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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
No specific viral load
No specific viral load
No specific viral load
No specific viral load
Other factors
• Pregnant women
• HBV co-infected• HIVAN
• Pregnant women
• HBV co-infected• HIVAN
• Pregnant women
• HBV co-infected• HIVAN
• Pregnant women
• HBV co-infected• HIVAN
• 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
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
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
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
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
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
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)
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
• 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)
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; 2015
Cobicistat co-formulation:• Darunavir/cobi
• Prezcobix
BENEFITS:• Lowerpillburden
NEGATIVES:• ArtificialriseinCreat
Considerations
§ Patientsshouldbewillingandableto:§ commit totreatment§ understandbenefits,risks§ understand importanceofadherence
§ PatientsorprovidersmayelecttodeferART§ limitedreasonwhythisshouldoccur
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
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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