Approach for the Newly - The American Conference for the ... · • Didanosine(Videx) •...

JasonE.Farley,PhD,MPH,ANP-BC,FAAN,AACRNAssociateProfessor&NP,JohnsHopkinsUniversitySchoolofNursing&Medicine

Director,AETCAdult-GerontologyPrimaryCareHIVCertificateProgramClinicalCoreCo-Director,JohnsHopkinsCenterforAIDSResearch

President,AssociationofNursesinAIDSCare

ApproachfortheNewlyDiagnosedHIVPositivePatient

ObjectivesDetailstrategiesforTESTandTREATapproaches

Discussthefirst-lineARTregimensfortreatmentnaïveindividuals.

ReviewclinicalconsiderationswhenselectinganinitialARTregimen

Describefollow-upmonitoringofpatientsnewlystartedonART

TheNewlyDiagnosedPatient• Deliveringtheresultsvs.postresultvisit

• Connectclientstoneededservices:– HIVtreatmentsupport

• Peer,pharmacist,adherencegroups– Partnerservices– Otherrelevantservices(e.g.drugtreatment)

• Addresspatientfeelingsand/orconcerns

• Totreatornottotreat?

TheMovementtoTestandTreathttps://hptn.org/research/studies/hptn065

Maryland Prevention and Health Promotion Administration

April 2, 201555

Improvements in the Continuum of Care

80

54

37

2416

100

82

57

3528

22

84

61

4739

30

86

70

50

41

32

HIV Infected HIV Diagnosed Linked to HIVCare

Retained in HIVCare

On ART Suppressed VL0

10

20

30

40

50

60

70

80

90

100

Engagement in HIV Care

Estimated percentage of HIV infected adults/adolescents engaged in selected stages of the continuum of care, Maryland 2010-2013

2010201120122013

FactorWhen to Treat Recommendations

2007 2009 2010 2012 2013/14

AIDS Treat Treat Treat Treat Treat

CD4 count(cells/mm3)

• Treat <350• Risks/benefit

s if >350

• Treat <350• Rec

350 -500• >500 optional

• Treat <350• Rec 350 - 500• >500 optional

(panel split)

• Rec for all <350 (AI)

• 350 -500 (AII)• >500 (BIII)

Everyone (regardless of

CD4)Test & Treat

Viral load (copies/mL)

No specific viral load





Other factors

• Pregnant women

• HBV co-infected• HIVAN

• Pregnant women


• Pregnant women


• Pregnant women


• Treat to prevent infection

EvolutionofDHHSGuidelines

BenefitsofearlyART

• Preventionofcomplications– Includingnon-communicablediseases

• Preventsexualtransmission

• Preventmothertochildtransmission

• Preserveimmunefunction

DrugClassAbbreviations:

EI:EntryInhibitors

FI:FusionInhibitors

INSTI:IntegraseInhibitors

NNRTI:Non-nucleosidereversetranscriptaseinhibitors

NRTI:Nucleosidereversetranscriptaseinhibitors

PI:Proteaseinhibitor

PE:Pharmacologicenhancer

FCD:FixedDoseCombination

Note:drugsingrayarenolongerrecommendedforuse

CurrentARVMedicationswithGeneric(Trade)Names:

• NRTI• Abacavir (Ziagen)• Didanosine (Videx)• Emtricitabine (Emtriva)• Lamivudine(Epivir)• Stavudine (Zerit)• Tenofovir (Viread)/TAF• Zidovudine(Retrovir)•• NNRTI• Delavirdine (Rescriptor)• Efavirenz (Sustiva)• Etravirine (Intelence)• Nevirapine (Viramune)• Rilpivirine (Edurant)

• PI• Atazanavir (Reyataz)• Darunavir (Prezista)• Fosamprenavir (Lexiva)• Indinavir (Crixivan)• Lopinavir/r(Kaletra)• Nelfinavir (Viracept)• Ritonavir(Norvir)• Saquinavir (Invirase)• Tipranavir (Aptivus)

• Integrase Inhibitor(II)• Dolutegravir (Tivicay)• Elvitegravir*(Stribild)• Raltegravir (Isentress)

• FusionInhibitor• Enfuvirtide (Fuzeon)

• CCR5Antagonist• Maraviroc (Selzentry)

Deeks,etal,2015;NatureReviews

ChoosingtheRegimen

• Reviewbaselinelabsincludinggenotype• Reviewco-morbiddiseasesincludingage• Assessadherencepotential

• Synthesizethisinformationforregimenselection

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. US Dept of Health and Human Services; 2016

Baselinelaboratoryevaluations• CD4T-cellcount(CD4

count);• PlasmaHIVRNA(viral

load)• Completebloodcount,

chemistryprofile,transaminaselevels,BUN,andcreatinine,urinalysis;

• Serologies forhepatitisA,B,andCviruses

• HLA-B5701– Abacavir regimens– only

needonce

• Fastingbloodglucoseandserumlipids

• Genotypicresistancetestingatentryintocare,regardlessofwhetherARTwillbeinitiatedimmediately.– ForpatientswhohaveHIV

RNAlevels<500to1,000copies/mL,viralamplificationforresistancetestingmaynotalwaysbesuccessful


http://

aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/6/drug-resistance-testing

Resistance Testing Decision Tree

Trofile Assay(MVC)

Limitedtreatmentoptions

Complexresistantpatterns

Non-responseNon-adherence

Baseline(Pre-ART)

Genotype Phenotype

ResistanceOptions

INSTI(Optional)

Choosing the Right ART Regimen for Your Patient: A Patient Centered Approach

Joint decision

Side Effects

Drug Drug Interactions

Costs / Copays

Adherence / Dosing

Preference

Co-Morbidity

Resistance

08

01

02

03

04

05

06

07

TreatingHIV….the3-2-1principle

Atleast3differentDRUGS

Atleast2differentCLASSES

TryforoncedailyDOSING


TDF/FTC § Once-dailyandincombinationdosing§ High virologicefficacy§ ActiveagainstHBV§ Potentialforrenalandbonetoxicity

TAF/FTC § Once-daily andincombination§ Highvirologic efficacy§ NOapprovalforHBVco-infection§ Improvedrenalandbonetoxicity profile

ABC/3TC § Once-dailydosing§ Must beHLA-B*5701negative§ Possible riskofcardiovascularevents**§ PossibleinferiorefficacyifbaselineHIVRNA

>100,000copies/mL


Beginwiththe“Nuc”backbone

• Welltolerated• MustbeHLA-B5701

negative• Highbarrierto

resistance

Triumeq• Welltolerated• Takewithmeals• AvoidifVL>

100,000copies/mL• PHsensitive

Odefsy /Complera• Welltolerated• Drug-drug

interactions(CYP450)• Cobi– incr Cr;avoid

ifCrCl<70

Stribild• Welltolerated• MustbeHLA-B5701

negative(ABC)• Donotuseifknown

INSTIresistance

Genvoya

DTV/ABC/3TC

RPV/TAF/FTCor

RPV/TDF/FTC

ELV/Cobi/TDF/FTC

ELV/TAF/FTC/COBI

1st line ART regimen (single tablet)


• 3pillsoncedaily• Veryforgivingregimen

(Greatfor?adherence)• Generallywelltolerated• Drug-druginteractions

Darunavir/cobi+Descovy

• 3pillsoncedaily• Hyperbilirubinemia• PHsensitive• Drug-druginteractions

Atazanavir/rtv+Descovy

• 2tabletsoncedaily• Welltolerated

Dolutegravir +Descovy

DRV/COBI+TAF/FTC

ATV/COBI+TAF/FTC

DTV+TAF/FTC

1st line ART regimen (2 tabs / once daily)


Cobicistat co-formulation:• Darunavir/cobi

• Prezcobix

BENEFITS:• Lowerpillburden

NEGATIVES:• ArtificialriseinCreat

Considerations

§ Patientsshouldbewillingandableto:§ commit totreatment§ understandbenefits,risks§ understand importanceofadherence

§ PatientsorprovidersmayelecttodeferART§ limitedreasonwhythisshouldoccur


Factors Associated with Adherence Challenges

• Regimen complexity and pill burden

• Low literacy/numeracy• Younger age

– Some challenges of older age (eg, polypharmacy, vision loss, cognitive impairment)

• Nondisclosure of HIV status

• Stigma

§ Psychosocial stressors§ Active drug use or

alcoholism § Mental illness § Cognitive impairment§ Lack of patient education§ Medication adverse effects§ Treatment fatigue§ Cost and insurance

coverage issues

Factors Associated with Adherence Success

• Regimen simplicity, once-daily dosing

• Low pill burden• Good tolerability• Older age• Multidisciplinary care (eg, with

case managers, social workers, pharmacists, psychiatric care providers)

• Directly observed therapy

§ Trusting patient-provider relationship

§ Use of motivational strategies

Monitoringviralload• MoreimportantthanCD4countforongoingmonitoring

• CompletebaselineviralloadtestingbeforeinitiationofART

• Checkviralload– Within4weeksafterstartorchangeofART– Every3-4monthsforstable,butnewerpatients– Every6-12monthsforlongtermadherentpatients

CaseStudy#1

• PhysicalExam:lymphadenopathy• BMI:26kg/m2

• BaselineDiagnosticData:– CD4+:385cells/µL(20%)– HIVRNA:76,000copies/mL– HIVGenotype:noresistance– eGFR:110ml/min/1.732

• (serumCr:0.6mg/dL)– HLA*B5701:negative

19 y/o femaleNewly diagnosed

No primary partner

On OCP

No other PMH

01

TheDecisiononARTRegimen

A. 2nucleosides+elvitegravir /cobicistatB. 2nucleosides+rilpivirineC. 2nucleosides+dolutegravirD. 2nucleosides+darunavir /cobicistat

Case#1- continued

• Startedonfixed-dosecombinationoftenofovir alefenomide/emtricitabine/elvitegravir/cobicistat (Genvoya)

• 4weeksafterstartingtherapythepatientreturnsforfollowup.– Doingwellwithnoacutecomplaints

RepeatLabs:Week4

LaboratoryTest Result

CD4+ T-CellCount(%)

420cells/m3

(21%)HIVRNA <20copies/mLCreatinine 0.9 mg/dLeGFR 69mL/min/1.73m2

**Frombaseline110mL/min/1.73m2

Whatisthebestnextstep?

A. Continuetreatment;monitorrenalfunction

B. StopARTduetorenaltoxicity

C. Switchtoraltegravirwithtenofovir/emtricitabine

D. Switchtoabacavir/lamivudinewithdolutegravir

Figure5ChangeofserumcreatinineconcentrationfrombaselineBarsareIQR.Dataareforthesafetypopulation.

Saxetal.TheLancet,Volume379,Issue9835,2012,2439- 2448DeJesus,etal,Lancet.Vol379,no.9835,p2429–2438,30June2012

EffectofElvitegravir/cobicistat onSerumCreatinine

Case#1- Follow-up

• Patientremainsontenofovir/emtricitabine/elvitegravir/cobicistat

• eGFRremainsstable>60ml/min/1.732

• HIVremainsfullysuppressed

CaseStudy#2– 42yearoldmale• PhysicalExam:Unremarkable

– HTN,DMwellcontrolledwithnotargetorgandamage– LDLcholesterol=115mg/dL

• BaselineDiagnosticData:– CD4+:540cells/µL(20%)– HIVRNA:123,000copies/mL– HIVGenotype:noresistance– eGFR:89ml/min/1.732

• (serumCr:1.1mg/dL)– HLA*B5701:negative

– NewHCVDiagnosis• NormalALT,AST• HCRRNA1.3millioncopies/mL

0242 y/o male

Newly diagnosed

DM, HTN

Hyperlipidemia

A. 2nucleosides+elvitegravir /cobicistatB. 2nucleosides+rilpivirineC. 2nucleosides+dolutegravirD. 2nucleosides+darunavir /cobicistat

TheDecisiononARTRegimen#2

Peripheralnervoussystem– Neuropathy,myopathy

Metabolic• Glucosedisorders

– Insulinresistance– Impairedglucosetolerance– Hyperglycemia/diabetes

• Lipidelevations– ¯ HDL, triglycerides– cholesterol

• Hyperlactatemia– Lacticacidosis

Morphologic• Fataccumulation(lipodystrophy)

– Abdominalobesity– Buffalohump– Lipomatosis– Breastenlargement– Gynecomastia

• Fatlossandredistribution(lipoatrophy)

Renal• TDFtoxicityCardiovascular• Myocardialinfarction

Preventing&MonitorforLong-TermComplicationsAssociatedwithART

Beonthelookout:Drug-DrugInteractionsareCOMMON

• Ritonavir (usedwithPI)– CYP450Inhibitor!

• fluticasone• warfarin• rifampin• sildenafil (Viagra)

– Newformulationshouldbetakenwithfood

• EFVdecreasesMethadonebyupto67%

• Atazanavir– MusthaveacidicPH

• AvoidPPIorH2Blockers

• SeveralHIVagentsmusthavedosingchangestobeusedtogether

Potentiallifethreateninginteractions

http://www.hiv-druginteractions.org(UK)https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/32/drug-interactions

3A4

2C19 2D6 2C9

1A2 2E1 2A6 2B6 2C8

Induced by: RTV, NFV, LPV, EFV, NVP, TPV,

ETRInhibited by: RTV, NFV, IDV,

APV, SQV, ATV, DRV, DLV, COBI

Induced by: RTV, NFV, EVG

Inhibited by: DLV, ATV, ETR

Induced by: EFV,NVP

Inhibited by: RTV, COBI

Induced by: RTV, NFV

Inhibited by: EFV, DLV, ETR

Induced by: RTV,NFV?

DrugInteractions:EffectofARVsonDrugMetabolism

Fichtenbaum CJ. Clin Pharmacokinet. 2002:41:1195-1211; Package inserts.

Inhibited by:ATV

JohnsHopkinsAETC/CFAR

• FollowusonFacebook– https://www.facebook.com/JohnsHopkinsAETC– https://www.facebook.com/JHUCFAR– https://www.facebook.com/Prep4tomorrow

• Followontwitter– @HopkinsCFAR– @jfarleyfarleyJHU– @ANACNurses

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