e/c/f/taf single tablet regimen for post-exposure prophylaxis · 2019-03-10 · id# 0985 study...

ID#0985

Studysettingsanddesign:Prospective,open-label,single-armtrialin15Frenchcenters(NCT02998320).Individualsaged≥18yearswithpotentialHIVexposure(occupationalornot)intheprevious48hourswhometcriteriaforPEPinitiationreceivedonce-dailyE/C/F/TAFfor28days.Assessments: The primary endpoint was PEP completion at day 28, excluding withdrawal after sourcepatientwastestednegativetoHIV.Secondaryendpointswere:(1)  Adherence:throughselfreport[day14and28]andelvitergavirbloodplasmalevel[day14](2)  Qualityoflife:throughSF-12questionnaire[baseline,day14and28],(3)  Safety: throughquestionnaire [day14and28]andbiologicalparameters (creatinine,GFR,AST,ALT,

phosphate)[baseline,day14and28](4)  Efficacy:throughHIVserology[baseline,day56and112]

Introduction:HIV post-exposure prophylaxis (PEP) completion rates are ofmajor concern, as rates ofindividualscompletingthe28-dayscourseregimenrangefrom56%to78%.Recently, theelvitegravir/cobicistat/emtricitabine/tenofoviralafenamidecoformulation(E/C/F/TAF)wasapprovedforHIVinfectiontreatment.Thissingletabletregimen(STR)containsanewprodrug,tenofoviralafenamide,whichcouldimprovethesafetyprofileoftenofovir[10].

Objectives:TodescribePEPcompletionandsafetyofanE/C/F/TAFregimen.

Self-reported adherence was100%, between 90 and 99%, and<90% for 76%, 22% and 2% ofindividualsatday14;andfor75%,17% and 8% of individuals at day28,respectively(p>0.05)(seeFigureA)Median e lv i tegrav i r t roughconcentrationatday14was0.628mg/L (range, 0-4.201), thereforeabove 0.190 mg/L for 88% ofparticipants(seeFigureB)

Background

Methods

Treatmentoutcomes

Adherence

Safety

Overall, 226 adverse events were reported in 58 (68%) and 43 (59%) participants, at day 14 and 28respectively(p>0.05).

At day 14; 93, 24 and 8 grade 1, 2 and 3 adverse eventswere observed, and 73, 21 and 7 on day 28,respectively (p>0.05). Themost frequent reported adverseeventswere asthenia (19%), abdominal pain(16%),diarrhea(15%)andheadache(14%).Norenalorliverabnormalitiesoccurred.

Non-significantvariationsincreatinine,GFR,AST,ALTandphosphatelevelswereobserved(seeFigure)

Conclusions

81 % of individuals (95% CI, 73-89)completed PEP course till day 28 visit(n=78).Completion failure (n=18,19%)wasdueto:-losttofollow-up(n=16)-individual’sownchoice(n=1)-withdrawalofconsent(n=1)

No PEP interruption due to adverse eventswasdocumented

14 additional participants (16%) were alsolost to follow-up between day 28 to day112, and pre-exposure prophylaxis wasinitiatedfor1participant(seeFigure)

NoHIVseroconversionwasobserved

ThePEPcompletionratewasof81%,thusintherangeofotherrecentlyapprovedSTRwhenusedinaPEPsetting.PEPnon-completionwasnotdirectlyattributedtoE/C/F/TAF,butmostlytolossesoffollow-up,whichfrequentlyhampersPEPcare.Wealsoreporta100%efficacyrate,asnoparticipantwassubsequentlytestedHIVpositiveonstudy.Highadherence(>90%ofpillsintake)totheE/C/F/TAFregimenwasdocumentedbybothself-reportsin98%and92%atday14and28respectively,aswellasbypharmacologicalassessments(appropriatein88%ofcases).TheseresultsweresimilarthanthoseobtainedwithotherPEPSTR.QualityoflifemeasureswerenotmodifiedonE/C/F/TAFandweresimilarthanthoseofthegeneralpopulation,suggestingthatE/C/F/TAFissuitableforfurtherPEPusage.Although,noPEPdiscontinuationsduetosafetyreasonsweredocumented,evenifadverseeventsrateswerehigherinPEPusersthaninHIV-infectedindividuals.Whencomparingtootherintegraseinhibitors-basedPEPregimen,E/C/F/TAFshowedsimilarcompletionratesastheotherelvitegravir-basedanddolutegravir.Thisresultcouldbefurtherexplainedbylowratesofadverseeventswiththesecompounds.Overall,PEPE/C/F/TAFshowedanacceptablesafetyprofileandgoodcompletionrates.Self-reportedanddruglevelsindicatedgoodadherence,confirmingthatE/C/F/TAFcouldbearegimenofchoiceforPEP.

Funding:GileadSciencesinc.

ResultsAllpatientsachievedormaintainedviralsuppressionHIV-RNA<50copies/mLfromweeks4to48Results

StudyparticipantsandStudyFlowchart

96individualswereincluded:-NoHIVpositivetestoractiveHBVorHCVatbaseline-6syphilisatinitialscreeningParticipantswereprimarilymale(n=75,77%)withamedianageof31years(range,18-69)ExposurestoHIVwere:-8occupational-88sexual,ofwhich64%wereMSMand47%wereunprotectedSixsourcepatientswereknowntobeHIV-infected(noHIV-RNAavailable)

E/C/F/TAFSINGLETABLETREGIMENFORPOST-EXPOSUREPROPHYLAXISGANTNERPierre1,HESSAMFARMojgan2,SOUALAMohamedFaouzi3,VALINNadia4,SIMONAnne5,AJANAFaiza6,BOUVETElisabeth7,ROUVEIXElisabeth8,COTTELaurent9,BANI-SADRFirouzé10,HUSTACHE-MATHIEULaurent11,LEBRETTEMarie-Gisèle12,MURETPatrice13;REYDavid14fortheE/C/F/TAFPEPStudyGroup.1 Laboratory ofMolecular Virology,HôpitauxUniversitaires de Strasbourg, Strasbourg; 2Médecine Interne etMaladies Infectieuses,Hôpital SaintAndré, CHUdeBordeaux, Bordeaux; 3Maladies Infectieuses et Tropicales, CHUPontchaillou, Rennes; 4Maladies infectieuses ettropicales,HôpitalSaint-Antoine,APHP,Paris;5MédecineInterneetImmunologieClinique,HôpitalPitié-Salpêtrière,APHP,Paris;6MaladiesInfectieusesetduVoyageur,CentreHospitalierdeTourcoing,Tourcoing;7MaladiesInfectieuses,HôpitalBichat,APHP,Paris;8MédecineInterne,HôpitalAmbroiseParé,APHP,Paris;9MaladiesInfectieusesetTropicales,HôpitaldelaCroixRousse,Lyon;10MaladiesInfectieusesetTropicales,HôpitalRobertDebré,Reims;11MaladiesInfectieusesetTropicales,HôpitalJeanMinjoz,Besançon;12MaladiesInfectieusesetTropicales,HôpitalTenon,APHP,Paris;13Laboratoiredepharmacologieclinique,INSERM,UMR1098,HôpitalJeanMinjoz,Besançon;14LeTraitd’Union,HIV-infectioncarecenter,HôpitauxUniversitairesdeStrasbourg,Strasbourg.

Health-relatedqualityoflife

Mean quality of life SF-12 measuresofphysicalandmentalhealthwereof50 (range, 27-64) and 47 (range,17-65) at baseline, 52 (range, 25-64)and48(range,25-67)onday14,and51 (range, 28-61) and 49 (range,22-61) on day 28, respectively(p>0.05)(seeFigure)

Correspondingauthor:

PierreGantner,LaboratoiredeVirologie,3,rueKoeberlé,67000Strasbourg,France.

pierre.gantner@icloud.com

PEPCompletionfailure(n=18)16losttofollow-up1consentwithdrawal

1stoppedPEPaspersonalchoice

96individualsincluded

101screenedindividualseligibleforPEP

Exclusions(n=5)3individualsdidnotreceivedatleastonedoseofE/C/F/TAF2sourcepatientwerefurther

testedHIV-negative

78individualscompletedPEPtillday28

TimeD0 D56 D112D28D14

96

8078

65 63

E/C/F/TAF

ParticipantsonPEP/follow-up(n)

TimeD28D14

8078

90-99%

Selfrepo

rted

adh

eren

ce(n

)

<90%

100%

A NS

D14

Elvitegravirtrou

ghlevels(m

g/L)

B

0

1

2

3

4

physical

mental

SF-12score

TimeD0 D14 D28

NS

5045

55

Creatin

ine(μmol/L)

020406080100120140

D0 D280

0,5

1

1,5

D0 D28020406080100120140

D0 D28020406080100120140

D0 D280

20406080100120140

D0 D28

GFR(m

L/min)

AST(IU

/L)

ALT(IU

/L)

Phosph

ate(m

mol/L)

E/C/F/TAFPEPStudyGroupBesançon:Hustache-Mathieu,Laurent;Muret,Patrice;Bordeaux:Hessamfar,Mojgan;Boulogne:Rouveix,Elisabeth;Charleville:Galempoix,Jean-Marc;Dijon:Piroth,Lionel;Lyon:Cotte,Laurent;Metz-Thionville:Truchetet,François;Pouaha,Jean;Muller,Philippe;Paris–Bichat:Bouvet,Elisabeth;Pellissier,Gérard;Paris–PitiéSalpêtrière:Simon,Anne;Paris–SaintAntoine:Valin,Nadia;Paris–Tenon:Lebrette,Marie-Gisèle;Reims:Bani-Sadr,Firouzé;Rennes:Souala,MohamedFaouzi;Strasbourg:Rey,David;Batard,Marie-Laure;Fischer,Patricia;Gantner,Pierre;Tourcoing:Ajana,Faiza.

NS NS NS NS NS