Innovative Adherence Interventions for HIV...

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

https://dl.dropboxusercontent.com/u/43279470/Adherence%20Interventions%20Youth_July%202015.docx

“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


Fischer: Poster 47

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


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


Categories of Adherence Interventions


https://dl.dropboxusercontent.com/u/43279470/Adherence Interventions Youth_July 2015.docx

Poster 47: Fischer

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

“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.


Electronic Dose Monitoring

• Monitoring and

Intervention

• Record time of

opening electronically

• Feedback

opportunities


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


Example:• HIV-infected Kenyan children on ART using

Medication Event Monitoring Systems (MEMS,

MWV/AARDEX, Switzerland)

• Suggests EDM significantly improves ART adherence


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)


Dose-Driven Feedback

Demonceau et al, Drugs, 2013

Providing patients with feedback about their own

adherence patterns may be critical:


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


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


“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.


“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!

Rachel Vreeman: [email protected]

mailto:[email protected]

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