Mi paciente tiene una viremia detectable …… y ahora qué...

Mipacientetieneunaviremiadetectable……yahoraquéhago?”

Dr.Jose RArribas

@jrarribas

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GESIDAGuidelines

Viremiadetectablehttp://gesida-seimc.org/wp-content/uploads/2017/02/gesida-guiasclinicas-2017-TAR.pdf.

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EACSGuidelines

Viremiadetectablehttp://www.eacsociety.org/files/guidelines_8.2-english.pdf.

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Viremiadetectable

Viremiadetectable

Enunpacientenaïve

Enunpacienterecibiendotratamiento

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Viremiadetectable:pacientenaïve


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STARTSTUDYDESIGN

ViremiadetectableSource:LundgrenetalNEJM2015

HIV-infected individuals who are ART-naïve with CD4+ count > 500 cells/mm3

Immediate ART Group

Initiate ART immediately following randomization

N=2,326

Deferred ART Group

Defer ART until CD4+ count drops to <350 cells/mm3 or AIDS develops

N=2,359

Primary endpoint:• Serious AIDS• Serious non-AIDS conditions

CVD (stroke, MI, revascularization), ESRD, decompensated liver disease, non-AIDS cancer• All-cause death

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ViremiadetectableSource:LundgrenetalNEJM2015

ImmediateART

DeferredART

No.withEvent

42 96

Rate/100PY 0.60 1.38

HR(Imm/Def) 0.4395%CI: 0.30- 0.62

p<0.001

ARR/100PY(Def-Imm)

0.7895%CI: 0.46- 1.12

NNT 128

4.1

1.8

START:Primary Endpoint

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Viremiadetectable

Source: 1.AdaptedfromKarim SSandKarim QA.Lancet2011;378:e23–25;2.WellerSandDavisK.CochraneDatabaseSyst Rev2002:CD003255;3.SmithDKetal.JAIDS2015;68:337–344;4.MartinMetal.AIDS2015;29:819‒24;5.vanDamme Letal.NEJM2012;367:411–422;6.Marrazzo JMetal.CROI2013.Atlanta,GA.#26LB

FEM-PrEPinwomen,5VOICE(PrEP,PrEPvaginalgel)inwomen6,

0 10 20 30 40 50 60 70 80 90 100

Efficacy(%)

Study ReducLoninHIVtransmission

Notsignificant*

*FEM-PrEP:HR0.94VOICE:OralPrEP:HR[1.49,1.04],PrEPvaginalgel:HR0.85HIVvaccine:31%reduc@onintransmission

Condomsinheterosexuals2HPTN052(ARVtreatmentasprevenLon)1 96%

80%PartnersPrEPindiscordantcouples1

73%

CondomsinUSMSM3 70%

BangkokPrEPinIDU4

49%

TDF2inmen&women1 63%Medicalmalecircumcision1 54%

CAPRISA004(1%PrEPvaginalgel)inwomen1 39%iPrExinMSM1

44%

HIVvaccine(RV144)1 31%

Relativeefficacyandpreventionstrategies

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Viremiadetectable

Clinically Relevant Transmitted Drug Resistance to First LineAntiretroviralDrugs

Source:Monge S,etal.PLoS ONE2014;9:e90710–7.

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ViremiadetectableSource:CORIS– Cohorte delaReddeInvestigación enSIDA

10.9%(10-11.8)NNRTIs 2.1%NRTIs 9%,;IPs0.8%

Prevalencia(95%CI)

Resistencia Intermedia Total

ITIANs Tenofovir 1.5(1.2-2.0) 9(0.2) 62(1.3) 71

Emtricitabina 0.9(0.5-1.1) 33(0.7) 11(0.2) 44

Lamivudina 0.9(0.5-1.1) 33(0.7) 11(0.2) 44

Abacavir 2.1(1.6-2.6) 12(0.2) 87(1.8) 99ITINANs Efavirenz 4.6(3.6-5.0) 156(3.3) 62(1.3) 218

Nevirapina 5.1(4.2-5.5) 188(3.9) 55(1.1) 243

Rilpivirina 5.3(4.5-5.7) 20(0.4) 231(4.8) 250IPs Lopinavir 0.5(0.2-0.8) 4(0.1) 19(0.4) 23

Atazanavir 0.8 (0.4-1.1) 4(0.1) 33(0.7) 37

Darunavir 0.2(0.04-0.3) 1(0.02) 9(0.2) 10

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Viremiadetectablehttp://www.gesida-seimc.org/contenidos/guiasclinicas

Preferred ARTinGESIDAGuidelines

• Applicabletothemajorityofpatients• InRCTsuperiorvscontrol• InRCTnon-inferiorbuthaveasuperiortolerance,toxicityorinteraction

profile

• 88-90%with<50copies/mLatweek48byFDAsnapshot• <1-2%virologic failures• 1-2%discontinuationsduetoAE

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Viremiadetectable

Preferred ARTinGESIDAGuidelines

2017Preferred

http://www.gesida-seimc.org/contenidos/guiasclinicas/

ABC/3TC-DTGTDF(TAF)/FTC-DTGTDF(TAF)/FTC-RALTAF/FTC/EVG/c

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Viremiadetectable

Overview ofclinical guidelines andfirst lineARToptions

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Viremiadetectable

INSTIs:Drug Characteristics

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Viremiadetectable

INSTIs:Patient factors to consider

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Viremiadetectable

NRTIbackbone:Drug Characteristics

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Viremiadetectable

NNRTIs:Drug Characteristics

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Viremiadetectable

NNRTIs:Patient Factors to Consider

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Viremiadetectable

PIs:Drug Characteristics

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Viremiadetectable

Impact ofMedicalComorbidities on treatment selection

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Viremiadetectable


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Viremiadetectable


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Viremiadetectable

Individualpatient characteristi to consider when choosing treatment

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Viremiadetectable:pacienterecibiendotratamiento

Viremiadetectable

Blip

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Viremiadetectable

Virologic failure

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Viremiadetectable

CausesofTreatmentFailure

Pooradherence

Insufficientdruglevel

Viralreplicationinthepresenceofdrug

Resistantvirus

Social/personalissuesRegimenissues

Toxicities

Suboptimalpotency

Wrongdose

Hostgenetics

Poorabsorption

RapidclearancePooractivation

Druginteractions

Virologicfailure

TransmittedorAcquired

DHHSGuidelines.

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Viremiadetectable

EARNEST:Second-lineLPV/RTV± RALor2-3NRTIsinPI-NaivePts

Paton NI,etal.NEngl JMed.2014;371:234-247.

• Randomized,open-label,multicenterphaseIIItrialinsub-SaharanAfrica

LPV/RTV+RAL(n=433)

LPV/RTV+2-3NRTIs*(n=426)

HIV-infectedpts>12yrsofage

withconfirmedVFonNNRTI+2NRTIsandnopriorPIs

(N=1277)

Wk96

LPV/RTV400/100mgandRAL400mgdosedBID.*NeworrecycledNRTIschosenWITHOUTgenotypebyclinician.

Wk12

LPV/RTVMonotherapy(n=418)

LPV/RTV+RAL(n=418)

Stratifiedbystudycenter,CD4+cellcount(<200vs≥

200cells/mm3)

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Viremiadetectable

EARNEST:BoostedPI+RALComparabletoBoostedPI+NRTIs

Source:1.Paton NI,etal.NEngl JMed.2014;371:234-247.2.Paton,NI,etal.ACHA2015.3.AminJ,etal.PLoS One.2015;10:e0118228.4.LaRosaAM,etal.CROI2016.Abstract30.5.LaRosaAM,etal.LancetHIV.2016;3:e247-e258.

• SECOND-LINE[3] andACTG5273[4,5] showedsimilarresults

LPV/RTV+RAL(n=433)LPV/RTV+2/3NRTIs(n=426)LPV/RTVmonotherapy(n=418)

100

80

60

40

20

0

Pts(%)

HIV-1RNA<50copies/mL,Wk96[1]

7473

44

P <.001

HIV-1RNA<400copies/mLThroughWk144[2]

0

20

40

60

80

100

LPV/RTV+NRTI(NumberofActiveNRTIs)

Pts(%)

88

0 LPV/RTV +RAL

77 8185

61

1 2-3

LPV/RTV

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Viremiadetectable

DHHS:ManagementofFirst-lineFailure

*If RAL or EVG resistance detected, DTG + boosted PI can be used if DTG susceptible.

FailingRegimen(+NRTIs)§ BoostedPI: Enforceadherence

Modifyforconvenienceortoxicity§ NNRTI: BoostedPI+NRTIs

BoostedPI+INSTI§ INSTI: BoostedPI+NRTIs

BoostedPI+activeINSTI*

*If RAL or EVG resistance detected, DTG + boosted PI can be used if DTG susceptible.

DHHSGuidelines.

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Viremiadetectable

DHHS:ManagementofARTFailureSecond-lineARVFailure

DHHSGuidelines.

• Goal:fullysuppressiveARVregimen• IfsusceptibletoboostedPI,regimencanbe

similartothoseforfirst-linefailure• IfnotsusceptibletoboostedPI,newregimen

shouldhaveaminimumof2(preferably3)fullyactivedrugsifpossible

– Susceptibilitytodrugpredictedfrompttreatmenthistory,priorandcurrentresistanceandtropismtesting,MoAofnoveldrugclass

• Notrecommendedtoaddsingleagenttofailingregimenduetoriskofdevelopingresistancetoentireregimen

BoostedPI+NRTIsBoostedPI+activeINSTI

2andpreferably3fullyactivedrugs

Yes No

PISusceptible

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Viremiadetectable

EmergingInvestigationalAgentsforPts WithMDRHIV

1. Lalezari JP,etal.Lancet HIV.2015;2:e427-437.2. Granados-ReyesER,etal.HIVGlasgow2016.Abstract O335A.3. ClinicalTrials.gov.NCT02362503.4. LewisS,etal.CROI2017.Abstract 449LB.5. Lin H-H,etal.CROI2017.Abstract 438.6. Lalezari J,etal.CROI2017.Abstract 437

InvestigationalAgent Phase MoA

Fostemsavir[1-3] III Prodrug;whenmetabolizedbindsgp120topreventCD4+cellattachment,entry

Ibalizumab[4,5] III Humanizedanti-CD4receptormAbPRO 140[6] IIb/III Humanizedanti-CCR5mAb

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Viremiadetectable

Rebote debajo nivel

Fecha ART Carga viral Mutaciones

15/05/16 E/C/F/TAF <50

12/12/16 E/C/F/TAF 46115/12/16 E/C/F/TAF 45402/02/17 DTG-F/TAF 445 V90I,V106I,L10I13/03/17 DTG-F/TAF 44316/03/17 DTG-F/TAF <50(LCR)27/03/17 DTG-F/TAF 110

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Viremiadetectable

When to start?2020challenge

Source:

Mi paciente tiene una viremia detectable …… y ahora qué...

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