Download Recommendations to Improve Adherence

HIV UPDATE: ADHERENCE ADVANCES WITH
NEW ART FORMULATIONS
Patient Adherence: A Critical Component of HIV
Suppression
Paul E. Sax, M.D.
Clinical Director
Division of Infectious Diseases
Brigham and Women’s Hospital
Professor of Medicine
Harvard Medical School
John T. Brooks, MD
Division of HIV/AIDS Prevention
Centers for Disease Control and Prevention
Disclosures
 John T. Brooks, MD has nothing to disclose.
 Paul Sax, MD, is on the advisory board for
AbbVie, Bristol-Myers Squibb,
GlaxoSmithKline/ViiV, Gilead, Janssen,
Merck. He is a consultant for AbbVie,
Bristol-Myers Squibb, GlaxoSmithKline/ViiV,
Gilead, Janssen, and Merck. He has
provided grants/research for Bristol-Myers
Squibb, GlaxoSmithKline/ViiV, and Gilead.
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Why all the fuss about
adherence and antiretrovirals?
Drugs don’t work in patients
who don’t take them.
— C. Everett Koop, M.D.
Osterberg and Blaschke 2005, N Engl J Med 353:487-97
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HIV Has a Very High Mutation Rate
 HIV in vivo mutation rate
among highest reported
for any biological system
• Most mutations lethal
 High levels of genetic
diversity help HIV:
• Evolve antiretroviral drug
resistance
• Avert immune system
control
• Overcome vaccine
strategies
Cuerva 2015, PLoS Biol DOI:10.1371/journal.pbio.1002251
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Aspects of Non-Adherence
 Adherence is not easily defined
• Fraction of prescribed doses taken per unit time
• Extent to which patients take (or not) medications as
prescribed
• …that is potentially harmful
 Clinician ability to recognize adherence is generally poor
 No currently available tool that can reliably (and at
reasonable cost) predict who will be non-adherent and
when non-adherence is present
 Classically a problem of developed countries, but now
observed in more resource-constrained settings (it’s part
of human nature)
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Non-Adherence with Antiretrovirals
Nonadherence During the Past 48 Hours–United States, Medical Monitoring Project, 2007-2008
Type of Non-Adherence
Percentage
N = 3,307
Dose nonadherence:
Not taking a dose or set of pills/spoonfuls/injections of antiretrovirals
13%
Schedule nonadherence:
Not following a specific schedule for antiretroviral, such as “2 times a day” or “every
8 hours.”
27%
Instruction nonadherence:
Not following special instructions for antiretrovirals, such as “take with food” or
“take on an empty stomach.”
30%
Any of these three types of non-adherence
38%
Beer et al. 2012, Open AIDS J 6(Suppl 1: M21):213-23.
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Reasons for Missed Antiretroviral Therapy Dose, among
Those Ever Missing a Dose—Medical Monitoring Project,
United States, 2013
Percentage
reporting
95% confidence
interval
Forgot to take them
40.0
37.4–42.7
Change in daily routine, including travel
23.9
21.1–26.7
Problem with prescription or refill
14.6
12.7–16.4
Felt sick or tired
12.9
11.0–14.8
Drinking or using drugs
3.0
2.3–3.6
Money or insurance issues
2.8
2.0–3.6
Felt depressed or overwhelmed
2.6
2.0–3.2
Due to side effects of medication
1.3
0.7–1.9
Had too many pills to take
0.7
0.3–1.1
Homeless
0.0
N/A
Reason
CDC 2016, HIV Surveillance Special Report 16. http://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-hssr-mmp-2013.pdf
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Factors Associated with Low Adherence
Comorbidity and psychosocial factors
 Current substance use, including alcohol
 Mental and physical health problems, such as
depression, anxiety, cognitive impairment, and
poor vision
 Low perceived quality of life or life satisfaction
 Lack of social support
 Negative attitudes and beliefs about HIV
disease that may be associated with denial,
nondisclosure, or fear of stigma
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
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Factors Associated with Low Adherence
Knowledge and competence regarding adherence
 Low literacy level regarding health information and
regimen-related instructions
 Lack of knowledge or understanding about 1)
treatment benefits, 2) the importance of sustained
high adherence for health or viral suppression, or 3)
regimen instructions
 Negative attitudes and beliefs about treatment (e.g.,
mistrust, misconceptions, doubts about treatment
effectiveness)
 Low confidence in ability to follow regimen or limited
self-management skills
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
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Factors Associated with Low Adherence
Other
 Multidose or complex regimens
 Side effects
 Chaotic lifestyle or lack of daily
routine
 Lack of attendance at HIV care
visits
 Younger age, male gender,
minority
 Poor patient-doctor relationship
• Cultural competence
• Language barrier
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
Osterberg and Blaschke 2005, N Engl J Med 353:487-97. Claxton et al. 2001, Clin Ther, 23:1296-310. Beer et al. 2014 AIDS Educ Prev 26:521-37.
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Factors Associated with Non-Adherence in Past 48 Hours
United States, Medical Monitoring Project, 2007-2008
Characteristic
Dose
Schedule
Instruction
Male gender
Younger age





Non-Hispanic black race
Educational attainment < high school
Homelessness in past 12 months




Public assistance in the past 12 months


Feeling depressed in past 4 weeks

Crack use in past 12 months
Amphetamine use in past 12 months
Binge drinking in past 30 days


Years since first positive HIV test

Number of ARV doses per day

Don’t know most recent viral load result





Discussed resistance with a health care provider in past 12 months
Beer et al. 2012, Open AIDS J 6(Suppl 1: M21):213-23.
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Factors Associated with Non-Adherence in Past 48 Hours
United States, Medical Monitoring Project, 2007-2008
Characteristic
Male gender
Younger age
Non-Hispanic black race
Educational attainment < high school
Homelessness in past 12 months
Public assistance in the past 12 months
Feeling depressed in past 4 weeks
Crack use in past 12 months
Amphetamine use in past 12 months
Binge drinking in past 30 days
Years since first positive HIV test
Number of ARV doses per day
Don’t know most recent viral load result
Discussed resistance with a health care provider in past 12 months
Beer et al. 2012, Open AIDS J 6(Suppl 1: M21):213-23.
Dose
Schedule















Instruction


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


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Factors Associated with Non-Adherence in Past 48 Hours
United States, Medical Monitoring Project, 2007-2008
Characteristic
Male gender
Younger age
Non-Hispanic black race
Educational attainment < high school
Homelessness in past 12 months
Public assistance in the past 12 months
Feeling depressed in past 4 weeks
Crack use in past 12 months
Amphetamine use in past 12 months
Binge drinking in past 30 days
Years since first positive HIV test
Number of ARV doses per day
Don’t know most recent viral load result
Discussed resistance with a health care provider in past 12 months
Dose
Schedule















Instruction
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




Beer et al. 2012, Open AIDS J 6(Suppl 1: M21):213-23.
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Recommendations to Improve Adherence
Before prescribing assess for and address:
 Patient readiness to start ART
 Misinformation, misconceptions, negative beliefs
 Source(s) of coverage for medication costs
 Mental illness or harmful substance use (e.g.,
binge drinking)
 Social support
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
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Recommendations to Improve Adherence
When prescribing:
 Offer highly effective ART regimens
 Minimize pill burden, dosing frequency,
and dietary restrictions
 Involve patient in decisions about
treatment regimens
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
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Recommendations to Improve Adherence
Confirm understanding in the following areas:
 Dosing (amount and schedule)
 Dietary restrictions
 How to manage missed doses
 Consequences of missing doses (e.g., increased risk of HIVrelated illness, developing drug resistance, transmitting HIV)
 Potential side effects and what to do if side effects occur
 Potential interactions with other prescriptions and
nonprescription products (OTCs, recreational drugs,
supplements)
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
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Recommendations to Improve Adherence
After prescribing routinely assess
 Self-reported adherence using a nonjudgmental
manner
 Side effects
 Patient’s questions, concerns, or challenges
taking ART use to identify potential problems
before virologic failure occurs
 Changes in other prescriptions and
nonprescription products (OTCs, recreational
drugs, supplements)
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
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Recommendations to Improve Adherence
Specific adherence advice to share:
 Link dosing to daily events, such as meals or brushing teeth
 Use pill boxes, dose-reminder alarms, or diaries as
reminders
 Carry extra pills when away from home
 Devise a plan if pill supply is depleted or nearly depleted
 Avoid treatment interruptions when changing routines (e.g.,
travel, legal detention)
Recommendations for HIV Prevention with Adults and Adolescents with HIV in the United States, 2014. http://stacks.cdc.gov/view/cdc/26062.
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CASE PRESENTATION:
Jared
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Jared
 23-year-old man, referred for evaluation after a new HIV
diagnosis
 Last tested negative 2 years prior while in college
 After graduation, traveled around the country with his
boyfriend for several months
 Reports multiple episodes of unprotected receptive anal
sex that occurred mostly during heavy alcohol and
cocaine use
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Jared
 During this trip, had a prolonged “flu” (fever, diarrhea,
fatigue) that resolved spontaneously
 Decided to break up with boyfriend when he returned
home – felt relationship was “unhealthy”
 Decided to seek out pre-exposure prophylaxis from his
PCP – no symptoms at that time
 Baseline evaluation found him to be HIV infected; urine
chlamydia NAAT also positive
 Treated with azithromycin and referred for further
evaluation
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Jared
 Past medical history is notable for 2 episodes of
rectal gonorrhea
 No current medications
 Lives with 2 roommates and works part-time at a
local restaurant
 Binge drinker on his days off; denies current use
of cocaine or other drugs
 Periodic sexual encounters via Grindr app
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What aspect of the case presentation would make you
most worried about medication adherence?
A.
B.
C.
D.
E.
The patient’s young age
Takes no medications
No symptoms
Alcohol and past illicit drug use
Sexually active with multiple partners
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Jared
 Physical exam: Normal
 Labs are done, and patient asked to return
in 1 week to review results
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Jared
 Baseline lab evaluation:
•
•
•
•
•
•
•
CBC and general chemistries: Normal
CD4 = 1100 cells/mL
HIV RNA = 2,500 copies/mL
HLA-B*5701: negative
Genotype: no resistance mutations
HBSAb positive; HAV and HCV negative
Pharyngeal GC NAAT: positive
 Patient misses f/u appointment; cell phone
voice-mail is full
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What would you do next?
A.
Keep trying to call him
B.
Text him using your personal phone
C.
Send a letter to his home address
D.
Contact the Department of Public Health
E.
Show up at his workplace
F.
Nothing – follow-up is his responsibility
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Jared
 Letter sent to his house advising him that
he must return for evaluation
 Ultimately comes in approximately 1
month later
 Treated for GC with ceftriaxone,
empirically for chlamydia as well
 Acknowledges he has been using cocaine
and crystal meth
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Would you start him on ART?
YES
Yes – important for
both his health and for
public health reasons
NO
No – the psychosocial
situation is too unstable,
would focus trying to get
him engaged in substance
use treatment
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Jared
 Despite concerns about follow-up, he is
started on ART
 Scheduled for f/u in 2 weeks to assess
adherence, check safety and efficacy labs
 Misses f/u appointment
 Returns 2 months later – says he’s feeling
fine, taking ART as directed
 HIV RNA 3,100
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What is the most likely explanation?
A.
Antiretroviral drug resistance due to lack
of potency
B.
Patient started ART, then adherence
became poor
C.
Patient never filled prescription
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Case Outcome
 Acknowledges he never filled prescription
 The patient agrees to meet with an addictions
counselor
 Undergoes treatment of underlying depression,
which greatly improves his engagement in care
 Reportedly greatly diminished alcohol and other
drug use
 Fills prescription for ART – now highly motivated to
take it for both his health, and to make
transmission of virus to others less likely
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Stay Tuned for Our Next Session
HIV UPDATE: ADHERENCE ADVANCES WITH
NEW ART FORMULATIONS
Innovations in Antiretroviral Therapy
Formulations
Today from 11:00AM - 12:00PM EST
Speakers
Linda Spooner, PharmD, RPh, BCPS, FASHP
Professor of Pharmacy Practice
Massachusetts College of Pharmacy and
Health Sciences
Paul E. Sax, M.D.
Clinical Director
Division of Infectious Diseases
Brigham and Women’s Hospital
Professor of Medicine
Harvard Medical School
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Thank You