hiv 101: basics of hiv patient care · strengthen • advocate • promote hiv is a virus from the...
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Strengthen • Advocate • Promote
Rich DeBenedetto, PharmD, MS, AAHIVP
1
HIV 101:
Basics of HIV Patient Care
Strengthen • Advocate • Promote
Identify complete HIV therapeutic regimens
Describe several common drug interactions with HIV therapy
Discuss pharmacy related problems in HIV care
Objectives
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HIV is a virus from the genus Lentivirus of the family Retroviridae
The family clues us into the fact that HIV is a retrovirus
Lentivirus is a genus of immunodeficiency viruses which are able to infect and deliver viral RNA into CD4,
T-helper cells
HIV is transmitted through blood, sexual contacts, and perinatally
HIV was first identified in 1981 in MMWR identifying rare pneumonia cases in 5 previously healthy young
men.
Throughout the 1980’s there was a huge stigma placed upon HIV being a disease for gay men and users of IV
drugs. So much so that President Regan was not found mentioning HIV publicly until 1987.
Today HIV affects all people, regardless of race, sexual orientation, and drug use status.
HIV description
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Anderson PL, Kakuda TN, Fletcher CV. Chapter 103. Human Immunodeficiency Virus Infection. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey
L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811495. Accessed December 06, 2016.
CDC. Pneumocystis Pneumonia – Los Angeles. MMWR 1981;30(21);1-3.
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Virus enters cell and uncoats
Reverse transcription (no proofreading!!)
Single stranded RNA →
DNA/RNA complex →
Double stranded viral DNA
Viral DNA is integrated into the cellular DNA
Viral mRNA and vRNA is transcribed using human
mechanisms
Viral proteins are translated using human
mechanisms
Viral proteins are cut into the correct size and shape
by protease
Retrovirus replication
4 http://www.mhhe.com/socscience/sex/common/ibank/ibank/0143.jpg
Flexner C. Antiretroviral Agents and Treatment of HIV Infection. In: Brunton LL, Chabner BA, Knollmann BC. eds.
Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e. New York, NY: McGraw-Hill; 2011.
http://accesspharmacy.mhmedical.com/content.aspx?bookid=1613&Sectionid=102163791. Accessed December
05, 2016.
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Entry Inhibitors
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Integrase Inhibitors
Protease Inhibitors (PIs)
Pharmacokinetic Enhancers (boosters)
Medication classes
5DHHS HIV Guidelines 7/2016
https://www.poz.com/drug_charts/hiv-drug-chart
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Nucleoside Reverse Transcriptase Inhibitor Drugs
Tenofovir (TDF) - Viread
Tenofovir (TAF) - not available alone
Emtricitabine - Emtriva
Lamivudine - Epivir
Abacavir - Ziagen
Didanosine - Videx
Stavudine - Zerit
Zidovudine - Retrovir
NRTIs (Nukes)
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NRTI Combination Products
Truvada (tenofovir DF /emtricitabine)
Descovy (tenofovir AF /emtricitabine)
Epzicom (lamivudine /abacavir)
Trizivir (lamivudine/zidovudine/abacavir)
Combivir (lamivudine/zidovudine)
https://www.poz.com/drug_charts/hiv-drug-chart
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Non Nucleoside Reverse Transcriptase Drugs
Efavirenz - Sustiva
Rilpivirine - Edurant
Etravirine - Intelence
Nevirapine - Viramune
Delavirdine - Rescriptor
NNRTI
7 https://www.poz.com/drug_charts/hiv-drug-chart
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Dolutegravir - Tivicay
Elvitegravir - Vitekta
Raltegravir - Isentress
Integrase Inhibitor
8 https://www.poz.com/drug_charts/hiv-drug-chart
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PI Drugs
Darunavir - Prezista
Atazanavir - Reyataz
Lopinavir - not available alone
Nelfinavir - Viracept
Fosamprenavir - Lexiva
Tipranavir - Aprivus
Indinavir - Crixivan
Saquinavir - Invirase
Protease Inhibitor
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PI Combination Products
Prezcobix - Darunavir / Cobicistat
Evotaz - Atazanavir / Cobicistat
Kaletra - Lopinavir / Ritonavir
https://www.poz.com/drug_charts/hiv-drug-chart
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Miraviroc - Selzentry
Enfuvirtide - Fuzeon
Entry Inhibitor
10 https://www.poz.com/drug_charts/hiv-drug-chart
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Ritonavir - Norvir
Cobicistat - Tybost
Pharmacokinetic Enhancers
11 https://www.poz.com/drug_charts/hiv-drug-chart
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Genvoya (Elvitegravir/Cobicistat/Tenofovir AF/Emtricitabine)
Stribild (Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine)
Triumeq (Dolutegravir/Abacavir/Lamivudine)
Odesfey (Rilpivirine/Tenofovir AF/Emtricitabine)
Complera (Rilpivirine/Tenofovir DF/Emtricitabine)
Atripla (Efavirenz/Tenofovir DF/Emtricitabine)
Single Tablet Regimens
12 https://www.poz.com/drug_charts/hiv-drug-chart
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Currently available HIV medications
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Nucleoside/tide Reverse Transcriptase Inhibitors (NRTIs)
•Abacavir (ABC)
•Didanosine (ddI)
•Emtricitabine (FTC)
•Lamivudine (3TC)
•Stavudine (D4T)
•Tenofovir (TDF)
•Tenofovir (TAF)
•Zidovudine (ZDV)
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
•Delavirdine (DLV)
•Efavirenz (EFV)
•Etravirine (ETR)
•Nevirapine (NVP)
•Rilpivirine (RPV)
Single tablet regimens
Tenofovir + emtricitabine + efavirenz (Atripla®)
Elvitegravir + cobicistat + emtricitabine + tenofovir
(TDF)(Stribild®)
Elvitegravir + cobicistat + emtricitabine + tenofovir
(TAF)(Genvoya®)
Dolutegravir + abacavir + lamivudine (Triumeq®)
Tenofovir (TDF) + emtricitabine + rilpivrine (Complera®)
Tenofovir (TAF) + emtricitabine + rilpivrine (Odefsey®)
Portions of therapy
Tenofovir + emtricitabine (Truvada®)
Lamivudine + abacavir (Epzicom®)
Atazanavir + cobicistat (EvoTaz®)*
Darunavir + cobicistat (Prezcobix®)*
Lopinavir +ritonavir (Kaletra®)
Zidovudine + lamivudine + abacavir (Trizivir®)
Zidovudine + lamivudine (Combivir®)
Protease Inhibitors (PIs)•Atazanavir (ATV/r)
•Darunavir (DRV/r)
•Fosamprenavir (FPV)
•Indinavir (IDV)
•Lopinavir/Ritonavir (LPV/r)
•Nelfinavir (NFV)
•Ritonavir (RTV)
•Saquinavir (SQV)
•Tipranavir (TPV)
Integrase Inhibitor•Elvitegravir (EVG)
•Dolutegravir (DTG)
•Raltegravir (RAL)
Fusion Inhibitors•Enfuvertide (T-20)
CCR5 Antagonist•Maraviroc (MVC)
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Truvada has which components?
What class(es) of medication is Truvada?
Renal toxicity is associated with which medication?
Genvoya has which components?
HLA hypersensitivity reaction is associated with which medication?
Triumeq has which components?
Darunavir is which class of medication?
Knowledge quiz
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Highly Active Anti-Retroviral Therapy (HAART)
A drug cocktail which works to suppress HIV via 3 active HIV therapies from 2 classes of medication.
Decreases ability of virus to reproduce and mutate.
Lowers the amount of medication required to suppress the virus.
Backbone of 2 NRTIs and ‘something else’
Eg. Truvada (tenofovir DF/emtricitabine) + Tivicay (dolutegravir)
2 NRTIs + NNRTI, Boosted PI, or Integrase Inhibitor
Complete Therapy
15DHHS HIV Guidelines 7/2016
https://www.aids.gov/hiv-aids-basics/hiv-aids-101/aids-timeline/
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Which of the following is a complete regimen?
Truvada + Prezcobix
Emtricitabine + Abacavir + Tenofovir
Lamivudine + Abacavir + Dolutegravir
Darunavir + Ritonavir + Atazanavir
Elvitegravir + Cobicistat + Emtricitabine + Tenofovir AF
Efavirenz + Rilpivirine + Lamivudine
Descovy
Triumeq
Application quiz
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The HIV virus contains 9749 base pairs and has an error rate of a mutation every 5000-10,000 base pairs
1-2 mutations every time the genome is reverse transcribed
The replication cycle time is about 1-2 days – about 200-300 generations each year
Resistance can build to medications when exposure is not at appropriate concentrations due to non-adherence or
other issues
Resistance to one medication may confer class resistance
Resistance cannot form without viral replication
Resistance
17http://uhavax.hartford.edu/bugl/hiv.htm
Coffin J, Swanstrom R. Cold Spring Harb Perspect Med 2013; 3.
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Cytochrome P-450
Protease Inhibitors -3A4 inhibitor
Cobicistat -3A4 inhibitor
Efavirenz -3A4 substrate
Antacids / Polyvalent cations
Effect the absorption of Integrase Inhibitors
Rilpivirene and Atazanavir affected by high pH
Food
Some products require dosing based on food
presence or absence
Interactions
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Inhibition of CYP enzymes can prevent metabolism and raise levels
of other drugs
Statins can increase to extreme concentrations (simva ↑
3000%)
Cardiovascular medications can increase to higher levels
Opiate levels may be increased (PIs are used in maintaining
longer highs)
Benzodiazepine levels may be increased
↓Integrase inhibitor concentration can reduce the efficacy and
allow for mutations and resistance to build
Some products require presence or absence of food for absorption
to achieve appropriate levels for efficacy
Some products require presence or absence of food to prevent
adverse effects
Liverpool drug interactions http://www.hiv-druginteractions.org/treatment_selectors Accessed 10/1/16
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Evelyn is a 52 year old WF who takes Simvastatin 40mg, Metformin 500mg, and a multivitamin, brings in a prescription for Prescobix
and Descovy. Is this going to be an acceptable regimen for her, why or why not?
No, Simvastatin concentration could be increased by well over 1000% - toxicity
Rachel is a 34 year old AAF who brings in a prescription for Genvoya, Centrum Daily, enalapril, and you know she also takes occasional
Maalox from previous recommendations you’ve given her. Is this going to be an acceptable regimen for her, why or why not?
Multivitamin or antacid with Genvoya may decrease Elvitegravir – Drugs need to be separated INSTI 2 hours before or 6 hours
after multivitamin and separated by 4 hours from Maalox
Kirby, a 42 year old AAM, brings in a pile of prescriptions for Triumeq, Lisinopril 20mg, Prilosec 20mg, Claritin 10mg, and Valacyclovir
1g. Is this an acceptable medication regimen, why or why not?
– only if HLA neg
Frank brings in prescriptions with: Viread every Monday, Lamivudine 100mg ¼ tablet every day, and Tivicay 1 tablet daily. He also has
on his profile Lexapro 10mg, amlodipine 5mg, bumetanide 2mg, and Lipitor 40mg. Is this an acceptable regimen?
Only if you know why the meds are being dosed so strange… this would be a good dosage range for someone in kidney failure,
otherwise levels would not suppress and lead to resistance.
Synthesis Quiz
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IT IS BETTER TO NOT TAKE ANY MEDICINE THAN TO TAKE A PARTIAL REGIMEN
Patients should only receive complete therapy regimens
If not check where their other meds are coming from and that they are being dispensed
Do not out of stock portions of therapy or dispense partials
Check previous regimen
Make sure you are dispensing what they had previously filled, if not question why
Call on drug interactions and questions, you may have a more complete medication list than the prescriber,
interactions matter
“Dispense in original container”
Dispensing HIV Medications
20 Guide for HIV/AIDS Clinical Care – 2014 Edition
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Medication adherence is strongly correlated with viral suppression, reduced resistance, and increased survival
Identify barriers to adherence before starting ART
Assess adherence at every opportunity and provide reminder education on adherence importance
Good methods to help adherence include
Pill boxes, Pill packs/bags
Tying medication taking to specific regular activities (meal, brushing teeth, at bed, Jeopardy) and having
medications available in that area
Adherence support in the home
Alarms – if this is recommended, ask them to do it in front of you “so they don’t forget”
Discussing reason why patient wants to take medications
Have patient identify times when dosage was missed, problem that was encountered and solutions to that issue
Medication too large – Pill Glide, smaller tablets, liquid, or chewable formulations
Forgot to pack on an overnight – Reminder note in overnight bag or luggage
Adherence/Med Timing/Support
21Rudy JB, et.al. AIDS Patient Care STDS. 2009 Mar; 23(3): 185–194.
Guide for HIV/AIDS Clinical Care – 2014 Edition
Strengthen • Advocate • Promote
Anderson PL, Kakuda TN, Fletcher CV. Chapter 103. Human Immunodeficiency Virus Infection. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic
Approach, 9e. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811495. Accessed December 06, 2016.
CDC. Pneumocystis Pneumonia – Los Angeles. MMWR 1981;30(21);1-3.
Flexner C. Antiretroviral Agents and Treatment of HIV Infection. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e. New York, NY:
McGraw-Hill; 2011. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1613&Sectionid=102163791. Accessed December 05, 2016.
http://www.mhhe.com/socscience/sex/common/ibank/ibank/0143.jpg
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. Available at
http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 9/20/16
https://www.aids.gov/hiv-aids-basics/hiv-aids-101/aids-timeline/
https://www.poz.com/drug_charts/hiv-drug-chart
Liverpool drug interactions http://www.hiv-druginteractions.org/treatment_selectors Accessed 10/1/16
http://uhavax.hartford.edu/bugl/hiv.htm
Coffin J, Swanstrom R. HIV pathogenesis: dynamics and genetics of viral populations and infected cells. Cold Spring Harb Perspect Med 2013; 3.
U.S. Department of Health and Human Services, Health Resources and Services Administration, Guide for HIV/AIDS Clinical Care – 2014 Edition. Rockville, MD: U.S. Department of Health and Human
Services, 2014
Rudy JB, Murphy DA, Harris DR, et.al. Patient-Related Risks for Nonadherence to Antiretroviral Therapy among HIV-Infected Youth in the United States: A Study of Prevalence and Interactions. AIDS Patient
Care STDS. 2009 Mar; 23(3): 185–194.
References
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