An Antiretroviral Therapy Review Sarah Pérez PharmD PhC BCACP AAHIVP Disclosure The speaker has no actual or potential conflicts of interest in relation to this presentation Objectives Pharmacists ID: 775352
Download Presentation The PPT/PDF document " The ART of HIV Management: " is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
The ART of HIV Management: An Antiretroviral Therapy Review
Sarah Pérez, PharmD, PhC, BCACP, AAHIVP
Slide2Disclosure
The speaker has no actual or potential conflicts of interest in relation to this presentation.
Slide3Objectives
Pharmacists
Identify recommended initial antiretroviral therapy (ART) regimens for most treatment naïve people with HIV
Evaluate common drug-drug interactions between ART and other medications
Describe the role pharmacist in various setting can play in HIV patient care
Pharmacy Technicians
Identify commonly prescribed antiretroviral therapy (ART) regimens
Identify medications that contain tenofovir disoproxil fumarate vs tenofovir alafenamide
Describe the role pharmacy technicians can play in HIV patient care
Slide4Slide5Slide6HIV in United States
At the end of 2016, an estimated 1.1 million people aged 13 and older had HIV infection Approximately 38,700 Americans became newly infected in 201652% of these new infections were in the South1 in 7 individuals living with HIV are unaware of their status
1. https://www.cdc.gov/hiv/statistics/overview/index.html,
2. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics
Slide7HIV in New Mexico—2016
3,442 people were living with HIV infection134 new HIV diagnosis is adults and adolescents54 people were newly classified as having stage-3 HIV infection (AIDS)34 people had HIV infection progress to stage-3
https://nmhealth.org/data/view/infectious/2139/
Slide8HIV Care Continuum, 2015
https://www.cdc.gov/hiv/pdf/library/factsheets/cdc-hiv-care-continuum.pdf
Retained
In Care
Percent of all people living with HIV in US
Slide9HIV Transmission Risk
Potentially infectiousBloodBreast milkTissueSemenVaginal secretionsVisibly bloody fluidsOther bodily fluids
NOT infectiousUrineSalivaSweatTearsNasal secretionsSputumVomitusStool
https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/how-is-hiv-transmitted
Slide10Estimated Per-Act Probability of Acquiring HIV from an Infected Source
Type of ExposureRisk per 10,000 ExposuresParenteralBlood Transfusion9,250Needle-Sharing During Injection Drug Use63Percutaneous (Needle-Stick)23SexualReceptive Anal Intercourse138Insertive Anal Intercourse11Receptive Penile-Vaginal Intercourse8Insertive Penile-Vaginal Intercourse4Receptive Oral IntercourseLowInsertive Oral IntercourseLow
https://www.cdc.gov/hiv/risk/estimates/riskbehaviors.html
Slide11Treatment as Prevention
People with HIV who maintain an undetectable viral load for at least 6 months do not transmit HIV through condomless sex.
1. https://www.preventionaccess.org/consensus
2. https://www.cdc.gov/hiv/risk/art/index.html
Slide12Facilitators and Barriers to Treatment
Pill burden
Adverse effectsBarrier to resistanceCost/coverageDrug interactions
Social issuesFinancesHousingAccess to foodTransportationSocial supportComorbiditiesPsychosocial issuesStigma
InsuranceAccess to servicesFormulariesPrior authorizationsRestrictions to specialty pharmaciesStigma/discriminationCultural competency
Slide13Facilitators and Barriers to Treatment
ART Selection
Slide14Antiretroviral Drug Targets
Fusion inhibitor
NRTIs, NNRTIs
Integrase Inhibitors
Protease Inhibitors
Co-receptor antagonist
https://www.nature.com/articles/nrmicro3351/figures/1
NRTIs
: Nucleoside Reverse Transcriptase Inhibitors
NNRTIs
: Non-nucleoside Reverse Transcriptase Inhibitors
Slide15Antiretroviral Regimen Selection
2 to 3 drug regimen from at least 2 different drug classesFactors to considered for ART selectionPretreatment HIV VL and CD4 countHIV genotype drug resistance testingART historyHLA-B*5701 statusPatient preferenceAnticipated adherence to regimen
Comorbidities
Drug interactions
Adverse effects
Pill burden
Cost/ insurance coverage
Slide16Treatment Goals
Maximally and durably suppress plasma HIV RNAUndetectable HIV viral loadRestore and preserve immunologic functionImprove and maintain high stable CD4 countReduce HIV-associated morbidity and prolong duration & quality of survivalPrevent HIV transmission
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/9/treatment-goals
Slide17Predictors of Virologic Success
Low baseline viremiaHigh potency of the ART regimenTolerability of the regimenConvenience of the regimenExcellent adherence to the regimen
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/9/treatment-goals
Slide18Recommended Initial Regimen for Most People with HIV
Bictegravir/emtricitabine/TAFDolutegravir/lamivudine/abacavir*Dolutegravir + emtricitabine/TDF OR emtricitabine/TAFRaltegravir + emtricitabine/TDF OR emtricitabine/TAF
INSTI= Integrase Strand Transfer InhibitorNRTI=Nucleoside Reverse Transcriptase InhibitorTDF=tenofovir disoproxil fumarateTAF=tenofovir alafenamide*Only for patients HLA-B*5701 negative
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/11/what-to-start
1 INSTI + 2 NRTIs
Slide19Tenofovir Disoproxil Fumarate VS Tenofovir Alafenamide
1. Lee W et. Antimicr Agents Chemo 2005;49(5):1898-1906. 2. Birkus G et al. Antimicr Agents Chemo 2007;51(2):543-550. 3. Babusis D, et al. Mol Pharm 2013;10(2):459-66. 4. Ruane P, et al. J Acquir Immune Defic Syndr 2013; 63:449-5. 5. Sax P, et al. JAIDS 2014. 2014;67(1):52-8. 6. Sax P, et al. Lancet 2015;385:2606-15.
HIV
TARGET CELL
AMIDATE
ESTER
DIANION
GI TRACT
Tenofovir alafenamide
(TAF)
Tenofovir disoproxil
fumarate
(TDF)
Tenofovir
(TFV)
Parent
Nucleotide
T
1/2
= 90 min
†
T
1/2
= 0.4 min
†
PLASMA
TAF
25 mg
TDF 300 mg
TFV
TFV
TFV
TFV
HIV
Slide20Bictegravir/emtricitabine/TAF (Biktarvy®)Dolutegravir/lamivudine/abacavir (Triumeq®) Dolutegravir (Tivicay®) + emtricitabine/TDF (Truvada®) OR emtricitabine/TAF (Descovy ®)Raltegravir (Isentress®) 400mg BID + Truvada® OR Descovy®Raltegravir (Isentress HD ®) 1200mg daily + Truvada® OR Descovy®
OR
+
+
+
Recommended Initial ART Regimens
OR
OR
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/11/what-to-start
Slide21Slide22Other Common ART (NNRTI-Based)
Rilpivirine (Edurant®)Must be taken with a full mealDo not initiate in individuals with CD4 count <200 or HIV VL > 100,000Rilpivirine/emtricitabine/TDF (Complera®)Rilpivirine/emtricitabine/TAF (Odefsey®)
Slide23Pharmacokinetic Enhancers (Boosters)
Must be administered with most PIs and INSTI elvitegravir
Allow higher drug exposure, lower pill burden, less frequent dosing
Ritonavir and cobicistat work by inhibiting CYP3A4
Cobicistat coformulated with newer regimens requiring a booster
Cobicistat only approved from once a day PIs
If PI is BID then ritonavir is administered BID
Slide24Other Common ART (PI-Based)
Darunavir (Prezista®)Should be taken with food600mg BID dosing in pregnancy or treatment experienced with darunavir resistanceDarunavir (Prezista®) + ritonavir (Norvir®) + Truvada® OR Descovy®Darunavir/cobicistat (Prezcobix ®) + Truvada® OR Descovy®Darunavir/cobicistat/emtricitabine/TAF (Symtuza®)
OR
OR
+
+
+
Slide25Other Common ART (INSTI-Based)
Elvitegravir Should be taken with foodAlways administered with cobicistatElvitegravir/cobicistat/emtricitabine/TDF (Stribild®)Elvitegravir/cobicistat/emtricitabine/TAF (Genvoya®)
Slide26Other Common ART (2 drug NNRTI/INSTI)
Rilpivirine/dolutegravir (Juluca®) Indication: individual with HIV virologically suppressed on a stable ART regimen for ≥ 6 months with no history of treatment failure and no known resistance to the individual componentsMust be taken with a full meal
Juluca [package insert]. Research Triangle Park, NC:
Viiv
Healthcare; 2017
Slide27Management of Treatment-Experienced Patients
Based on ART history and resistance patterns
Generally at least 2 to 3 active drugs if possible
Often 2 NRTIs + another class
May be NRTI sparing
May require dose adjustment of ART agents
Slide28Facilitators and Barriers to Treatment
Drug Interactions
Slide29Complexity of ART
Increased number of antiretroviral agents and combination productsPatients may be unable to recall complex regimensLack of medication knowledge by prescribersNon-HIV/ID providers are not well familiar with appropriate ARTHigh adherence rates required for virologic suppressionDrug resistance can drastically limit future ART options
Eginger KH, et al. Ann Pharmacother 2013;47:953-60.
Slide30Medication Errors in HIV-Infected Hospitalized Patients
Occur in ~30% to 40% of patientsCommon Errors:Improper antiretroviral regimensInappropriate dosingMissing agentsDrug interactionsOmission of opportunistic infection prophylaxis
Eginger KH, et al. Ann Pharmacother 2013:47:953-60Chiampas TD, et al. Pharm Pract 2015; 13:512
Slide31Drug-Drug Interactions
Pharmacokinetic (PK) drug interactions between ART and concomitant medications can caused increased or decreased drug exposures to either drugPK interactions can occur during absorption, metabolism, or elimination of ARTEffects on ART drug levels can cause increased toxicities or decreased therapeutic responseART treatment failure is a possible result of drug interactions
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/367/overview
Slide32Resources for ART Drug Interactions
Make sure references are updated on a regular basis and using most updated version
Panel on Antiretroviral Guidelines for Adults and Adolescents (DHHS Guidelines)
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/367/overview
University of Liverpool HIV Drug Interaction Checker
https://www.hiv-druginteractions.org/
Other drug reference databases (Lexicomp, Clinical Pharmacology, Micromedex, etc.)
Slide33NRTI Drug Interactions
Minimal number of clinically significant drug interactionsDo NOT coadminister emtricitabine and lamivudineDo NOT coadminister TDF and TAFCaution with other nephrotoxic drugs and TDFAvoid major CYP3A4 inducers with TAFCarbamazepineOxcarbazepinePhenytoinPhenobarbital
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/286/nrti-drug-interactions
Slide34INSTI Drug Interactions
Polyvalent cations (Al, Mg, Ca, Fe) may chelate with INSTIsEach INSTI has specific separation recommended (most separate by >2hrs)Avoid coadministration of raltegravir and aluminum or magnesium Max dose of metformin coadministered with dolutegravir is 1000mg QdayElvitegravir/cobicistat has many drug interactions as both are major substrates of CYP 3A4 and cobicistat is a strong CYP3A4 inhibitor
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/287/insti-drug-interactions
Slide35NNRTI Drug Interactions
Rilpivirine (RPV)requires acidic environment for absorptionmajor substrate of CYP3A4Antacids: give at least 2 hours before or 4 hours after RPVH2 blockers: give H2 blocker at least 12 hours before or 4 hours after RPVProton Pump Inhibitors: CONTRAINDICATED. Do not coadminister
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/285/nnrti-drug-interactions
Slide36PI Drug Interactions
Most PIs and boosters are major substrates of CYP 3A4 and strong CYP3A4 inhibitor = MANY DRUG INTERACTIONSCorticosteroids: coadministration can result in adrenal insufficiency and Cushing’s syndromeInhaled or intranasal corticosteroids: beclomethasone & flunisolide safeStatins: lovastatin & simvastatin contraindicatedAtorvastatin and rosuvastatin may be titrated and based on PI have a max dose recommendedContraindicated with some hepatitis C direct-acting antiviral agents
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/284/pi-drug-interactions
Slide37Slide38Facilitators and Barriers to Treatment
ART Adherence
Slide39Medication Adherence
Whether patients take their medications as prescribed and continue to take their medication correctly
Reasons why medication adherence can be difficult
Medication side effects
Busy schedule
Dose schedule
Medication cost
Illness or depression
Alcohol or drug use
Homelessness
Fear of others finding out patient has HIV
Slide40Medication Adherence Tools
Slide41Facilitators and Barriers to Treatment
Pharmacy
Team
Slide42Pharmacist Role in HIV Care
Adherence counseling (refill reminders, refill syncing, pill boxes, blister packs, alarms)Patient education (regarding dosing, adverse effects, drug interactions, missed doses)Maintain ART inventoryDispense complete regimensART regimen selectionMedication reconciliation at hospital admission and dischargeART safety monitoring (renal/hepatic dose adjustment, adverse effects, drug interactions)Opportunist infection prophylaxis and treatment monitoringProvider/pharmacy education Smoking cessation & other comorbidity managementReferrals
1. Saberi P, et al. Patient Preference and Adherence 2012; 6:297-322, 2. Schafer JJ, et al. Am J Health-Syst Pharm. 2016;73:468-94
Slide43Pharmacy Technician Role in HIV Care
Benefits investigationHelp with prior authorizationHelp maintain inventoryCopay assistance enrollmentRefill remindersAvoid HIV disclosure
Gilbert EM, et al. Am J Health-Syst Pharm. 2016;73:757-63
Slide44Slide45Conclusion
Only about 50% of individual living with HIV in the US are retained in care and have viral suppression
There are numerous safe and effective ART agents available
ART is complex in terms of increased numbers of agents and combinations, drug interactions, & high adherence rates required for virologic suppression
Pharmacy teams in various settings can impact and improve HIV care
Slide46The ART of HIV Management: An Antiretroviral Therapy Review
Sarah Pérez, PharmD, PhC, BCACP, AAHIVP