Tools and Principles for Optimizing Adherence to HIV Regimens
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Transcript of Tools and Principles for Optimizing Adherence to HIV Regimens
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TOOLS AND PRINCIPLES FOR
OPTIMIZING ADHERENCE TO HIV REGIMENS
Edric Paw Cho Sing, Pharm. D. 2015 CandidateUniversity of Toronto Faculty of PharmacyAdvanced Pharmacy Practice Experience
Novack’s Rexall Drug Store
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PRESENTATION OVERVIEW• HIV/AIDS Today• HIV Drug Resistance• Mechanism of Drug Resistance• Impact of Adherence• Clinical Tools for Every Day Practice
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1 in 10 ART-naïve patients carried HIV with ≥1 drug resistance mutation.
Rates of drug resistant HIV in ART-naïve patients have been rising, from 3.4% during 1995-1998, to 12.4% by 1999-2000.
North America was found to have the highest prevalence of transmitted resistance (12.9%)
HIV/AIDS TODAY
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HIV RESISTANCEHIV replication is sloppy!
≥1 mutation per genome transcribed ~20 billion mutations/day
HIV replication is high volume!
~10 billion copies/day 107-108 infected cells/day
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HIV RESISTANCEHIV resistance can arise in 3 ways:
① Sloppy replication (infidelity)
② Through transmission (transmitted resistance)
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HIV RESISTANCEHIV resistance can arise in 3 ways:
① Sloppy replication (infidelity)
② Through transmission (transmitted resistance)
③ Selective pressures (acquired resistance)
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WHAT IS DRUG RESISTANCE?Drug Resistance – Ability of disease-causing microorganisms (e.g. bacteria or viruses) to continue multiplying despite the use of otherwise effective drugs.
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MOR: Excision of incorporated NRTI
“Thymidine Analogue Mutations”
MECHANISM OF DRUG RESISTANCE: NRTI
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MOR: Reduction of NNRTI affinity to allosteric site Drug-dependent mutations (K103N efavirenz,
Y181C nevirapine)
MECHANISM OF DRUG RESISTANCE: NNRTI
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MOR: Enlargement of catalytic site, reduction of PI affinity to the enzyme
MECHANISM OF DRUG RESISTANCE: PI
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MUTATIONS AND RESISTANCELow Genetic Barrier – Single mutations which cause complete resistance
Ex. All NNRTI, 3TC
High Genetic Barrier – Multiple step-wise mutations needed to cause resistance
Ex. Protease Inhibitors, most NRTI
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DISTRIBUTION OF DRUG RESISTANCEReduced susceptibility more common for NNRTI’s compared to NRTI’s or PI’s
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95% ADHERENCEIt is recommended that adherence be maintained above 95% to achieve optimal outcomes
Level of Adherence Once-Daily Regimen Twice-Daily Regimen
>95% Adherence No more than 1 dose per month
No more than 3 doses per month
>90% Adherence No more than 3 doses per month
No more than 6 doses per month
>80% Adherence No more than 1 dose per week
No more than 3 doses per week
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95% ADHERENCEExample #1: Once-daily regimen
FTC/TDF (Truvada)Raltegravir (Isentress)
FTC/TDF/ELV/c (Stribild)
Example #2: Twice-daily regimen
Miss no more than 1 dose per month
Miss no more than 3 doses per month
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THE BRITISH COLUMBIA STUDYObjective: To examine long-term effects of adherence on virologic and immunologic response
Primary Outcome: Immunologic response (CD4+): ≥145 cells/uL Virologic response (pVL+): 65% of the time with VL<50 copies/mL
Stratification of Responses: Best response (CD4+/pVL+) Incomplete response (CD4+/pVL- or CD4-/pVL+) Worst response (CD4-/pVL-)
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THE BRITISH COLUMBIA STUDYHighly adherent patients (>95%) achieved a median viral
load suppression 78.8% of the follow-up time.
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THE BRITISH COLUMBIA STUDYAfter adjustment for certain baseline characteristics,
the probability for “best” response was higher for highly adherent patients (>95%)
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THE BRITISH COLUMBIA STUDY
Worst response associated with higher mortality (OR 6.09), progression to AIDS/death (OR 3.25),
and emergence of drug resistance (OR 10.56) compared to best response
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THE BRITISH COLUMBIA STUDY
Conclusion: Adherence is a key feature influencing both virologic and
immunologic responses. When adherence < 95%, patients were more likely to experience
poor responses to treatment. When adherence > 95%, NNRTI and PI/r –based regimens
provided the highest likelihood of virologic and immunologic response.
Poor virologic and immunologic response led to negative health outcomes.
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ASSESSING ADHERENCE
1. Acknowledge the difficulties of adherence
“Taking pills every day is hard. Most people have problems taking their pills at some point during treatment. I am going to ask you about problems that you may have had taking your pills. Please feel comfortable telling me about pills you may have missed or taken late. I am asking because I want to make it easier for you to take them.”
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ASSESSING ADHERENCE
2. Confirm understanding of the regimen
• “How many of [Drug A] are you taking per day?”
• “How often do you take [Drug A] per day?”
• “Are there any special instructions that you follow?”
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ASSESSING ADHERENCE
3. Self-Assessment of Adherence
• Over the past 3 days
• Over the past week
• Over the past month
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ASSESSING ADHERENCE
4. Reasons for Missed Doses
• Forgetful
• Away from home
• Too busy
• Side effects
• Feeling sick or depressed
• Ran out of pills
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ASSESSING ADHERENCE
5. Ask about side effects or other problems
• “Do you have any difficulty swallowing the medications?”
• “Do the medications upset your stomach?”
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ASSESSING ADHERENCE
6. Collaborate with the patient to facilitate adherence
• Review the potential risks of poor adherence
• Set goals (≥ 95% adherence)
• Offer specific suggestions
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PROMOTING ADHERENCE: MEDISAFE
Visual, easy-to-use pill reminder and medication management app
• Free
• iTunes and Google Play
MediSafe reminds patient to take their pillMed-Friend (family member/care-taker) is notified if patient forgets to take pill.
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PROMOTING ADHERENCE: HIVPLUS
Comprehensive HIV treatment resource with daily pill and appointment reminders
• Free
• iTunes and Google Play
Additional features: VL/CD4 tracker, pharmacy finder, health articles, treatment guidelines, clinical trials, complementary and alternative medicine information
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PROMOTING ADHERENCE: GLOWCAP
Gadget fitting over prescription bottle and lights and beeps when dose is due. Sends alert to family members if bottle is not opened.
• $80 + $15/month (AT&T)
• American productAdditional features: Adherence reports, refill request button
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GENERAL PRINCIPLES Successful adherence is an on-going effort Positive reinforcement Maintain open lines of communication Identify barriers to adherence Individualize strategies Non-judgmental approach
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SUMMARY• Drug resistance hinders optimal HIV
management
• Transmitted HIV resistance is an on-going issue
• Different ARV drug classes have different genetic barriers to resistance
• ≥95% adherence is optimal
• Pharmacists are in a position to assess adherence and recommend tools to promote adherent behaviours