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Biostatistics Advance Access published online on March 28, 2006
Biostatistics, doi:10.1093/biostatistics/kxj033
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received September 1, 2005
Revised March 13, 2006
Accepted March 27, 2006

Article

A mutagenetic tree hidden markov model for longitudinal clonal hiv sequence data

Niko Beerenwinkel 1 * and Mathias Drton 2

1 Dept. of Mathematics, University of California, 1073 Evans Hall, Berkeley, CA 94720
2 Dept. of Statistics, The University of Chicago, 5734 S. University Ave., Chicago, IL 60637

* To whom correspondence should be addressed.
Niko Beerenwinkel, E-mail: niko{at}math.berkeley.edu


  Abstract

RNA viruses provide prominent examples of measurably evolving populations. In HIV infection, the development of drug resistance is of particular interest, because precise predictions of the outcome of this evolutionary process are a prerequisite for the rational design of antiretroviral treatment protocols. We present a mutagenetic tree hidden Markov model for the analysis of longitudinal clonal sequence data. Using HIV mutation data from clinical trials, we estimate the order and rate of occurrence of seven amino acid changes that are associated with resistance to the reverse transcriptase inhibitor efavirenz.


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