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Innovative Adherence
Interventions for
HIV-Infected Youth
Rachel Vreeman, MD, MSAssociate Professor of Pediatrics, Indiana University School of Medicine
Director of Research, Indiana University Center for Global Health and
AMPATH, Kenya
Adherence:
The Central Challenge
• Transformation from terminal illness to chronic
disease
• Suboptimal antiretroviral therapy (ART)
adherence leads to:
• Opportunistic infections
• More severe HIV disease
• Drug resistance
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“Adherence support, rather than
regimen potency, may be the
single most critical determinant
of long-term success [in HIV
treatment].”
Kim JY, Gilks C. Scaling up
treatment – why we can’t wait.
NEJM. 2005;353(22):2392-2394.https://dl.dropboxusercontent.com/u/43279470/Adherence%20Interventions%20Youth_July%202015.docx
Suboptimal Adherence
Common
• Systematic reviews of pediatric ART adherence
in resource-rich and -limited settings reveal high
rates of non-adherence
• Estimates among children in sub-Saharan Africa
suggest 60-80% maintain good adherence
• Evidence adherence declines as children enter
adolescence and young adulthood
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Adolescent Adherence
• Developmental tasks
• HIV disclosure
• Behavioral and mental health
disorders
• Social issues, including HIV
stigma, sexual debut
• Transition to adult care
• Clinically fragile vs. asymptomatic
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Do we know how to improve
adherence for adolescents?
• Not really!
• Few rigorous trials,
particularly in resource-
limited settings
• Existing studies point to
need for multifaceted
adherence
interventions
integrated into routine
healthcare systems
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Categories of Adherence Interventions
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Bhana A, Mellins CA, Petersen I et al. “The VUKA
family program: piloting a family-based psychoso
cial intervention to promote health and mental he
alth
among HIV infected early adolescents in
South Africa.” AIDS Care 2014: 26:1-11
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“Monitoring adherence is
necessary to assess the effect of
interventions and also to inform
providers of the need to implement
interventions.”
Thompson MA, Mugavero MJ, Amico KR, Cargill VA, Chang LW, Gross R, et al.
Guidelines for improving entry into and retention in care and antiretroviral
adherence for persons with HIV: evidence-based recommendations from an
International Association of Physicians in AIDS Care panel. Ann Intern Med.
2012;156(11):817–33.
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https://dl.dropboxusercontent.com/u/43279470/Adherence%20Interventions%20Youth_July%202015.docx
Electronic Dose Monitoring
• Monitoring and
Intervention
• Record time of
opening electronically
• Feedback
opportunities
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Electronic Dose Monitoring
(EDM)• Two recent systematic reviews: evidence for significant
EDM impact on medication adherence (Demonceau, 2013;
Checchi, 2014)
• EDM generally associated with significant improvements in
patient adherence
• Few studies involved children or resource-limited settings
• Adherence improved most when EDM feedback
incorporated into routine care and feedback used to
facilitate patient education and counseling
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Example:• HIV-infected Kenyan children on ART using
Medication Event Monitoring Systems (MEMS,
MWV/AARDEX, Switzerland)
• Suggests EDM significantly improves ART adherence
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Beyond Doses Taken
• Overall high levels of adherence, but potentially
problematic patterns
• Treatment interruptions may be common — and critical
• More non-adherence on EDM than child or caregiver
reports of adherence
• Using MEMS and drug concentrations or PK data:
Pharmacokinetics-Based Adherence Measures for
Antiretroviral Therapy in HIV-Infected Kenyan Children
(Tu et al, Poster 25)
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Dose-Driven Feedback
Demonceau et al, Drugs, 2013
Providing patients with feedback about their own
adherence patterns may be critical:
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What else works?
• Certain SMS and other reminder/monitor devices
• SMS: weekly reminders better than daily
• Real-time monitoring and intervention
“Real-time detection and intervention to terminate
interruptions leads to re-suppression in 86% of cases of
viral rebound.”
Haberer JE et al. Duration of antiretroviral therapy adherence interruption is associated with risk of
virologic rebound as determined by real-time adherence monitoring in Uganda. JAIDS, 2015
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POC Viral Load
• We dream of an inexpensive, point of care viral load test.
However . . .
• May be unique advantages to electronic dose monitoring:
• Marker of medication-taking behavior and not just
clinical outcome
• Entering broader sphere of health behavior
• Interaction about specific challenges, how social
environment impacts adherence
• Promotes dialogue, guides case management and
counseling
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“A patient’s risk of current virological failure,
based on time-updated clinical and MEMS
data, could be made available to clinicians in
real time (e.g., as an automated calculation in
an electronic medical record or smart phone
application) to help determine whether a clinic
visit and/or HIV RNA test is indicated, allowing
for personalized testing and visit schedules.
Our results provide initial proof of concept for
the potential of such an approach to reduce
costs while maintaining outcomes.”
Petersen ML, Super learner analysis of electronic adherence data
improves viral prediction and may provide strategies for selective HIV
RNA monitoring, J. Acquir Immune Defic Syndr 2015 69;109.
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“This ‘red alert’ system
included an extra adherence-
focused education session,
an increased frequency of
counsellor home visits, the
provision of pill boxes and
monthly visits to the clinic.
We showed that 75% of
those who experienced
virological breakthrough
could re-suppress their VL
after this intervention.”
Kaplan et al. March 2014, Vol. 15, No. 1
SAJHIVMED.
The
RIGHT…
information
…
time
…
set of
interventionshttps://dl.dropboxusercontent.com/u/43279470/Adherence%20Interventions%20Youth_July%202015.docx
What do we
want?
• Low patient burden
• Affordable
• Re-usable
• Supply chain friendly
• Works for wide range of
dosing regimens and
packaging formats
• Allows comprehensive
response
• Works for adolescents!