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HIV/AIDS Treatment – Pharmacists Can Make a Difference

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HIV/AIDS Treatment- Pharmacists can

make a Difference

A Patient Centered Approach to HIV

for Pharmacists & Techs

Peter A. Kreckel

Adjunct Assistant Professor of Pharmacology

Department of Physician Assistant Sciences

St Francis University

PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing

pharmacy education

Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support

educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all

information and data before treating patients or employing any therapies described in this educational activity.

This program has been

supported by an educational

grant from Boehringer-Ingelheim

HIV/AIDS Treatment- Pharmacists can make a Difference

A Patient Centered Approach to HIV for Pharmacists & Techs

Accreditation:

Pharmacists: 0798-0000-10-062-L02-P

Pharmacy Technicians: 0798-0000-10-062-L02-T

CE Credits: 1 contact hour

Target Audience: Pharmacists & Technicians

Program Overview:

Pharmacists can make a difference in the management and treatment of HIV/AIDS. However, many pharmacists find

themselves uncomfortable with their level of knowledge in the area of HIV either because they did not receive any HIV

training in their formal education or simply because of the rapid on-going advancements in this therapeutic area. This

program will educate pharmacists and pharmacy technicians on HIV treatment principles, provide an update on

pharmacotherapy, and the challenges associated with HIV treatment so they can more comfortable respond to HIV patients

and providers in their role as pharmacist and technician.

Objectives:

• Describe the primary goals of antiretroviral (ARV) treatment and the rationale for prescribing combination therapy.

• Provide an update on antiretroviral therapy (ARV) for HIV to include their mechanisms of action, efficacy, dosing, safety and

tolerability profiles.

• Recognize possible drug interactions between different antiretrovirals and interactions between antiretrovirals and other

medications.

• Describe the pharmacist’s critical role in counseling and educating HIV patients on drug treatment strategies to improve the

patient outcomes and medication adherence.




HIV/AIDS Treatment- Pharmacists can make a Difference

A Patient Centered Approach to HIV for Pharmacists & Techs

PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing

pharmacy education

Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies

that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed.

Participants should verify all information and data before treating patients or employing any therapies described in this educational activity.




Speaker: Peter A. Kreckel R.Ph. is a graduate of the University of Pittsburgh, Bachelor of Science in Pharmacy, Magna

Cum Laude, Class of 1981. He served as the President of the Pharmacy School Class of 1981 for 3 years, and President

of the Pharmacy School Student Council for 2 years. During this time he received the Upjohn Achievement Award for

leadership and academic achievement. In addition to managing a retail pharmacy, pharmacist Kreckel is an Adjunct

Assistant Professor of Pharmacology, Department of Physicians Assistant Sciences, St. Francis University. His

assignments include teaching a HIV pharmacotherapy course for Physician Assistant students, currently doing their

clinical rotations, that are pursuing a Masters of Medical Science Degree from St. Francis University.

Speaker Disclosure: Mr. Kreckel has no actual or potential conflicts of interest in relation to this program.

GOALS of HIV DRUG THERAPY

GOAL: to extend life and the quality of life

1981- 1991: only 44% were living after

diagnosis.

1996-2000: 85% of patients were living after

diagnosis




Primary Goals of ARV therapy

CD4 count: 700-1000/mm3 (about a pea-size drop of blood)

CD4 cells are a type of lymphocyte (white blood cell). They are an important part of the immune system. CD4 cells are sometimes called T-cells. T-4 cells, also called CD4+, are “helper” cells. They lead the attack against infections.

Patients need this count to be HIGH

Some clinicians use CD4% normal range:20-40%. Less than 14% shows significant immune damage.

Suppress HIV levels (viral load) below the limit of detection (<50 copies HIV RNA), or as low as possible for as long as possible

HAART therapy can be compared to a Canoe approaching a

waterfall! The canoeists are paddling upstream to avoid the

waterfalls.

CD4 count= the distance to the falls (the longer the better)

Viral load = the speed of the river (the lower the better)

HAART therapy= the stronger the paddlers the longer until you go over the falls.




CD4 Levels and opportunistic

infections

Most health care providers prescribe drugs to prevent opportunistic infections at the following CD4 levels:

Less than 200: pneumocystis pneumonia (PCP)

Less than 100: toxoplasmosis

Less than 50: mycobacterium avium complex (MAC)

Because they are such an important indicator of the strength of the immune system, official treatment guideline in the US suggest that CD4 counts be monitored every 3 to 4 months.

Treatment and prevention of

Opportunistic Infections

Disease Primary

Treatment

Prophylaxis

Pneumocystis

jiroveci (PCP)

CD4<200

Trimeth/Sulfa-DS

(2) q8h x21 days

Trimeth/SulfaDS

daily or 3 x week.

Dapsone 100mg qd

Toxoplasmosis

CD4<100

Pyramethamine +

sulfadiazine

Trimeth/Sulfa DS

q24hr.

Mycobacterium

avium (MAC)

CD4<50

Clarithro 500 q12

Azithro 600 qd +

ethambutol

CLAR 500q12h Azith

1200/week

Tuberculosis INH + RIF+PZA

(adjust if on PI)

INH-300 q24 +

pyridoxine

When to Start HAART????

HIV

symptoms?

CD4 count Start

Treatment?

Comments

Yes Any Yes ANY AIDS defining

illness, start treatment.

No <200 Yes

No 200-

350

Yes* New DHHS

recommendation

No 350< No** Maybe if CD4 decreasing rapidly

or viral load >100,000 copies/ml

When the CD4 count goes below 350, most

health care providers begin HAART

Should we wait to start HAART?

HIV-related morbidity and mortality derive not only from immune deficiency but also from direct effects of HIV on specific end organs and the indirect effects of HIV-associated inflammation on these organs. In general, the available data demonstrate that:

Untreated HIV infection may have detrimental effects at all stages of infection.

Treatment is beneficial even when initiated later in infection. However, later therapy may not repair damage associated with viral replication during early stages of infection.

Earlier treatment may prevent the damage associated with HIV replication during early stages of infection.

Maximal viral suppression-less likely transmission

THE simple answer: NO! Don’t wait

http://www.hubtesting.net/yahoo_site_admin/assets/images/bacteria.94120838_std.jpg

http://www.pillidentifier.net/img/upload/pill_bottle_and_pills.jpg




Successful HAART Therapy

Cocktails?? The rationale for Combo therapy

Need to have at 3 active drugs from

MULTIPLE drug classes.

When maximal suppression is NOT

achieved or LOST changing to a new

regimen with at least two active drugs is

required.

NEVER change only 1 drug in a

failing regimen.

AIDS DEFINING

CONDITIONS A-I

Candidiasis of bronchi, trachea, or lungs

Candidiasis, esophageal

Cervical cancer, invasive

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (greater than 1 month's duration)

Cytomegalovirus disease (other than liver, spleen, or nodes)

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy, HIV-related

Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (>1 month's duration)

AIDS DEFINING

CONDITIONS K-W Kaposi's sarcoma

Lymphoma, Burkitt's (or equivalent term)

Lymphoma, immunoblastic (or equivalent term)

Lymphoma, primary, of brain

Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary

Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary

Pneumocystis carinii pneumonia

Pneumonia, recurrent

Progressive multifocal leukoencephalopathy

Salmonella septicemia, recurrent

Toxoplasmosis of brain

Wasting syndrome due to HIV




1)Fusion and

entry

2)Reverse

transcript-

ase

3)Integrase

4)Protease

LIFECYCLE of HIVMechanism Overview of HIV Therapy

Keep virus from attaching to CD-4 cell

Fusion inhibitor (Fuzeon®- enfurvirtide)

Keep virus from entering CD4 Cell

Entry inhibitor (Selzentry®-maraviroc)

Inactivate the BIG 3 enzymes

Reverse Transcriptase

NRTI (7 available) & NNRTI (4 available)

Integrase

Integrase inhibitor (Isentress®- raltegravir)

Protease

Protease inhibitor (9 available)

HAART Therapy- The Drug classes

5 mechanism of actions

6 different drug classes

Fusion Inhibitor

Entry Inhibitor

Nucleoside/Nucleotide Reverse Transcriptase inhibitor (NRTI)

Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)

Protease Inhibitor (PI)

Integrase Strand Inhibitor (INSTI)

Basic Regimens: Advantages:

NRTI: “backbone therapy”. Minimal drug

interactions.

NNRTI: preserving PI for future use. Long half

life. Less metabolic toxicity than PI’s

PI: very potent. High genetic barrier to

resistance.

INSTI: may take with food, minimal drug

interactions. Well tolerated.




Basic Regimens: Disadvantages

NRTI: Lactic acidosis and hepatic steatosis reported with most NRTIs (rare)

NNRTI: Low genetic barrier to resistance. P450 inducers. Cross resistance. Rash. Hepatotoxicity

PI: lots of drug interactions. P450 blockers. GI intolerance. Metabolic complications.

INSTI: headache, diarrhea, nausea, muscle pain, CK elevation. BID dose

INTERACTIVE QUESTION

What is the expected durability of an HIV regimen, when the patient is compliant?

a) 6 months-3 years

b) 3-6 years

c) 6-10 years

TYPE your

answer in

the CHAT

BOX now!

Durability of HIV regimen

With the efavirenz based or PI based

regimens, and GOOD adherence patients are

seeing viral regimens lasting 10 years. Eight

years is the average. ANSWER-C

With even newer potent PI’s and integrase

strand inhibitors, this number could very well

increase

With good adherence HIV can be considered

a manageable chronic disease

Drug Interactions with

anti-Retroviral Drugs

Increases in serum drug levels caused by inhibitors of

metabolism may increase risk of medication toxicity,

while decreases in drug levels caused by inducers of

metabolism may cause treatment failure

Some drug interactions may be exploited, eg, low-dose

ritonavir (a strong CYP3A4 inhibitor) may be used as a

pharmacokinetic enhancer to increase concentrations

and prolong the half-life of other PIs

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Review of Cytochrome P450

Responsible for the metabolism of numerous drugs

Statins (HMGcoA

reductase inhibitors)

Simvastatin (Zocor®), Lovastatin (Mevacor), Atorvastatin

(Lipitor) are extensively metabolized by P450-3A4

Anti epileptic

medications

Phenytoin (Dilantin®), Carbamazepine (Tegretol®),

Phenobarbital

Antibiotics Erythromycin (E-mycin®), Clarithromycin (Biaxin®)

Telithromycin (Ketek®)

Antidepressants Fluoxetine (Prozac®), Sertraline (Zoloft®), Citalopram

(Celexa®), Paroxetine (Paxil®)

Methadone

Azole antifungals Ketoconazole (nizoral®), Fluconazole (Diflucan)

Amiodarone (Cordarone®)

Protease Inhibitors

RITONAVIR BOOSTING “the ultimate beneficial drug-drug interaction”

Ritonavir (Norvir®) by Abbott Labs

(available at capsules or tablets)

Is the most potent inhibitor of the Cytochrome P450 enzyme system

ALL PI are substrates of CYP450-3A4 so their metabolic rate may be

altered in the presence of CYP inducers or inhibitors

Consultation with HIV patients

“Communication skills are essential in any

patient consultation scenario. That being

said, product knowledge is paramount before

any discussion of ANY drug therapy with ANY

patient”

Peter Kreckel- shares this with any pharmacy student.

Viral Fusion Inhibitor(used for treatment experienced patients—salvage therapy)

Mechanism:

Blocks the fusion of the HIV virus into the host cell

Adverse reactions:

Injection site reactions, recurrent pneumonia, diarrhea,

nausea, fatigue

Fuzeon ® Enfuviritide T-20 dose 90mg SQ BID 60 = $2,552.74

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CCR5 Co-Receptor Antagonist(used for treatment experienced patients)

Mechanism: Binds to a receptor called CCR5 on white

blood cells.

Adverse reactions: hepatotoxicity, cough, pyrexia, upper respiratory infections, abdominal pain, dizziness

Selzentry® maraviroc 300mg BID

(adjust for P450)

$900.00/ month

Brand Generic Abbr Dosage

Emtriva® Emtricitabine FTC 200mg daily

Epivir® Lamivudine 3TC 150mg BID or 300/day

Retrovir® Zidovudine AZT 300mg BID

Videx® Didanosine ddl 250mg or 400mg daily

Viread® Tenofovir DF TDF 300mg/day

Zerit® Stavudine d4T 20, 30 or 40mg BID

Ziagen® Abacabir ABC 300mg BID or 600mg/day

Videx EC ® didanosine 250-400mg daily

NRTI (nucleoside/nucleotide reverse transcriptase inhibitors)

Mechanism: NRTI interfere with viral-RNA dependent DNA-polymerase resulting in chain termination and inhibition of viral replication.

Use 2 drugs from this class for “backbone therapy”)

NOTE: Preferred combo: tenofovir + emtricitabine

for all 4 regimens for treatment naïve patients

NNRTI- non-nucleoside reverse transcriptase

inhibitors.

Brand Generic Abbr Dosage

Viramune® Nevirapine NVP 200mg daily x14 days, then

200q12

Sustiva® Efavirenz EFZ 600mg HS

Rescriptor® Delaviridine DLV 400-600 mg every 8 hours

Intelence® Etravirine 200mg (2x100mg) BID pc

NNRTI preferred agents:

Sustiva is NNRTI of choice unless pregnant- Preg cat-D

Viramune is NNRTI of choice if pregnant.

Sustiva+ Truvada= Atripla one pill daily.

highly selective, noncompetitive inhibitors of HIV-1 reverse

transcriptase. Class cross resistance (except Intelence)

Integrase Inhibitors

Mechanism: Interferes with enzyme needed to integrate

viral DNA into host cell DNA. It transports the proviral

DNA into the host cell nucleus. There it is integrated

into the target cells' DNA.

Adverse reactions: headache, nausea,

diarrhea, pyrexia, CK elevation,

rhabdomyolysis, myopathy.

Isentress® Raltegravir 400mg BID + or -

food

60 = $1072.24

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Protease Inhibitors:

Mechanism: reversible inhibitors of HIV

aspartyl protease, a viral enzyme responsible

for the cleavage of the viral polyprotein into a

number of essential enzymes and several

structural proteins.

Adverse reactions: Lipodystrophy,

hyperglycemia, lipid metabolism,

osteonecrosis, osteopenia, osteoporosis,

Protease Inhibitors

Brand Generic Abbr DosageViracept® Nelfinavir NFV 1250mg q12

Norvir® Ritonavir RTV 100-400mg with other PI for intensification

Crixivan® Indinavir IDV 800mg q 8 hrs

Agenerase® Amprenavir APV 1200mg q 12hr

Invirase® Saquinavir (hard

gelcap)

SQV-

HGC

400mg q12 with 400mg Ritonavir

Reyataz® Atazanavir TAZ 400mg daily

Kaletra® Lopinavir

/Ritonavir

LPV/r 200mg/50mg BID

Aptivus ® Tipranavir 500mg BID give with ritonivir

Lexiva® fosamprenivir 1.4gm BID

Preferred drugs:

•Reyataz boosted with ritonavir

•Prezista boosted with ritonavir (avoid acid suppression)

Preferred Regimens December 1, 2009 Guidelines for the Use of Antiretroviral Agents in HIV

Infected Adults and Adolescents. Page ii

4 regimens are now listed as “Preferred regimens” for treatment- naïve patients:

1. efavirenz/tenofovir/emtricitabine (Atripla)

2. ritonavir-boosted atazanavir + tenofovir/emtricitabine (Norvir/Reyataz+Truvada)

3. ritonavir-boosted darunavir + tenofovir/emtricitabine (Norvir/Prezista+Truvada)

4. raltegravir + tenofovir/emtricitabine (Isentress+Truvada)

The Pharmacist’s Role in HIV care

The American Society of Health System Pharmacists

(ASHP) believes that pharmacists have a role in the

care of patients infected with human

immunodeficiency virus (HIV).

Pharmaceutical care is the direct, responsible

provision of medication-related care for the purpose

of achieving definite outcomes that improve a

patient’s quality of life.

Developed through the ASHP Council on Professional Affairs. Approved by the ASHP

Board of Directors on April 15, 2003, and by the ASHP House of Delegates on June 1,

2003. This statement was reviewed in 2008 by the Council on Pharmacy Practice and

by the Board of Directors and was found to still be appropriate.




What about Vaccines?

In general we avoid live vaccines in HIV patients.

Severe varicella may occur in un-immunized children. Consider vaccine if over 12 months, and CD4 percentage is 15% or greater.

May give MMR if asymptomatic HIV, if CD4% is 15% or over if age 13 or less. May give MMR if CD4% is 14% and over 13 yrs old.

Don’t give Zoster vaccine if symptomatic

Don’t give intranasal vaccine to any HIV pt.

THE PHARMACIST’S ROLE

Providing product, inventory management

Learn more about HIV medications and

therapy

Monitor for adherence

Provide dose monitoring devices

Appropriate References:

Sanford Guide to HIV/AIDS therapy

www.aidsinfo.nih.gov

hivinsite.ucsf.edu

Adherence and CD4 response

Level of

Adherence

Change in

CD4 count

>95% +60

80-95% +54

<80% -13

Adherence level

•95% is missing 1 dose

a month or less.

•80% would be missing

6 doses per month

Predictors of Inadequate Adherence

Regimen complexity and pill burden

Low literacy level

Active drug use or alcoholism

Stigma

Mental illness (especially depression)

Cognitive impairment

Lack of patient education

Medication adverse effects

Treatment fatigue




Predictors of Inadequate Adherence (2)

Age, race, sex, educational level, socioeconomic

status, and a past history of alcoholism or drug use

do NOT reliably predict suboptimal adherence

Higher socioeconomic status and education levels

and lack of history of drug use do NOT reliably

predict optimal adherence

Pill Box Reminders

Use of a pillbox increased adherence to HIV

therapy by more than 4%

Use of pillbox increased the probability of

achieving a viral load of less than 400

copies/ml by 15%

Source: APhA DrugInfoLine (Oct-2007)

HIV patient profile “RF”NNRTI based regimen

DRUG CoPAY

Crestor 20mg 6.00

Ziagen 300mg 0.00

Diovan/HCT 80 0.00

Glimeperide 0.00

Chlordiazepoxide-10 17.98

Mirtazapine 15mg 0.00

Propox/APAP 100/650 0.00

Hydrocod/APAP 7.5/500 0.00

Epivir 150mg 0.00

Sustiva 600mg 0.00

Niaspan 1000mg 6.00

Profile of Female patient “ML”(INSTI based regimen)

Clonazepam 0.5mg One HS

Lovaza 2 caps BID

Citracal-D

Alendronate 70mg

8 tablets daily-divided dose

Once a week

Boost energy drink 1 unit TID

Nexium 40mg 1 each am

Isentress 400 2 tablets daily

Truvada 1 tablet daily

Gabapentin 300mg 3 capsules HS




Profile of BT

Ibuprofen 800 1 tablet 3 times daily

Dapsone 100mg 1 tablet daily (pcp)

Emtriva 200 (D/C) 1 capsule daily

Sustiva 600mg (D/C) 1 hs –empty stomach

Viread 300 (D/C) 1 tablet daily

Truvada 1 tablet daily

Isentress 2 tablets daily

Proair inhaler 2 puffs up to 4 times daily

Notes

Notes Notes

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