Sustained Benefit from a Long-term
Antiretroviral (AR) Adherence Intervention:
Results of a Large
Randomized Clinical Trial
CPCRA 062: “Adherence Strategies
Using a Medication Manager and
an Electronic Medication Reminder System
for HIV-Infected Patients Receiving HAART”
Sharon Mannheimer*, Edward Morse, John Matts, Laurie Andrews,
Carol Miller, Barry Schmetter and Gerald Friedland for the Terry Beirn
Community Program for Clinical Research on AIDS (CPCRA)
Late Breakers Track B, Abstract LbOrB15
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Background
• AR adherence associated with many benefits:
– Better virologic outcome
– Better immunologic outcome
– Less progression of HIV disease
– Fewer hospitalizations
– Better quality of life
– Lower mortality
• Suboptimal adherence common
• Very few interventions to improve adherence
have been studied in randomized controlled
trials
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Presentation today will focus on:
Primary Results of CPCRA* 062:
• 928 participants co-enrolled from CPCRA FIRST
protocol (CPCRA 058), an AR trial for AR-naïve
persons with HIV; FIRST participants randomized to:
» PI-based regimen
» NNRTI-based regimen
or
» PI + NNRTI-based regimen
• Enrollment November 1999 through January 2002
• Follow-up through June 2003
*CPCRA = Community Programs for Clinical Research on AIDS, an
NIAID-funded HIV clinical trials network C•P•C•R•A
Purpose
To evaluate the effects of
two adherence interventions:
(1) Medication Manager
(2) Electronic medication reminder
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Medication Manager Intervention
• Based on Information-Motivation-Behavioral Skills*
theoretical model
• “Medication Manager” is a trained research staff
member who provided tailored adherence support:
– Comprehensive standardized baseline assessment
– Individualized adherence support plans
– Contact w/ pts. weekly for 4 weeks, then at least monthly
– Observe pillbox use
– Standardized follow-up assessments every 4 months
*Fischer JD, et al. Heath Psychol 1994;13:238-50
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Electronic Medication Reminder
Intervention
• ALR™ = “A Little Reminder”
(Timely Devices Incorporated; Edmonton, Alberta)
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Study Endpoints
Primary
• Time to first virologic failure* defined as:
first plasma HIV RNA level > 2,000 copies/mL
occurring at or after the 4-month follow-up visit
Secondary
• Percent of patients with HIV RNA 2000) between primary comparison
groups
• Primary endpoint analyzed by life table
analysis taking into account the clustering
• Secondary endpoints analyzed by repeated
measures analysis
• Intent-to-treat analysis
*Power of at least 0.80 and a 0.05 two-sided level of significance C•P•C•R•A
Baseline Characteristics
N = 928
Age, mean yrs. 38
Female 22%
Nonwhite 75%
Prior AIDS 38%
Prior IV drug use 15%
CD4 lymphocyte count,
median cells/mm3 155
Log HIV RNA, median 5.2
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Results
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Primary Endpoint
Time to First HIV RNA >2000 Copies/mL at or after 4-Month Visit
Event Rate per 100 person years
No MM MM
No ALR™ 30.4 28.2
ALR™ 41.6 33.3
P-value for interaction = 0.51
MM = Medication Manager
ALR™ = Electronic reminder device
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Medication Manager Effect
Primary Endpoint:
Time to First HIV RNA >2000 Copies/mL at or after 4-Month Visit
MM p=0.13
No MM
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Medication Manager Effect on HIV RNA:
Percent of Patients with HIV RNA 2,000 0.87 (favor MM) 0.13
copies/mL at or after 4-Month
visit
Secondary Endpoints Odds Ratio
% HIV-RNA 2000 copies/mL at or after 4-Month Visit
ALR p=0.02
No ALR
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ALR Effect on HIV RNA:
Percent of Patients with HIV RNA 2,000 1.25 (favor No ALR) 0.02
copies/mL at or after 4-Month
visit
Secondary Endpoints Odds Ratio
% HIV-RNA < 50 copies/mL 1.03 (no difference) 0.73
% patients reporting 100% 0.90 (no difference) 0.25
adherence
Difference
CD4, mean change from -2.6 (no difference) 0.77
baseline (cells/mm3)
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Summary
• Medication Manager associated with:
–Trend toward lower risk of virologic failure
(13% lower)
–Greater CD4 cell increase (overall +23 cells)
–Improved self-reported adherence
–Sustained benefit over time
• No benefit associated with ALR
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Conclusions
• The CPCRA Adherence study is the largest
randomized controlled trial of adherence
interventions in persons with HIV
• Medication Manager use was associated with
improved outcomes among antiretroviral-naïve
patients initiating therapy
• No benefit was seen with the electronic reminder
• The study results support the use of this
standardized medication manager intervention
to promote antiretroviral adherence
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Acknowledgements
CPCRA 062 participants CPCRA 058 (FIRST) team
Rodger D. MacArthur, Chair
CPCRA 062 team members
Sharon Mannheimer, Co-Chair CPCRA Statistical Center
Edward Morse, Co-Chair John Matts
Laurie Andrews Carol Miller
Lynn Besch Glenn Bartsch
Barbara Brizz Grace Peng
Judith Brooks Li Chen
Linda Budan Ying Xiang
Carroll Child
Noreen Choudhry CPCRA Operations Center
Marjorie Dehlinger Caron Lee
Elaine Ferguson Barry Schmetter
Gerald Friedland
Johnnie Jenkins Patricia Simon-Morse CPCRA sites & staff
John Matts Marie Sioud
Carol Miller Bentley Sweeton
Nancy Reilly Ellen Tedaldi
Barry Schmetter Robert Vallier
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Medication Managers
Antonio Alexander Pamela Gorman Paula Pell
Philip Andrew Carol Graeber Sue Peterson
Cristina Baroni Lynne E. Green Kevin Pierson
Dale E. Britt Kerry Griscti Jonathan Prevost
Susan P. Caras Martha L. Howe Lena Richardson-Wells
Carol S. Clark Maria Tadea Insignares James Robinson
Rosetta Contreras Karen Lambert Jones Marlana Robinson
Kimberly L. Cosby-McCargo Michael Jones Victoria Rudzik
Richard Cratty Karen L. Kaufmann Helen May Seedhom
Pierre-Cedric B. Crouch Nancy Kimmel Sandy Sheble-Hall
Leith Daley Karen Loveless Paulette Dawn Slowinski
Brenda Devarie Robert Manning Diane States
Patricia W. Dodson Norma Martinez Suzanne M. Sweek
Eileen Dolce Lillian Mercado Candace L. Tobin
Jairo Eraso Mark Miller Dominick P. Varsalone
Martha Farrough Dolores Milnes Luz Marina Vasco
Deborah Goraj Jorge Camilo Mora Vicky W. Watson
Frances Moran Julia Weise