively).NNRTI-and/orNRTI-resistance
mutationswereselectedin29of44(65.9%)participantswhoexperiencedvirologicfailurewhileonNVP,
whereasresistancemutationswerenotdetectedinanyofthe28participantswhohadvirologicfailureon
ATV/r. 31
SerioushepaticeventshavebeenobservedwhenNVPwasinitiatedinART-naivepatients.Theseevents
generallyoccurwithinthefirstfewweeksoftreatment.Inadditiontoexperiencingelevatedserum
transaminases,approximatelyhalfofthepatientsalsodevelopskinrash,withorwithoutfeverorflu-like
symptoms.RetrospectiveanalysisofreportedeventssuggeststhatwomenwithhigherCD4countsappearto
beathighestrisk. 31-33 A12-foldhigherincidenceofsymptomatichepaticeventswasseeninwomen
3
(includingpregnantwomen)withCD4counts>250cells/mm atthetimeofNVPinitiationthaninwomen
3
withCD4counts≤250cells/mm (11.0%vs.0.9%,respectively).Anincreasedriskwasalsoseeninmen
withpretreatmentCD4counts>400cells/mm comparedwithmenwithpretreatmentCD4counts≤400
3
cells/mm (6.3%vs.1.2%,respectively).Mostofthesepatientshadnoidentifiableunderlyinghepatic
3
abnormalities.Insomecases,hepaticinjuriescontinuedtoprogressdespitediscontinuationofNVP. 33-34 In
contrast,otherstudieshavenotshownanassociationbetweenbaselineCD4countsandsevereNVP
hepatotoxicity. 35-36 Symptomatichepaticeventshavenotbeenreportedwithsingle-doseNVPgivento
mothersorinfantsforpreventionofperinatalHIVinfection.

Onthebasisofthesafetyandefficacydatadiscussedabove,thePanelrecommendsthatNVPbeconsidered
asanacceptableNNRTI(C) asinitialtherapyforwomenwithpretreatmentCD4counts≤250cells/mm or
3
3
inmenwithpretreatmentCD4counts≤400cells/mm .PatientswhoexperienceCD4countincreasesto
levelsabovethesethresholdsasaresultofNVP-containingtherapycansafelycontinuetherapywithoutan
increasedriskofadversehepaticevents. 37
AttheinitiationofNVP,a14-daylead-inperiodatadosageof200mgoncedailyshouldbeinstitutedbefore
increasingtothemaintenancedosageof400mgperday(asanextended-release400-mgtabletoncedailyor
200-mgimmediate-releasetablettwicedaily).Someexpertsrecommendmonitoringserumtransaminasesat
baseline,at2weeks,then2weeksafterdoseescalation,andthenmonthlyforthefirst18weeks.Clinicaland
laboratoryparametersshouldbeassessedateachvisit.

Protease Inhibitor-Based Regimens (Ritonavir-Boosted or Unboosted Protease Inhibitor
+ Two Nucleoside Reverse Transcriptase Inhibitors)

Summary: Protease Inhibitor-Based Regimens
PI-basedregimens(particularlywithRTV-boosting)havedemonstratedvirologicpotencyanddurabilityin
treatment-naivesubjects.UnlikewithNNRTI-andINSTI-basedregimens,withPI-basedregimensresistance
mutationsareseldomdetectedatvirologicfailure.Inpatientswhoexperiencevirologicfailurewhileontheir
firstPI-basedregimen,fewornoPImutationsaredetectedatfailure. 31,38 EachPIhasitsownvirologic
potency,adverseeffectprofile,andpharmacokinetic(PK)properties.Thecharacteristics,advantages,and
disadvantagesofeachPIarelistedinTable6 andAppendixB,Table3.WhenselectingaboostedPI-based
regimenforanART-naivepatient,cliniciansshouldconsiderfactorssuchasdosingfrequency,food
requirements,pillburden,dailyRTVdose,druginteractionpotential,toxicityprofileoftheindividualPI,
andbaselinelipidprofileandpregnancystatusofthepatient.(Seetheperinatalguidelines forspecific
39
recommendationsinpregnancy ).
Anumberofmetabolicabnormalities,includingdyslipidemiaandinsulinresistance,havebeenassociated
withPIuse.ThecurrentlyavailablePIsdifferintheirpropensitytocausethesemetaboliccomplications,
whicharealsodependentonthedoseofRTVusedasaPKboostingagent.Twolargeobservationalcohort

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents F-8

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