Post on 13-Jul-2020
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
1
2
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Viremiadetectable:pacientenaïve
Viremiadetectablehttp://gesida-seimc.org/wp-content/uploads/2017/02/gesida-guiasclinicas-2017-TAR.pdf.
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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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Viremiadetectable:pacientenaïve
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:pacientenaïve
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:pacientenaïve
Viremiadetectablehttp://gesida-seimc.org/wp-content/uploads/2017/02/gesida-guiasclinicas-2017-TAR.pdf.
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Viremiadetectable:pacientenaïve
Viremiadetectable
Clinically Relevant Transmitted Drug Resistance to First LineAntiretroviralDrugs
Source:Monge S,etal.PLoS ONE2014;9:e90710–7.
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Viremiadetectable:pacientenaïve
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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Viremiadetectable:pacientenaïve
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:pacientenaïve
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:pacientenaïve
Viremiadetectable
Overview ofclinical guidelines andfirst lineARToptions
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Viremiadetectable:pacientenaïve
Viremiadetectable
INSTIs:Drug Characteristics
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Viremiadetectable:pacientenaïve
Viremiadetectable
INSTIs:Patient factors to consider
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Viremiadetectable:pacientenaïve
Viremiadetectable
NRTIbackbone:Drug Characteristics
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Viremiadetectable:pacientenaïve
Viremiadetectable
NNRTIs:Drug Characteristics
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Viremiadetectable:pacientenaïve
Viremiadetectable
NNRTIs:Patient Factors to Consider
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Viremiadetectable:pacientenaïve
Viremiadetectable
PIs:Drug Characteristics
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Viremiadetectable:pacientenaïve
Viremiadetectable
Impact ofMedicalComorbidities on treatment selection
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Viremiadetectable:pacientenaïve
Viremiadetectable
Impact ofMedicalComorbidities on treatment selection
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Viremiadetectable:pacientenaïve
Viremiadetectable
Impact ofMedicalComorbidities on treatment selection
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Viremiadetectable:pacientenaïve
Viremiadetectable
Individualpatient characteristi to consider when choosing treatment
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Viremiadetectable:pacienterecibiendotratamiento
Viremiadetectable
Blip
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Viremiadetectable:pacienterecibiendotratamiento
Viremiadetectable
Virologic failure
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Viremiadetectable:pacienterecibiendotratamiento
Viremiadetectable
CausesofTreatmentFailure
Pooradherence
Insufficientdruglevel
Viralreplicationinthepresenceofdrug
Resistantvirus
Social/personalissuesRegimenissues
Toxicities
Suboptimalpotency
Wrongdose
Hostgenetics
Poorabsorption
RapidclearancePooractivation
Druginteractions
Virologicfailure
TransmittedorAcquired
DHHSGuidelines.
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Viremiadetectable:pacienterecibiendotratamiento
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:pacienterecibiendotratamiento
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:pacienterecibiendotratamiento
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:pacienterecibiendotratamiento
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:pacienterecibiendotratamiento
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:pacienterecibiendotratamiento
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:pacientenaïve
Viremiadetectable
When to start?2020challenge
Source: