Repeated Measures Longitudinal Analyses of HIV Virologic Response as a Function of Percent Adherence, Dose Timing, Genotypic Sensitivity, and Other Factors

Published in: Journal of Acquired Immune Deficiency Syndromes, v. 41, no. 3, Mar. 2006, p. 315-322

Posted on on January 01, 2006

by Honghu H. Liu, Loren G. Miller, Ron D. Hays, Carol E. Golin, Tongtong Wu, Neil S. Wenger, Andrew H. Kaplan

Read More

Access further information on this document at Journal of Acquired Immune Deficiency Syndromes

This article was published outside of RAND. The full text of the article can be found at the link above.

BACKGROUND: Adherence to antiretroviral medications is critical to achieving HIV viral suppression. Studies have been limited to cross-sectional analyses using measures that reflect only the percentage of prescribed doses taken (percent adherence), however. The contribution of dose timing and other factors to achieving virologic suppression has received less scrutiny. METHODS: In a longitudinal study, the authors collected detailed adherence information using multiple tools along with demographic, clinical, social-behavioral, and virologic measures. Subjects were followed for 48 weeks. Percent adherence, dose-timing, genotypic sensitivity, and virologic outcomes were collected every 4 weeks. Repeated measures mixed effects models (RMMEMs) were used to model the relation between virologic outcomes and adherence as well as genotypic sensitivity and others. RESULTS: Of the 141 subjects, mean percent adherence was 73% with a downward trend. Viral load (VL) dropped significantly (P = 0.01) over time. RMMEMs revealed that higher genotypic sensitivity, higher percent adherence, lower baseline VL, longer inclusion in the study, earlier HIV stage, and smaller dose-timing error were significantly associated with lower VL. In multivariate modeling, a 0.50 increase in the genotypic sensitivity score, a 10% increase in adherence, and a decrease of 3 hours of dose-timing error were associated with a decrease in log10 HIV RNA at 48 weeks of 0.69, 0.54, and 0.48, respectively (P < 0.05 for each). CONCLUSIONS: Long-term viral suppression requires consistent and high percent adherence accompanied by optimal interdose intervals. Efforts to improve viral outcomes should address not only missed doses but excessive variation in dose timing and prevention of adherence decline over time. Preventing the development and transmission of resistant variants is also critically important.

This report is part of the RAND Corporation External publication series. Many RAND studies are published in peer-reviewed scholarly journals, as chapters in commercial books, or as documents published by other organizations.

The RAND Corporation is a nonprofit institution that helps improve policy and decisionmaking through research and analysis. RAND's publications do not necessarily reflect the opinions of its research clients and sponsors.