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

Ronald S. Braithwaite, S. Shechter, M. S. Roberts, A. Schaefer, D. R. Bangsberg, P. R. Harrigan, A. C. Justice

Research output: Contribution to journalArticle

35 Scopus citations

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). 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. The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Original languageEnglish (US)
Pages (from-to)1036-1043
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number5
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

Keywords

  • AIDS
  • Effectiveness
  • Efficacy
  • HAART

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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