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JAC Advance Access published online on October 5, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl386
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received April 28, 2006
Revised August 29, 2006
Accepted August 30, 2006

Original article

Explaining variability in the relationship between antiretroviral adherence and HIV mutation accumulation

R. S. Braithwaite 1 *, S. Shechter 2, M. S. Roberts 3, A. Schaefer 3, D. R. Bangsberg 4, P. R. Harrigan 5, and A. C. Justice 1

1 Section of General Internal Medicine, Yale University School of Medicine and VA Connecticut Healthcare System, New Haven, CT, USA
2 Department of Industrial Engineering, School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA
3 Department of Industrial Engineering, School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA; Section of Decision Sciences and Clinical Systems Modeling, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4 Epidemiology and Prevention Interventions Center, Division of Infectious Diseases, Positive Health Program, University of California at San Francisco, San Francisco, CA, USA
5 Department of Medicine, University of British Columbia, Vancouver, Canada

* To whom correspondence should be addressed.
R. S. Braithwaite, E-mail: ronald.braithwaite{at}va.gov


  Abstract

Objectives: Determining the relationship between antiretroviral adherence and resistance accumulation is important for the design and evaluation of adherence interventions. Our objective was to explain heterogeneity observed in this relationship.

Methods: We first conducted a systematic review to locate published reports describing the relationship between adherence and resistance. We then used a validated computer simulation to simulate the patient populations in these reports, exploring the impact of changes in individual patient characteristics (age, CD4, viral load, prior antiretroviral experience) on the shape of the adherence-resistance (A-R) curve.

Results: The search identified 493 titles, of which 3 contained relevant primary data and 2 had sufficient follow-up for inclusion (HOMER and REACH cohorts). When simulating HOMER, the A-R curve had a high peak with a greatly increased hazard ratio (HR) of accumulating mutations at partial compared to complete adherence (simulation, HR 2.9; HOMER, HR 2.7). When simulating REACH, the A-R curve had a shallow peak with a slightly increased hazard of accumulating mutations at partial adherence (simulation, HR 1.2; REACH, HR 1.4). This heterogeneity was primarily attributable to differences in antiretroviral experience between the cohorts.

Conclusions: Our computer simulation was able to explain much of the heterogeneity in observed A-R curves.

Keywords: AIDS; HAART; effectiveness; efficacy.
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