Significance testing of clinical data using virus dynamics models with a Markov chain Monte Carlo method: application to emergence of lamivudine-resistant hepatitis B virus.
Bayesian analysis using a virus dynamics model is demonstrated to facilitate hypothesis testing of patterns in clinical time-series. Our Markov chain Monte Carlo implementation demonstrates that the viraemia time-series observed in two sets of hepatitis B patients on antiviral (lamivudine) therapy, chronic carriers and liver transplant patients, are significantly different, overcoming clinical trial design differences that question the validity of non-parametric tests. We show that lamivudine-resistant mutants grow faster in transplant patients than in chronic carriers, which probably explains the differences in emergence times and failure rates between these two sets of patients. Incorporation of dynamic models into Bayesian parameter analysis is of general applicability in medical statistics.
Burroughs
N J
NJ
Mathematics Institute, University of Warwick, Coventry, UK. njb@maths.warwick.ac.uk
Pillay
D
D
Mutimer
D
D
D000998:Antiviral Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects; D008390:Markov Chains; D008962:Models, Theoretical; D009010:Monte Carlo Method; D009154:Mutation; D013997:Time Factors; D014766:Viremia; D014779:Virus Replication
D000998:Antiviral Agents; D019259:Lamivudine