HIV Update 2017 GordonLA final - c.ymcdn.com · – ddC≥ ddI≥ d4T> AZT ≥ TDF≥ 3TC= FTC ≥...

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HIV Update 2017

Lori A. Gordon, PharmD, BCPS‐AQ ID, AAHIVP

Clinical Assistant Professor

Xavier University of Louisiana College of Pharmacy

LPA 2017.07.14

Disclosures• Lori A. Gordon, PharmD, reports the following disclosures:

– ViiV Healthcare (Regional Medical Advisory Board Expert)

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Pharmacists Learning Objectives• Following this presentation, the viewer should be able to:– Relate the steps of the HIV life cycle to targets of antiretroviral therapeutic classes

– Recommend appropriate complete regimens for treatment naïve HIV patients

– Identify common and unique adverse drug reactions within antiretroviral therapeutic classes

– Recognize potential mechanisms of drug‐drug interactions between antiretroviral agents and other concomitant medications

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Technicians Learning Objectives• Following this presentation, the viewer should be able to:

– Identify antiretroviral therapeutic classes required for complete regimens in treatment naïve HIV patients

– Identify common adverse reactions within antiretroviral therapeutic classes

– Identify common drug‐drug interactions between antiretroviral agents and other concomitant medications

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Natural Course of HIV Infection

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Rates of Diagnoses of HIV Infection among Adults and Adolescents, 2014—United States and 6 Dependent Areas

N = 44,609 Total Rate = 16.6

Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays, but not for incomplete reporting.

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Louisiana Statistics (2014)• Persons living with HIV: 20,627

– 52% with AIDS

• 2nd highest state in nation for new HIV diagnoses– Baton Rouge ranked highest and New Orleans ranked 2nd

highest among large metropolitan areas in nation for new HIV diagnoses

– Major risk factors• Men who have sex with men (MSM): 70%• African‐American: 71%• Youth/young adult: 31% (25 – 34yo); 27% (13 – 24yo);

• 2nd highest state in nation for new AIDS diagnoses– Baton Rouge ranked 1st; New Orleans ranked 4th

7LA OPH SHP 2015, www.hiv411.orgwww.aidsvu.org

• On average, I provide care to ___ HIV+ patients on a weekly basis

– 0 – 5

– 5 – 10

– 10 – 20

– 20+

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Hands up! The HIV Hijack

Targets for Antiretroviral Therapy

Life Cycle of HIV: Pharmacological Targets

• Binding

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• Binding

• Fusion/Penetration


• Binding


• Transcription

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• Binding


• Transcription

• Integration


• Binding


• Transcription

• Integration

• Translation

• Assembly/Budding/Maturation

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Life Cycle of HIV: Pharmacological Targets• Binding

– CCR5 antagonists

• Fusion/Penetration– Fusion inhibitors

• Transcription– Nucleoside/Non‐nucleoside

reverse transcriptase inhibitors (NRTI/nNRTI)

• Integration– Integrase strand transfer

inhibitors (InSTIs)

• Translation• Assembly/Budding/Maturation

– Protease inhibitors (PI)

Putting the cART before the horse

Recommended Antiretroviral Regimens

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Ms. Jones• Ms. Jones is a 26yo female who is newly diagnosed HIV+ patient.

– She is treatment‐naïve, with a baseline viral load of 893,000 copies/mL and CD4 count of 351 cells/mm3

• What would you select as an appropriate initial regimen for her?

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Combination AntiRetroviral Therapy (cART)

18Courtesy of AS Fauci

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Stage 3 (AIDS) Classifications and Deaths of Persons with HIV Infection Ever Classified as Stage 3 (AIDS), among Adults and

Adolescents, 1985–2013—United States and 6 Dependent Areas

Note. All displayed data have been statistically adjusted to account for reporting delays, but not for incomplete reporting. Deaths of persons with HIV infection, stage 3 (AIDS) may be due to any cause.

HIV Treatment Regimens

nNRTI

InSTI

NRTI Backbone(2 NRTIs)

PI

Anchor Drug

Department of Health & Human Services 2016

InSTI = integrase strand transfer inhibitornNRTI = non‐nucleoside reverse transcriptase inhibitorNRTI = nucleoside reverse transcriptase inhibitorPI = protease inhibitor

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Recommended Initial Regimens


Emtricitabine/Tenofovir

(FTC/TDF or FTC/TAF)

Abacavir/Lamivduine

(ABC/3TC)

Darunavir/ritonavir(DRV/rtv) Raltegravir

(RAL)

Dolutegravir(DTG)

Elvitegravir/cobicistat(EVG/cobi)

DTG

TAF = tenofovir alafenamideTDF = tenofovir disoproxil fumarate

A Superior Anchor Drug:The SINGLE Trial

22Walmsley SL, et al. N Engl J Med 2013

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A Superior Anchor Drug:The SINGLE Trial

23Walmsley SL, et al. N Engl J Med 2013

Atazanavir/ritonavir(ATV/rtv)

Alternative Initial Regimens


Rilpivirine^(RPV)

Efavirenz(EFV)

^ Pre‐treatment viral load < 100,000 copies/mL & CD4 count > 200 cells/mm3

TAF = tenofovir alafenamideTDF = tenofovir disoproxil fumarate

Atazanavir/cobicistat(ATV/cobi)

Darunavir/cobicistat(DRV/cobi)

DRV/rtv DRV/cobi

Emtricitabine/Tenofovir

(FTC/TDF or FTC/TAF)

Abacavir/Lamivduine

(ABC/3TC)

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ECHO & THRIVE: RPV vs. EFV

25Cohen CJ, et al. J Acquir Immune Defic Syndr 2012

– N = 1368 (ITT population)– 84% (RPV) vs. 82% (EFV) [95 CI ‐2.0% to 6.0%] at 48 weeks

Rilpivirine Virologic OutcomesAccording to Baseline Viral Load & CD4

26Complera prescribing information 2016

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Other Regimens:When an NRTI Backbone Cannot Be Used


^ Pre‐treatment viral load < 100,000 copies/mL & CD4 count > 200 cells/mm3

NRTI = nucleotide reverse transcriptase inhibitor

Lopinavir/ritonavir(LPV/rtv)

Lamivduine(3TC)

Raltegravir(RAL)^

Darunavir/ritonavir (DRV/rtv)^

Dual Therapy in Healthy Patients: The NEAT Study

28Raffi F, et.al. Lancet 2014

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INSTIs

Single Tablet Regimens Reduce Pill Burden

• Genvoya® (EVG/cobi/FTC/TAF)

• Stribild® (EVG/cobi/FTC/TDF)

• Triumeq® (DTG/3TC/ABC)

• Atripla® (EFV/FTC/TDF)

• Complera® (RPV/FTC/TDF)

• Odefsey® (RPV/FTC/TAF)

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NRTIs

NNRTIs

3TC = lamivudine; ABC = abacavir; cobi = cobicistat; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; FTC = emtricitabine; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

NRTIs

Fixed Dose Combination Tablets Reduce Pill Burden

• Epzicom® (ABC/3TC)

• Descovy® (FTC/TAF)

• Truvada® (FTC/TDF)

• Combivir® (3TC/AZT)

• Evotaz® (ATV/cobi)

• Prezcobix® (DRV/cobi)

• Kaletra® (LPV/rtv)

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NRTIs

PIs

3TC = lamivudine; ABC = abacavir; ATV = atazanavir; AZT = zidovudine; cobi = cobicistat; DRV = darunavir; FTC = emtricitabine; LPV = lopinavir; rtv = ritonavir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

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The Risk of Non‐Adherence• Genotype • Phenotype

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Ms. Jones• Ms. Jones is a 26yo female who is newly diagnosed HIV+ patient.

– She is treatment‐naïve, with a baseline viral load of 893,000 copies/mL and CD4 count of 351 cells/mm3

• What would you select as an appropriate initial regimen for her?

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A. Dolutegravir + abacavir + lamivudine

A. Darunavir + cobicistat + emtricitabine + tenofovir

A. Efavirenz + emtricitabine + tenofovir

A. Elvitegravir + cobicistat + abacavir + lamivudine

A. Rilpivirine + emtricitabine + tenofovir

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A. Dolutegravir + abacavir + lamivudine

A. Darunavir + cobicistat + emtricitabine + tenofovir

A. Efavirenz + emtricitabine + tenofovir

A. Elvitegravir + cobicistat + abacavir + lamivudine

A. Rilpivirine + emtricitabine + tenofovir

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First, do no harm

Potential Adverse Drug Reactions

Nucleoside Reverse Transcriptase Inhibitors:The “d” Drugs & Mitochondrial Toxicity

• Inhibition of mitochondrial DNA polymerase (pol γ)– Decreased mitochondrial DNA copy number, diminished ATP pools– ddC ≥ ddI ≥ d4T > AZT ≥ TDF ≥ 3TC = FTC ≥ ABC

• Clinical Manifestations– Boxed warning: Lactic acidosis and severe hepatomegaly with hepatic

steatosis– Pancreatitis– Peripheral neuropathy– Lipodystrophy

• Clinical relevance?– Predominantly with “d‐drugs” ± AZT

• Stavudine, d4T (Zerit®)• Didanosine, ddI (Videx®)• Zalcitabine, ddC (Hivid®)

36Koczor CA, et.al Expert Opin Drug Metab Toxicol 2010

NRTIs

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Nucleoside Reverse Transcriptase Inhibitors

Drug Adverse Drug Reactions

3TC^/FTC#• Skin hyperpigmentation• Hepatitis B related hepatic flare

ABC• Hypersensitivity reaction (fever, rash, malaise, GI/respiratory

symptoms)• Increased risk of MI?

AZT*• Bone marrow suppression (macrocytic anemia, neutropenia)• GI intolerance• Nail hyperpigmentation

TAF*/TDF^

• Nephrotoxicity• Renal proximal tubulopathy (hypophoshatemia, glucosuria [with

normoglycemia], hypouricemia proteinuria, sCr elevation)• Decreased bone mineral density• Hepatitis B related hepatic flare

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Department of Health & Human Services 2016Genvoya prescribing information 2017Vemlidy prescribing information 2017

^ Requires dose adjustment if CrCl < 50 mL/min# Requires dose adjustment if CrCl < 30 mL/min* Requires dose adjustment if CrCl < 15 mL/min

NRTIs

Abacavir Hypersensitivity: The PREDICT‐1 Study

• Comparison of HLA‐B*57:01 screening vs. abacavir skin patch test– Positive predictive value: 58%

• If you are HLA‐B*57:01(+) it is possible to develop hypersensitivity reaction (HSR)

• Likely additional genes involved in the development of HSR

– Negative predictive value: 100%• If you are HLA‐B*57:01(‐) it is unlikely to develop HSR

38Mallal S, et.al. N Engl J Med 2008

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Abacavir & Myocardial InfarctionThe D:A:D Collaboration

• International, prospective, observational cohort– 33,308 patients

• 178,835 person‐years (PYs)

– Evaluated incident cases of MI• Recent exposure to ABC associated with increased risk of MI (RR 1.70)

• Cumulative exposure to ABC associated with increased risk of MI (RR 1.07)

• Higher burden if pre‐existing cardiac risk factors

• Remains controversial– Studies with similar vs. weak/no association

39Sabin CA, et.al. Lancet 2008Worm SW, et.al. J Infect Dis 2010ABC = abacavir; MI = myocardial infarction; RR = relative risk

A Tale of Two Prodrugs: TDF vs TAF

40TAF = tenofovir alafenamideTDF = tenofovir disoproxil fumarate Callebaut C, et.al. Antimicrob Agents Chemother 2015

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Choose TAF over TDF: Renal Markers

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Wohl D, et.al. J Acquir Immune Defic Syndr 2016

Choose TAF over TDF: Bone Mineral Density

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Wohl D, et.al. J Acquir Immune Defic Syndr 2016

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Integrase Strand Transfer Inhibitors

Drug ADRs

DTG• Non‐progressive sCr elevation (via OCT2 inhibition)• Neuropsychiatric symptoms (insomnia, depression)• Hypersensitivity reaction

EVG/cobi• Nausea• Diarrhea• Neuropsychiatric symptoms (depression)

RAL• Rash (including Stevens‐Johnson syndrome)• CPK elevation/muscle weakness• Neuropsychiatric symptoms (depression)

43Department of Health & Human Services 2016

INSTIs

Integrase Strand Transfer Inhibitors & Neuropsychiatric Events: The OPERA data

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Fettiplace A, et.al. J Acquir Immune Defic Syndr 2017DRV = darunavir; DTG = dolutegravirEFV = efavirenz; RAL = raltegravir

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Protease Inhibitors: Out with the Old…

Drug ADRs

3TC/FTC• Skin hyperpigmentation• Hepatitis B related hepatic flare

ABC• Hypersensitivity reaction• Increased risk of MI?

AZT• Bone marrow suppression (macrocytic anemia, neutropenia)• GI intolerance• Nail hyperpigmentation

TDF

• Renal proximal tubulopathy (hypophoshatemia, glucosuria (with normoglycemia, hypouricemia proteinuria, sCr elevation)

• Decreased bone mineral density• Hepatitis B related hepatic flare


Drug ADRs

Fosamprenavir (FPV)• Rash (sulfonamide moiety)• Nephrolithiasis

Indinavir (IDV) • Nephrolithiasis

Lopinavir/ritonavir (LPV/r)• GI intolerance• Hyperlipidemia (hyperTG)• PR/QT prolongation

Nelfinavir (NFV)• Diarrhea• LFTs elevation

Saquinavir (SQV)• PR/QT prolongation• LFTs elevation

Tipranavir (TPV)• Hepatotoxicity• Rash (sulfonamide moiety)• Intracranial hemorrhage

PIs

Protease Inhibitors:…In With the New

Drug ADRs

Atazanavir(ATV) rtv

• GI intolerance• Hyperlipidemia• Hyperglycemia

• Indirect hyperbilirubinemia• Nephrolithiasis• Cholethiaisis• Rash (sulfate moiety)• PR prolongation/1° AV block

Darunavir(DRV)

• Hepatotoxicity/LFTs elevation• Rash (sulfonamide moiety)


PIs

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Non‐Nucleoside ReverseTranscriptase Inhibitors

Drug ADRs

EFV

• Neuropsychiatric symptoms (vivid dreams/nightmares, dizziness, suicidal ideation/attempt/completion)

• Rash• Teratogenicity (D/C/C)• False positive tests (cannabinoid, benzodiazepine)

RPV• Rash• Neuropsychiatric symptoms (depression, insomnia, headache)

Etravirine(ETR)

• Rash• Hypersensitivity reaction


NNRTIs

DDI… not ddI

Drug‐Drug Interactions

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Mr. Smith• Mr. Smith is a 54yo patient who has been living with HIV for the past 10 years. – He is currently virologically suppressed on DRV/cobi + FTC/TAF with a high CD4 count.

– His past medical history includes:• GERD

• Hyperlipidemia (ASCVD 10‐yr risk = 13.5%)

• HCV

• Seasonal allergies

• How would you appropriately manage his other chronic co‐morbidities?

49ASCVD = atherosclerotic cardiovascular disease; cobi = cobicistat; DRV = darunavir; FTC = emtricitabine; GERD = gastroesophageal reflux disease; HCV = hepatitis C; TAF = tenofovir alafenamide

The Pharmacokinetics of An Oral Dose of Medication

50Courtesy of SR Penzak

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The Pharmacokinetics of Therapy: Concentration vs Time Curve

51Courtesy of A Pau

OVERALL DRUG EXPOSURE

TROUGH

CMAX

Food & Antiretroviral Interactions• Take with food

– elvitegravir

– etravirine

– rilpivirine

– atazanavir

– darunavir

– lopinavir/ritonavir

• Take on an empty stomach

– efavirenz

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DRUG LEVELS

SIDE EFFECTS

SIDE EFFECTS


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Acid Reducing Agents & Antiretrovirals

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* without concomitant TDF

ATV

Directions Treatment‐Naïve Treatment‐Experienced

AntacidsGive ATV 2h before/1h after

ATV 400mgATV 300mg + RTV 100mg

ATV 400mgATV 300mg + RTV 100mg

H2RAsGive ATV simultaneously or 2h before/10h after

ATV 400mgNot to exceed famotidine 20mg PO bid‐‐‐ATV 300mg + RTV 100mgNot to exceed famotidine 40mg PO bid

ATV 300mg + RTV 100mg*

ATV 400mg + RTV 100mg

Not to exceed famotidine 20mg PO bid

PPIs Give ATV 12 afterATV 300mg + RTV 100mgNo to exceed omeprazole 20mg PO daily

Do not co‐administer

RPV

AntacidsGive RPV 4h before/2h after

RPV 25mg

H2RAsGive RPV 4h before/12h after

RPV 25mg

PPIs ‐‐‐ Do not co‐administer


Integrase Strand Transfer Inhibitors & Polyvalent Cations

• Al3+, Ca2+, Fe2+/3+, Mg2+, Zn2+

– Give INSTI 2h before (4 – 6 hours after) polyvalent cations*^&

• Potential sources:

– Antacids

– Laxatives

– Multivitamins/supplements

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^ no need to separate DTG from Ca2+ or Fe2+/3+ if given with food* no need to separate administration of RAL and Ca2+& do not co‐administer RAL and Al3+ Department of Health & Human Services 2016

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Types of Metabolism• Phase I/Oxidation

– Increases water solubility

– Mediated by Cytochrome P450 (CYP450) enzyme family

• CYP3A4 responsible for 82% of CYP‐mediated drug elimination

• Phase II/Conjugation

– Renders pharmacologically inactive

• Attach additional chemical group to drug

– Mediated by uridine diphosphateglucuronosyltransferase (UGT)

55Galetin et.al. Exp Opin Drug Metab Toxicol 2008

CYP Inhibition


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CYP Induction


Exploiting CYP3A Inhibition

58van Heeswijk RPG, et.al. AIDS 1999

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Pharmacokinetic Boosting Agents:Ritonavir & Cobicistat

59Mathias A, et.al. IWCPHT 2010GS‐9350 = cobicistat; RTV = ritonavir

COBI Considerations: ATV/c & DRV/c

60Gallant JE et.al. J Infect Dis 2013

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ARV CYP Mechanism of Interactions

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InducersInhibitors Substrates

3A4ATV cobi*

DRV EFVETR EVGRPV rtv

2B6 2D6 2C9/2C19EFV rtv ETR

3A4EFVETR

1A2RTV2B6

EFV, rtv2C9/2C19

rtv

3A4ATVcobi*DRVrtv

2C9/2C19EFV, ETR2D6COBI*

* COBI is not an antiretroviral Department of Health & Human Services 2016

Anti‐infectives: Rifamycins• asda

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ARV Rifampin Rifabutin Dosing Recommendations

Protease Inhibitors

PI Cmin: >75% Rif AUC: > 100%Rifampin: Do not co‐administerRifabutin: 150mg/day or 300mg 3x/week

EFV EFV AUC: 26% Rif AUC: 38%Rifampin: 600mg/day; EFV 600mg/day Rifabutin: 450 – 600 mg/day; EFV 600mg/day

ETR ETR possibleRif AUC: 17%ETR AUC: 37%

Rifampin: Do not co‐administerRifabutin: 300 mg/day*; ETR 200mg BID

RPV RPV AUC: 80% RPV AUC: 46%Rifampin: Do not co‐administerRifabutin: 300mg/day; RPV 50mg/day

RAL RAL AUC: 40% RAL AUC: 19%Rifampin: 600mg/day; RAL 800mg BIDRifabutin: 300mg/day; RAL 400mg BID

EVG/c EVG possibleEVG Cmin: 67%

Rif’ AUC: > 600%Rifampin: Do not co‐administerRifabutin: Do not co‐administer

DTG DTG AUC: 54% DTG Cmin: 30%Rifampin: 600mg/day; DTG 50mg BID^Rifabutin: 300mg/day; DTG 50mg/day^

MVC MVC AUC: 64% MVC possibleRifampin: Use only if necessary; MVC 600mg BID (MVC 300mg BID#)Rifabutin: 300mg once daily (MVC 150mg BID#)

* without concomitant PI# with concomitant PI^ unless certain INSTI RAMs ‘ 25‐O‐desacetyl‐rifabutin (metabolite)

Department of Health & Human Services 2016Complera prescribing information 2016

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Anti‐infectives: Azolesand CYP 3A4 Modulators

63

CYP3A4 Metabolism

SubstrateMinor Moderate Major

Voriconazole Itraconazole Isavuconazonium

RecommendationVoriconazole 400mg BID + EFV 300mg/day

Monitor itraconazolelevels^ (especially if

>200mg/day)

Caution in co‐administration

(consider alternative?)

^ Do not co‐administer with EFV Department of Health & Human Services 2016

Inhibitor

Weak Moderate Strong

Fluconazole IsavuconazoniumPosaconazoleVoriconazole

RecommendationNo adjustment

necessary(see recommendation

above)

Monitor for ARV‐related toxicities; co‐administer if benefit outweighs risk^

Anti‐infectives: Hepatitis C

64Department of Health & Human Services 2016Harvoni prescribing information 2017

ATV = atazanavir; cobi = cobicistat; DCV = daclatasvir; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; LPV = lopinavir; RAL = raltegravir; RPV = rilpivirine; TAF = tenofoviralafenamide; TDF = tenofovir disoproxil fumarate; rtv = ritonavir

Anti‐retrovirals

Direct Acting Antivirals

DaclatasvirElbasvir/

GrazoprevirLedipasvir/ Sofosbuvir

Ombitasvir/Paritaprevir/rtv +

DasabuvirSimeprevir

Velpatasvir/ Sofosbuvir

ATVdecrease DCV dose

✗ ✔ use ATV 300mg(no additional booster)

✗ ✔

DRV✔ ✗ ✔ ✗ ✗ ✔

DTG ✔ ✔ ✔ ✔ ✔ ✔

EFVincrease DCV dose

✗ ✔ ✗ ✗ ✗

ETRincrease DCV dose

✗ ✔ ✗ ✗ ✗

EVG/cobidecrease DCV dose

✗ ✔ ✗ ✗ ✔

LPV/rtv ✔ ✗ ✔ ✗ ✗ ✔

RAL ✔ ✔ ✔ ✔ ✔ ✔

RPV ✔ ✔ ✔ ✔ ✔

TAF ✔ ✔ ✔ ✔ ✔ ✔

TDF ✔ ✔ caution ✔ ✔ caution

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HMG‐CoA Reductase Inhibitors (“statins”) and CYP 3A4 Inhibitors

65

CYP Metabolism

3A4 (3A4) Mixed Non‐CYP (UGT)

LovastatinSimvastatin

PravastatinAtorvastatin (3A4, UGT)

Fluvastatin (3A4, 2C9, 2D6)Rosuvastatin (3A4, 2C9)

Pitavastatin

Do not co‐administer

No adjustment necessary

Titrate carefully and use lowest necessary dose

No adjustment necessary


Phosphodiesterase‐5 (PDE‐5) Inhibitors and CYP 3A4 Inhibitors

66

PDE‐5 Inhibitor

Recommendation

Avanafil • Do not co‐administer

Sildenafil• 25mg q48h (erectile dysfunction)• Do not co‐administer (for PAH)

Tadalafil• 5 10mg q72h (erectile dysfunction)• 20 40mg once daily (PAH)• 2.5mg once daily (BPH)

Vardenafil • 2.5mg q72h (erectile dysfunction)

Benign prostatic hyperplasia (BPH); Pulmonary arterial hypertension (PAH) Department of Health & Human Services 2016

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Neuropsychiatric Medications &and CYP 3A4 Modulators

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CYP Metabolism

Only non‐3A4 3A4 (minor) 3A4 (major)

Substrate

LamotriginePhenobarbitalValproic acidOxazepamParoxetineLorazepam

AmitriptylinePhenytoin*BupropionSertaline

Temazepam

AlprazolamDiazepam

CarbamazepineClonazepamEthosuximideQuetiapine#


necessaryTitrate dose of substrate based on clinical response

Consider alternative or monitor levels/effectiveness

of substrate

Induction Valproic acid

CarbamazepinePhenobarbitalPhenytoin

Oxcarbazepine


necessaryConsider alternative or monitor levels of ARV^

^ Do not co‐administer with PI without RTV, ETR, or RPV* Consider alternative/levels (narrow therapeutic index)# Reduce quetiapine dose by 1/6 if starting PI Department of Health & Human Services 2016

DRUG CLASS: Anti‐depressant; Anti‐epileptic; Anti‐psychotic; Benzodiazepine

Hormonal Contraceptives

68

ARV Contraceptive Dosing Recommendations

Estrogen

ATV/r & DRV/r Ethinyl estradiol AUC: 19 – 44%^

Recommend alternative/additionalcontraception

EFV Ethinyl estradiol AUC: no change

EVG/c/FTC/TDF Ethinyl estradiol AUC: 25%

ETR Ethinyl estradiol AUC: 22%No adjustment necessary

RPV Ethinyl estradiol AUC: 14%

Progesterone

ATV/r & DRV/r Norethindrone AUC: 14 – 34%^

Recommend alternative/additionalcontraception

EFV Levonorgestrel AUC: 58 – 83%*

EFV Etonogestrel AUC: 63%

EVG/c/FTC/TDF Norgestimate AUC: > 200%

^ Without RTV boosting, AUC increase* Case reports of contraceptive failure with implants

Department of Health & Human Services 2016Scarsi KK, et.al. CROI 2014Perry SH, et.al. AIDS 2014

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Local Corticosteroidsand CYP 3A4 Inhibitors

69

Ramanathan R, et.al. Clin Infect Dis 2008

Local Corticosteroidsand CYP 3A4 Inhibitors

70Boyd SD et.al. J Acquir Immune Defic Syndr 2013

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Types of Transport

Ayrton A, et.al. Xenobiotica 2001

Breast cancer resistance protein (BCRP); Multi‐drug resistance‐associated protein (MRP); Organic anion transporting polypeptide (OATP); Organic anion transport (OAT); Organic cation transport (OCT); P‐glycoprotein (P‐gp, also ABC)

Limit Metformin Dose with Dolutegravir

72

Song IH, et.al. J Acquir Immune Defic Syndr 2016

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Mr. Smith• Mr. Smith is a 54yo patient who has been living with HIV for the past 10 years. – He is currently virologically suppressed on DRV/r + FTC/TDF with a high CD4 count.

– His past medical history includes:• GERD

• Hyperlipidemia (ASCVD 10‐yr risk = 13.5%)

• HCV

• Seasonal allergies

• How would you appropriately manage his other chronic co‐morbidities?

73

• Can Mr. Smith receive a PPI with his cART?– Yes

• Which HMG‐CoA reductase inhibitor would be best for Mr. Smith?– Atorvastatin– Rosuvastatin

• Which HCV medications should Mr. Smith avoid?– Ledipasvir– Paritepravir (+ Ombitasvir + Dasabuvir)– Simeprevir

• Which corticosteroid intranasal spray would you recommend for Mr. Smith?– Beclomethasone

74

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Conclusions• Combination antiretroviral therapy results in HIV virologic suppression, leading to increased longevity and quality of life

• Recommended and alternative antiretroviral regimens are generally well tolerated– Patients should be educated regarding hallmark adverse drug reactions that may commonly or rarely occur

• As patients age with HIV, it is important to conduct a comprehensive medication review to reconcile potential drug‐drug interactions.

75

Questions?

Lori A. Gordon, PharmD, BCPS, AAHIVP

Xavier University of Louisiana College of Pharmacy

[email protected]

HIV Update 2017 GordonLA final - c.ymcdn.com · – ddC≥ ddI≥ d4T> AZT ≥ TDF≥ 3TC= FTC ≥...

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Transcript of HIV Update 2017 GordonLA final - c.ymcdn.com · – ddC≥ ddI≥ d4T> AZT ≥ TDF≥ 3TC= FTC ≥...