Abstract

This project aims to combine new technologies in mathematical modeling, statistical methods, computer simulations, pharmacokinetics/pharmacodynamics, and clinical/biological sciences in HIV/AIDS research to develop simulation systems for AIDS clinical trials. We expect that the trial simulation systems can help with design of complicated AIDS clinical trials, to optimize sophisticated AIDS treatment strategies, and to study biological mechanisms of HIV infection and AIDS pathogenesis so that new biological hypotheses can be generated for clinical tests. First, mathematical/statistical models will be developed for AIDS clinical trial simulations. These models include drug exposure models for incorporating pharmacokinetics and adherence information, drug sensitivity (resistance) models, drug efficacy and antiviral response models. Statistical methods for estimating model parameters and for making inferences from simulation data will be developed. Based on the established models, computer simulation systems will be developed. Several simulation projects are proposed to test and validate the simulation systems. We expect that the developed AIDS clinical trial simulation systems can be used by AIDS clinicians to design new AIDS clinical trials and to explore new treatment strategies without risking human subjects. AIDS physicians and patients may also use the simulation systems to predict and monitor the outcomes of an antiretroviral treatment. The developed systems will be a useful tool for AIDS clinicians to develop individualized treatments for their patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI055290-06
Application #
7191681
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Gezmu, Misrak
Project Start
2003-09-01
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2009-02-28
Support Year
6
Fiscal Year
2007
Total Cost
$373,346
Indirect Cost

  Institution

Name
University of Rochester
Department
Biostatistics & Other Math Sci
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Miao, Hongyu; Jin, Xia; Perelson, Alan S et al. (2012) Evaluation of multitype mathematical models for CFSE-labeling experiment data. Bull Math Biol 74:300-26
Miao, Hongyu; Xia, Xiaohua; Perelson, Alan S et al. (2011) ON IDENTIFIABILITY OF NONLINEAR ODE MODELS AND APPLICATIONS IN VIRAL DYNAMICS. SIAM Rev Soc Ind Appl Math 53:3-39
Fang, Yun; Wu, Hulin; Zhu, Li-Xing (2011) A Two-Stage Estimation Method for Random Coefficient Differential Equation Models with Application to Longitudinal HIV Dynamic Data. Stat Sin 21:1145-1170
Xue, Hongqi; Miao, Hongyu; Wu, Hulin (2010) Sieve Estimation of Constant and Time-Varying Coefficients in Nonlinear Ordinary Differential Equation Models by Considering Both Numerical Error and Measurement Error. Ann Stat 38:2351-2387
Liang, Hua; Miao, Hongyu; Wu, Hulin (2010) ESTIMATION OF CONSTANT AND TIME-VARYING DYNAMIC PARAMETERS OF HIV INFECTION IN A NONLINEAR DIFFERENTIAL EQUATION MODEL. Ann Appl Stat 4:460-483
Wood, R; Liang, H; Wu, H et al. (2010) Changing prevalence of tuberculosis infection with increasing age in high-burden townships in South Africa. Int J Tuberc Lung Dis 14:406-12
Miao, Hongyu; Dykes, Carrie; Demeter, Lisa M et al. (2009) Differential equation modeling of HIV viral fitness experiments: model identification, model selection, and multimodel inference. Biometrics 65:292-300
Miao, Hongyu; Dykes, Carrie; Demeter, Lisa M et al. (2008) Modeling and estimation of kinetic parameters and replicative fitness of HIV-1 from flow-cytometry-based growth competition experiments. Bull Math Biol 70:1749-71
Wu, Lang; Hu, X Joan; Wu, Hulin (2008) Joint inference for nonlinear mixed-effects models and time to event at the presence of missing data. Biostatistics 9:308-20
Huang, Yangxin; Park, Jeong-Gun; Zhu, Yiliang (2008) Design of long-term HIV dynamic studies using semiparametric mixed-effects models. Biom J 50:528-40

Showing the most recent 10 out of 24 publications