Developing Guidelines for Treatment Adherence,

Entry Into and Retention in Care

Melanie Thompson, MDAIDS Research Consortium of

Atlanta

“Adherence is the Achilles Heel of

Antiretroviral Therapy”

Simoni, et.al. Topics in HIV Medicine, 2003

As in Treatment, So in Prevention Drug levels were a strong correlate of

protection (OR 12.9, p<0.001)◦ 92% reduction in risk with adequate drug levels

To improve treatment outcomes through evidence-based recommendations for ◦Maximizing treatment adherence ◦Optimizing entry into and retention in

care

The Goal of Adherence Guidelines

How much is enough? ◦ Early studies found 90-95% adherence needed to

maintain viral suppression1

◦ Different regimens may require different thresholds of adherence for success2

How is adherence measured and monitored?

◦ Multiple modalities for measurement

◦ No “gold standard” for measurement or monitoring

How can adherence be improved?

◦ Multiple levels for intervention: structural, behavioral, ART regimen, challenges on of special situations (e.g. homelessness, co-morbidities)

Challenges in Understanding Adherence

1Patterson, AIDS, 2000; 2Maggiolo, CID, 2005

Treatment “Adherence” Cascade

Gardner et al. Clin Infect Dis 2011;52.

19% VL<50 c/mL

NO BRAINER #1: If you can’t access care, you cannot access ART – so adherence is irrelevant

Timely entry into care is hampered by late diagnosis…in the USA

Entry Into Care

Not being diagnosed Stigma, fear of discrimination Cost: time off work, visit and med costs Distrust in health care system Multiple “hurdles” to enter a clinic or practice

◦ Residency requirements◦ Adequate documentation of residence or citizenship◦ Distance from home or job◦ Ability to take off time from work

Other competing “life events”: no time for HIV

Entry Into Care

NO BRAINER #2: Continuous access to care is necessary for access to ART

Structural barriers to continuous care◦ Clinic location, hours, rules

◦ Patient’s job, childcare requirements

◦ Cost for visit and medication (including “co-pay”)

Individual barriers

◦ Competing life factors: housing, food, childcare

◦ Co-morbidities: substance abuse, depression, concurrent diseases requiring subspecialist care

◦ Poverty and chaos

Retention in Care

“The empiric data necessary to make strong recommendations regarding the most efficacious way to improve ART adherence are currently lacking.”

“In response to this dearth…a common response from experts has been to recommend strategies based on

methodologically limited data research from adherence in other fields empirically demonstrated correlates of adherence clinical experience

Simoni et al. Topics in HIV Medicine 2003:11(6)

Review of ART Adherence Interventions, 2003

Treatment adherence guidelines have never before been created; research is of varied quality

The science of treatment adherence is cross-cutting, including virology, pharmacology, behavioral science, sociology, technology, and health care implementation and delivery

Entry into and retention in care are an essential component of antiretroviral treatment success, but are complex and have not been well studied

Why Is This Challenging?

Treatment adherence strategies are contextual and may have different outcomes depending on populations and health care settings

Attempt to make global recommendations requires recognition of structural and cultural challenges as well as resource limitations

Why Is This Challenging?

Funding by IAPAC and the US NIH Office of AIDS Research

Invitation of international leaders in antiretroviral therapy and treatment adherence to convene an expert panel

Creation of draft outline

Appointment of section and topic leaders

Guidelines Process

Decisions about appropriate methodology

Decisions regarding recommendations (consensus)

Drafting of document

Publication of guidelines document

Publication of implementation materials as “tool kit”

Guidelines Process

Systematic literature review

◦ Collaboration with CDC’s Prevention Research Synthesis including 45,000 citations between 1996 and 5/2011

◦ Development of literature review strategy

Scope of review: 1996 was beginning of access to HAART

Sources of literature Inclusion criteria and key words

Methodology

Evidence grading processo Hybrid system using selected elements of GRADEo Literature quality scoring by 2 independent

consultantso Panel ultimately responsible for assigning grade

Generation of recommendations by consensus

◦ Strength of recommendation assigned by panel

◦ Justification of recommendations based upon evidence

Methodology

Background & Rationale: Jean Nachega & Melanie Thompson

Methodology: Larry Chang Monitoring and Measurement of Adherence:

Robert Gross Interventions to Promote Adherence:

Michael Mugavero Special Topics: Victoria Cargill Issues Specific To Resource-limited

Settings: Catherine Orrell

Guidelines Content

Interventions to Promote Adherence◦Entry into and retention in care: John

Bartlett◦Antiretroviral treatment strategies:

Michael Mugavero◦Behavioral interventions: K. Rivet Amico◦Structural interventions: Chris Gordon◦Adherence tools: Jim Scott

Guidelines Content, cont’d

Special Topics Affecting Adherence◦ Substance use: Rick Altice◦ Concurrent medical conditions: Princy Kumar◦ Homelessness: David Bangsberg◦ Mental health: Michael Stirrett◦ Incarceration: Curt Beckwith◦ Children and adolescents: Adele Webb◦ Pregnancy: Jean Nachega

Guidelines Content

Frederick Altice, MD Bernard Hirschel, MD

Catherine Orrell, MD

K. Rivet Amico, PhD Charles Holmes, MD Celso Ramos-Filho MD

David Bangsberg, MD Tim Horn Robert Remien, PhD

Magda Barini-Garcia, MD

Shoshana Kahana, PhD

James Scott, Pharm D

John Bartlett, MD Peter Kilmarx, MD Jane Simoni, MD

Curt Beckwith, MD Princy Kumar, MD Kimberly Smith, MD

Victoria Cargill, MD Cindy Lyles, PhD Michael Stirratt, PhD

Larry Chang, MD Rafael Mazin, MD Melanie Thompson, MD

Vanessa Elharrar, MD Henry Masur, MD Evelyn Tomaszewski, MSW

Tia Frazier, RN Michael Mugavero, MD

Marco Vitoria, MD

Christopher Gordon, PhD

Peter Mugyenyi, MD Adele Webb, MD

Robert Gross, MD Jean Nachega, MD

The Panel

Dec 2010: Formative Meeting

Jan 2011: First Panel Meeting: draft outline, writing teams

Feb-Apr 2011: Define Methodology

Apr-July 2011: Literature Review and Evidence Grading

July-Sept 2011: Drafting of Manuscript

Timeline

Publication!

IAPAC: Jose Zuniga PhD, Angela Knudson CDC Prevention Research Synthesis Project:

Cindy Lyles PhD Literature Review and Evidence Grading:

Jennifer Johnsen MD MPH, Laura Bernard MPH, Kathryn Muessig MPH

Funding: US National Institutes of Health, Office of AIDS Research

Acknowledgements