2016 hiv t u · 2018-04-01 · 2016 hiv treatment update john m. conry, pharm.d., aahivp, fnap...

2016 HIV TREATMENT UPDATE

John M. Conry, Pharm.D., AAHIVP, FNAP

Clinical Professor and Assistant Dean

College of Pharmacy and Health Sciences, St. John’s University

Clinical Coordinator of Pharmaceutical Care Services, Project Renewal

Pharmacist Champion, NYSDOH Clinical Education Initiative

I have no relevant disclosures

DISCLOSURE

1. Discuss the current epidemiology of HIV/AIDS in the US

2. Apply the current treatment guidelines for the management of HIV/AIDS in antiretroviral-naïve

patients

3. Discuss opportunities for pharmacists to assist HIV-infected patients, who are initiating

antiretroviral therapy, in attaining treatment goals

LEARNING OBJECTIVES:

4

Dynamic Face of HIV

http://en.wikipedia.org/wiki/Image:Magic_johnson_book_cover.jpg

http://en.wikipedia.org/wiki/Image:ArthurAshe.jpeg

http://en.wikipedia.org/wiki/Image:RockHudson.jpg

Plan to End the AIDS Epidemic in NYS by End of Year 2020

1. Identifying persons with HIV who remain undiagnosed and linking them to health care.

2. Linking and retaining persons diagnosed with HIV to health care and getting them on anti-HIV therapy to maximize HIV virus suppression so they remain healthy and prevent further transmission.

3. Providing access to Pre-Exposure Prophylaxis (PrEP) for high-risk persons to keep them HIV negative.

Management of HIV/AIDS in 1987

8

Management of HIV in 1996

Fasting (1 hour before/2 hours after meals) 1.5 liters of hydration/day

8AM 4PM 12 MID

10

Management of HIV in 2016(All in One Combination Tablets)

Atripla Stribild Complera Triumeq

Genvoya Odefsey

11UNAIDS 2010 Global Report

Global summary of the AIDS epidemic 2014

36.9 million [34.3 million – 41.4 million]






220 000 [190 000 – 260 000]

1.2 million [980 000 – 1.6 million]

1.0 million [760 000 – 1.8 million]

150 000 [140 000 – 170 000]

Number of people

living with HIV

People newly infected

with HIV in 2014

AIDS deaths in 2014

Total

Adults

Women

Children (<15 years)

Total

Adults


Total

Adults


www.unaids.org July 2015- Core Epidemiology Slides

Total: 36.9 million [34.3 million – 41.4 million]

Middle East & North Africa240 000

[150 000 – 320 000]

Sub-Saharan Africa25.8 million

[24.0 million – 28.7 million]

Eastern Europe & Central Asia1.5 million


Asia and the Pacific5.0 million


North America and Western and Central Europe2.4 million


Latin America1.7 million


Caribbean280 000

[210 000 – 340 000]

Adults and children estimated to be living with HIV 2014


About 5,600 new HIV infections a day in 2014

About 66% are in Sub Saharan Africa

About 600 are in children under 15 years of age

About 5,000 are in adults aged 15 years and older, of whom:─ almost 48% are among women

─ about 30% are among young people (15-24)


CDC HIV/AIDS Facts-

July 2015 (www.cdc.gov)15

US HIV/AIDS Epidemiology

• 1.2 million US residents living with HIV

– 13% don’t know their HIV-infected

• Approximately 50,000 new HIV-infections/year

• 658,507 US residents have died from HIV/AIDS

• Majority of persons living with HIV

– MSM (4% of male population, 78% of new infx)

– African-Americans (12% population, 44% of new infx)

– Hispanics/Latinos (16% population, 20% of new infx)

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.

Diagnoses of HIV Infection among Adults/Adolescents, by Sex and

Transmission Category, 2014—United States and 6 Dependent Areas

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 and missing transmission category, but not for incomplete reporting.

a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.

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.

19

Screening/Diagnosis of HIV• Standard Blood Test

– ELISA: screening test

– Western Blot: confirmatory test

• OraQuick- Rapid Tests (OTC)

• Home Access Express HIV-1 Test (OTC)

• In emergency situations- Viral Load

20www.aidsinfo.nih.gov

www.aidsinfo.nih.gov 21

www.aidsinfo.nih.gov 22

23

Pathology of HIV

Fauci AS et al. Ann Intern Med.

1996;124:654-63

24

CD4+ and Viral Load

CD4

• Measure of patients immune function

– cells/mm3

VL

• Measure of virus in blood

– copies of virus/ml of blood

25

Pharmacotherapy Options

• Nucleoside/Nucleotide Reverse Transcriptase Inhibitors– “Nukes”, NRTI’s

• Non-nucleoside Reverse Transcriptase Inhibitors– “Non-nukes”, NNRTI’s

• Protease Inhibitors (PI’s)

• Entry Inhibitors

– Fusion Inhibitor

– CCR5 Antagonist

• Integrase inhibitors

26

NRTI’s• Zidovudine (AZT) (Retrovir®)

• Didanosine (ddI) (Videx EC®)

• Stavudine (d4T) (Zerit®)

• Lamivudine (3TC) (Epivir®)

• Abacavir (ABC) (Ziagen®)

• Tenofovir (TDF) (Viread®)

• Emtricitabine (FTC) (Emtriva®)

• Combination Tablets– Combivir®: AZT + 3TC – Epzicom®: ABC + 3TC– Truvada®: TDF + FTC– Descovy®: TDF + FTC– Trizivir®: AZT + 3TC + ABC

• Other Combos including NRTIs– Atripla®:

• Efavirenz + TDF + FTC

– Complera®:• Rilpivirine + TDF + FTC

– Odefsey®:• Rilpivirine + TAF + FTC

– Stribild®:• Elvitegravir + COBI +TDF + FTC

– Genvoya®:• Elvitegravir + COBI +TAF + FTC

– Triumeq®: • Dolutegravir + ABC + 3TC

27

NRTI Dosing/AdministrationGeneric

Name

Brand Name Usual Dosing

Food Notes

Abacavir

(ABC)

Ziagen

Trizivir

Epzicom

Triumeq

QD/BID

BID

QD

QD

With or without

EtOH ABC levels

Didanosine

(ddI)

Videx EC QD

( wt)

1 hr b/f or 2 hrs after meal

*renal

Emtricitabine

(FTC)

Emtriva

Truvada

Descovy

Atripla

Complera

Odefsey

Stribild

Genvoya

QD

QD

QD

QD

QD

QD

QD

QD

With or without

(*Atripla/ Complera/ Odefsey/ Stribild/ Genvoya)

* renal

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NRTI Dosing/Administration (cont’d)

Generic

Name

Brand Name

Usual Dosing

Food Notes

Lamivudine

(3TC)

Epivir

Combivir

Trizivir

Epzicom

Triumeq

QD/BID

BID

BID

QD

QD

With or without

*renal

Stavudine

(d4T)

Zerit BID

( wt)

With or without

*renal

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NRTI Dosing/Administration (cont’d)

Generic

Name


Food Notes

Tenofovir

(TDF and TAF)

Viread

Truvada

Descovy (TAF)

Atripla

Complera

Odefsey (TAF)

Stribild

Genvoya* (TAF)

QD

QD

QD

QD

QD

QD

With or without

(*Atripla/ Complera/ Odefsey Stribild/ Genvoya)

*renal

Zidovudine (AZT/ZDV)

Retrovir

Combivir

Trizivir

BID/TID

BID

BID

With or without

*renal

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“Class” NRTI- Important Notes

• Elimination– Generally require dosage adjustment for renal insufficiency– Atripla, Combivir, Trizivir, Epzicom are not for patients with CrCl <50

ml/min– Truvada is not for patients with CrCl <30 ml/min

• Side Effects– [Rare but serious cases of lactic acidosis and severe hepatomegaly

with steatosis reported with most NRTI’s] – Hepatotoxicity– GI intolerance (nausea, vomiting, diarrhea)– HIV/HBV co-infected patients may develop severe hepatic flares when

TDF, 3TC and FTC are withdrawn or resistance

* [brackets]- denotes black box warnings

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Select NRTI Significant Side Effects

Abacavir [Hypersensitivity Syndrome], hyperlipidemia, risk MI?

Didanosine [Pancreatitis], PN, non-cirrhotic portal HTN, insulin resistance, risk MI?

Stavudine [Pancreatitis], PN, lipoatrophy, hyperlipidemia, G-B, insulin resistance

Tenofovir Nephrotoxicity, asthenia, h/a, GI, osteopenia

(TAF- less kidney and bone problems)

Zidovudine [severe anemia, neutropenia][myopathy], lipoatrophy, hyperlipidemia, insulin resistance

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NNRTI’s

• Delavirdine (Rescriptor®)

• Efavirenz (Sustiva®)

– Combination available: Atripla®

• Nevirapine (Viramune and XR®)

• Etravirine (Intelence®)

• Rilpivirine (Edurant®)

– Combination available: Complera®, Odefsey®

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NNRTI Dosing/AdministrationGeneric

Name

Brand Name

Usual Dosing

Food Notes

Delavirdine

(DLV)

Rescriptor TID With or without

*Separate antacids

*CYP 450 interactions

Efavirenz

(EFV)

Sustiva

Atripla

QD (HS)

QD (HS)

Empty stomach

* CYP 450 interactions

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NNRTI Dosing/AdministrationGeneric

Name

Brand Name

Usual Dosing

Food Notes

Nevirapine (NVP)

Viramune

Viramune XR

qd x14d, then BID

qd

With or without


Etravirine (ETV)

Intelence BID Take following a meal


Rilpivirine (RPV)

Edurant

Complera

Odefsey

QD

QD

QD

With food * CYP 450 interactions

** PPI

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“Class” NNRTI- Important Notes• Elimination

– Beware of drug interactions• All are CYP 450 substrates

• Depending on the NNRTI may have the ability to inhibit and/or induce CYP 450 enzymes

• Side Effects- particularly with nevirapine

– Skin rash and Stevens-Johnson Syndrome/Toxic Epidermal Necrosis- rare but serious

– Osteopenia/osteoporosis

– Hepatotoxicity

– GI intolerance (nausea, vomiting, diarrhea)

36

Select NNRTI Significant Side Effects

Delavirdine GI upset, neutropenia

Efavirenz CNS disturbances, lipodystrophy, hyperlipidemia, false + cannabinoid test, teratogenic in animal studies

Nevirapine [Hepatotoxicity, particularly tx-naïve women w/ CD4 > 250 & men >400], [Skin Rash (SJS)]; [dosing titration]

Etravirine Rash, headache, GI, hypersensitivity

Rilpivirine Rash, CNS (depression, insomnia), lipodystrophy

37

PI’s

• Saquinavir (Invirase®)

• Ritonavir (Norvir®)– The “boosting” PI

• Indinavir (Crixivan®)

• Nelfinavir (Viracept®)

• Lopinavir/Ritonavir (Kaletra®)

• Atazanavir (Reyataz®)– Atazanavir/COBI (Evotaz®)

• Fosamprenavir (Lexiva®)

• Tipranavir (Aptivus®)

• Darunavir (Prezista®)– Darunavir/COBI (Prezcobix®)

38

PI Dosing/Administration

Generic

Name


Food Notes

Atazanavir (ATV)

Reyataz

Evotaz

QD

QD

With food (avoid antacid)

*acidic medium


Darunavir (DRV)

Prezista

Prezcobix

QD/BID (give with RTV)

QD

With food *sulfa


39


Generic

Name

Brand Name

Usual Dosing

Food Notes

Fos-amprenavir

(FPV)

Lexiva QD/BID

(depends if naïve)

With or without


*sulfa

Indinavir (IDV) Crixivan Q 8 hrs or

(+ RTV= q 12)

w/o RTV

Empty stomach

w/ RTV

w or w/o

* fluids


40


Generic

Name


Food Notes

Lopinavir/ RTV

(LPV/r)

Kaletra QD/BID

(depends if naïve)

With or Without


Nelfinavir (NFV)

Viracept BID/TID With food * CYP 450 interactions

Ritonavir (RTV)

Norvir QD/BID

(booster)

With food Refrigerate capsules


41


Generic

Name

Brand Name

Usual Dosing Food Notes

Saquinavir (SQV)

Invirase BID(+RTV) With food


Tipranavir

(TPV)

Aptivus BID (give with RTV)

With food

*sulfa

*refrigerated caps


42

“Class” PI- Important Notes

• Elimination

– Metabolized by CYP 450

– Beware of drug interactions

• All are CYP 450 substrates and inhibitors of CYP 3A4

• Degree of inhibition varies with the different protease inhibitors

• Chronic Long Term Use Can Lead to Significant Side Effects

– GI intolerance (nausea, vomiting, diarrhea)

– Hepatotoxicity

– Hyperlipidemia (less with atazanavir/darunavir)- premature CAD?

– Hyperglycemia/Insulin resistance/ Type 2 DM (less with atazanavir)

– Body fat changes- lipodystrophy

– Bleeding episodes in patients with hemophilia

– Osteopenia/Osteoporosis

43

PI Significant Side Effects

Atazanavir Indirect hyperbilirubinemia, EKG-prolong PR interval, nephrolithiasis, Skin Rash, SJS/TEN

Darunavir Skin Rash, SJS/TEN, hepatotoxicity

Fosamprenavir Skin Rash, SJS/TEN, hepatotoxicity

Indinavir Nephrolithiasis, Indirect hyperbilirubinemia, SJS/TEN

44

PI Significant Side Effects

Lopinavir/RTV GI intolerance ( with qd), Hyperlipidemia (TG), EKG- prolong PR interval, SJS/TEN

Nelfinavir Diarrhea

Ritonavir [Drug Interactions], Significant GI distress, circumoral/ extremity paresthesias, alteration in taste

Tipranavir Skin Rash, [Hepatotoxicity], [Intracranial hemorrhage], Hyperlipidemia (TG)

Entry Inhibitors

• Enfuvirtide (Fuzeon®)

– Fusion Inhibitor

• Maraviroc (Selzentry®)

– CCR5 Antagonist

45

46

Entry Inhibitor Dosing/Administration

Generic

Name

Brand Name

Usual Dosing

Food Notes

Enfuvirtide(ENF)

Fuzeon BID (sub-cutaneous injection)

With or without

Teaching needed for injection technique

Maraviroc

(MVC)

Selzentry BID With or without


* Need for tropism testing

47

Select Entry Inhibitor Significant Side Effects

Enfuvirtide Injection site reactions, GI distress, hypersensitivity, bacterial pneumonia

Maraviroc Upper respiratory infections, fever, cough, GI distress, orthostatic hypotension, dizziness, [HSR-hepatotoxicity], musculoskeletal symptoms

Integrase Inhibitors

• Raltegravir (Isentress®)

• Elvitegravir (Vitekta®)• Elvitegravir + COBI +TDF + FTC (Stribild®)

• Elvitegravir + COBI +TAF + FTC (Genvoya®)

• Dolutegravir (Tivicay®)• Dolutegravir + ABC + 3TC (Triumeq®)

48

49

Integrase Inhibitor Dosing/Administration

Generic

Name

Brand Name

Usual Dosing

Food Notes

Raltegravir (RAL)

Isentress BID With or without

*UGTA1A1 Glucoronidation

*Use restricted to those with CrCl >70ml/min

Elvitegravir (EVG)

Vitekta

Stribild

Genvoya

QD with PI/r

QD

QD

With food * CYP 450 interactions

Dolutegravir (DTG)

Tivicay

Triumeq

QD or BID

QD

With or without

*CYP 450 and binding interactions

50

Integrase Inhibitor Significant Side Effects

Raltegravir Common: Insomnia, h/a, GI distress

Serious: HSR, myopathy/rhabdomyolysis, SJS/TEN

Elvitegravir Common: h/a, GI distress

Serious: Proximal renal tubulopathy

Dolutegravir Common: h/a, insomnia

Serious: HSR, abnormal liver function

51

Antiretroviral-Related Factors Counseling Points

• Adherence

• Allergy History

• Dosing

• Administration

• Storage

• Adverse Effects

• Drug Interactions

52

Key Factors

Choosing Antiretroviral Therapy

CD4 countViral Load

ConcomitantMedications/ Herbs/ OTCPatient

Acceptance/Readiness

PriorTherapy -

Resistance

Patient’sClinicalStatus

Baseline Labs

HAART Efficacy/Toxicity

53

HIV Therapeutic Guidelines

• Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 28, 2016. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf

• International Antiviral Society-USA Panel. 2014 Recommendations for Antiretroviral Treatment of Adult HIV Infection. JAMA. 2014;312(4):410-425. Published July 23, 2014.

• NYS DOH AIDS Institute (www.hivguidelines.org)

DHHS HIV Treatment Guidelines 54

Goals of Therapy and Strategies to Achieve These Goals

Goals

• Maximal and durable suppression of VL

• Restoration and/or preservation of immunologic function

• Improvement of QOL

• Reduction in HIV-related morbidity & mortality

• Prevent HIV transmission

Strategies

• Pretreatment drug resistance testing

• Selection of HAART

• Maximize adherence

55

HIV Laboratory Assessment

• CD4 cell count and Viral load (HIV-RNA)– Baseline and routine monitoring q 3-6 months

– VL should be assessed 2-8 wks following initiation

• Genotypic Resistance Testing– All treatment-naïve patients entering care

– Prior to initiating therapy

– Suspected virologic failure

• Coreceptor Tropism Assay– Prior to initiation of a CCR5 antagonist

– Consider if failing CCR5 antagonist

• HLA-B*5701 Testing– Prior to initiation of abacavir therapy

When to Start HIV Treatment

56

When to Start: 2016 DHHS Guidelines

CD4+ Cell Count Recommendation

< 350 cells/mm³ Start ART (AI)

350-500 cells/mm³ Start ART (AI)

> 500 cells/mm³ Start ART (AI)

ART is also recommended for HIV-infected individuals for the prevention of transmission of

HIV

Perinatal transmission (AI)

Heterosexual transmission (AI)

Other transmission groups (AIII)

*Patients starting ART should be willing and able to commit to treatment and understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.

DHHS HIV Treatment Guidelines

Rating of Recommendations: A = Strong; B = Moderate; C = OptionalRating of Evidence: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = expert opinion

ART is recommended for all HIV-infected individuals to reduce the risk of disease progression.

DHHS Jan 2016: Tx-NaiveRecommended Regimens to Start

For All Pts, Regardless of

BL VL or CD4+ Count

INSTI

DTG/ABC/3TC*a

DTG + TDF/FTCa

EVG/cobi/TDF/FTCa (CrCl > 70 ml/min)

EVG/cobi/TAF/FTCa (CrCl > 30 ml/min)

RAL + TDF/FTCa

Boosted PI DRV/rtv + TDF/FTCa

*Only for pts who are HLA-B*5701 negative. a: 3TC may substitute for FTC or vice versa


DHHS Jan 2016: Tx-NaiveAlternative Regimens to Start

NNRTI EFV/TDF/FTCa

RPV/TDF/FTCa,b

Boosted PI

ATV/cobi + TDF/FTCa (CrCl > 70)

ATV/rtv + TDF/FTCa

(DRV/rtv or DRV/cobi) + ABC/3TC*a

DRV/cobi + TDF/FTCa,b (CrCl > 70)

*Only for pts who are HLA-B*5701 negative.

a: 3TC may substitute for FTC or vice versa

b: Only for patients with pre-treatment VL <100,000 copies/ml and CD4 count >200 cells/mm3


Regimens that are effective and tolerable, but that have potential disadvantages when compared with the recommended regimens listed above, have, or have less supporting data from randomized clinical trials. An alternative regimen may be the preferred regimen for some patients.


DHHS Jan 2016: Tx-Naive“Other Regimens” to Start

DHHS Jan 2016: ART Considerations for Tx

61DHHS HIV Treatment Guidelines


63


64

65


Antiretroviral Therapy Safety During Pregnancy

Class FDA Category

B C D

NRTIs ddIFTCTDF

ABC3TC d4TZDV

NNRTIs ETRNVPRPV

EFV

PIs ATVNFVRTVSQV

DRVFPVIDV

LPV/RTVTPV

Entry inhibitors ENFMVC

Integrase inhibitor RAL

68

Adherence Interventions

• Establish pt readiness to start therapy

• Provide education on medication dosing

• Review potential side effects

• Anticipate and treat side effects

• Utilize educational aids including pictures, pillboxes, and calendars

• Engage family and friends

• Simplify regimens, dosing, food issues

• Utilize team approach with nurses, pharmacists, and peer counselors

• Provide accessible, trusting health care team

Treatment Goal

DHHS Guidelines- Jan 2016

70

Treatment Regimen Failure: Causes

• Patient Factors

• Suboptimal adherence

• Antiretroviral side effects (intolerance)

• Alteration of antiretroviral pharmacokinetics

• ART resistance

• Inadequate potency of HAART

71

Treatment Regimen Failure

• Virologic Failure

– Inability to achieve/maintain an HIV-RNA < 200 copies/ml

• Immunologic Failure

– Failure to achieve and maintain adequate CD4 increase despite virologic suppression

• Clinical Failure

– Occurrence of HIV related events (after > 3 months of therapy)

72

Treatment-Experienced Patients: Virologic Failure

• Assess drug resistance:

– Drug resistance test

– Prior treatment history

– Prior resistance test results

• Drug resistance usually is cumulative –consider all previous treatment history and test results

Treatment-Experienced Patients: Management of Virologic Failure

• New regimen should contain at least 2 (preferably 3) fully active agents – Based on ARV history, resistance testing, and/or novel

mechanism of action

• In general, 1 active drug should not be added to a failing regimen(drug resistance is likely to develop quickly)

• Consult with experts

November 2015 www.aidsetc.org73

74

Pharmacist Interventions to Assist HIV Providers

• Assess appropriateness of all ART prescriptions with respect to appropriateness of combinations and doses

• Screen and alert providers for clinically significant drug interactions

• Assess appropriateness of opportunistic infection prophylaxis regimens

• Alert providers of adverse drug reactions and appropriately document/report such reactions

• Serve as a drug information expert

75

Pharmacist Interventions to Assist Patients

• Educate the public regarding risk factors for HIV transmission

• Appropriately counsel patients regarding their HIV and opportunistic infection drug regimens

• Provide patient with tools to maximize adherence

• Assist patients in preparing for and managing adverse effects of their medications

• Emphasize importance of receiving appropriate vaccinations

• Serve as a drug information expert

Select HIV-related Resources for the Pharmacist

• DHHS guidelines/resources– Website: http://aidsinfo.nih.gov

• New York State Department of Health AIDS Institute– Website: http://www.hivguidelines.org/

• Clinical Education Initiative– Website: http://www.ceitraining.org/

– CEI Line: 1-866-637-2342

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http://www.ceitraining.org/

QUESTIONS?

To set up training on HIV or Hepatitis C, please contact Naomi Harris at [email protected]

www.ceitraining.org

mailto:[email protected]

2016 hiv t u · 2018-04-01 · 2016 hiv treatment update john m. conry, pharm.d., aahivp, fnap...

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