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Heterogeneity Among Studies in Rates of Decline of Antiretroviral Therapy Adherence Over Time: Results From the Multisite Adherence Collaboration on HIV 14 Study

Wilson, Ira B. MD, MSc*; Bangsberg, David R. MD, MPH; Shen, Jie PhD; Simoni, Jane M. PhD§; Reynolds, Nancy R. PhD; Goggin, Kathy PhD; Gross, Robert MD, MSCE#; Arnsten, Julia H. MD, MPH**; Remien, Robert H. PhD††; Erlen, Judith A. PhD‡‡; Liu, Honghu PhD*for the Multisite Adherence Collaboration on HIV 14 Investigators

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2013 - Volume 64 - Issue 5 - p 448–454
doi: 10.1097/QAI.0000000000000025
Clinical Science

Objective: To use electronic drug monitoring to determine if adherence to HIV antiretroviral therapy (ART) changes over time, whether changes are linear, and how the declines vary by study.

Design: We conducted a longitudinal study of pooled data from 11 different studies of HIV-infected adults using ART. The main outcome was ART adherence (percent of prescribed doses taken) measured by electronic drug monitoring. We modeled and compared changes in adherence over time using repeated measures linear mixed effects models and generalized additive mixed models (GAMMs). Indicator variables were used to examine the impact of individual studies, and the variation across studies was evaluated using study-specific parameter estimates calculated by using interaction terms of study and time.

Results: The mean age of the subjects was 41 years, 35% were female, most had high school education or less, and 46% were African American. In GAMMs, adherence declined over time. The GAMMs further suggested that the decline was nonlinear, and in both sets of models, there was considerable study-to-study variability in how adherence changed over time.

Limitations: Findings may not be generalizable to non-US populations or to patients not in clinical studies.

Conclusions: Although overall ART adherence declined with time, not all studies showed declines, and a number of patterns of change were seen. Studies that identify clinical and organizational factors associated with these different patterns are needed. Models of changes in adherence with time should take account of possible nonlinear effects.

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*Department of Health Services, Policy & Practice, Brown University School of Public Health, Brown University, Providence, RI;

Massachusetts General Hospital, Center for Global Health; Ragon Institute of MGH, MIT, and Harvard; Harvard Medical School, Boston, MA;

Division of Public Health & Community Dentistry, University of California at Los Angeles School of Dentistry, University of California at Los Angeles, Los Angeles, CA;

§Department of Psychology, University of Washington, Seattle, WA;

School of Nursing, Yale University, New Haven, CT;

Division of Health Services and Outcomes Research, Children's Mercy Hospital and Clinics, University of Missouri – Kansas City, Kansas City, MO;

#Department of Medicine (Infectious Diseases), Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA;

**Department of Medicine, Albert Einstein College of Medicine, Montifiore Hospital, Bronx, NY;

††Department of Psychiatry, Columbia University, New York City, NY; and

‡‡Department of Health and Community Systems, University of Pittsburgh School of Nursing, Pittsburgh, PA.

Correspondence to: Ira B. Wilson, MD, MSc, Department of Health Services, Policy & Practice, Brown University School of Public Health, Brown University, G-121-7, 121 South Main St, Providence, RI 02912 (e-mail:

Supported by the Multisite Adherence Collaboration in HIV (MACH14) grant R01MH078773 from the National Institute of Mental Health, Office on AIDS. The original grants of individual participating studies are R01DA11869, MH54907, 2R01NR04749, R01NR04749, R01MH068197, R01 DA13826, K23MH01862, MH01584, R01 AI41413, R01 MH61173, NIH/NIAID AI38858, AI069419, K02 DA017277, R01DA15215, National Institute of Mental Health P01 MH49548, MH58986, RO1MH61695, CC99-SD-003, CC02-SD-003, and R01DA015679. The content of the paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The authors have no conflicts of interest to disclose.

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Received February 26, 2013

Accepted October 01, 2013

© 2013 by Lippincott Williams & Wilkins