This proposal intends to develop flexible nonparametric regression methods and statistical inference tools for modeling long-term HIV and T lymphocyte dynamics in HIV-1 -infected patients treated with highly active antiretroviral therapies (HAART). The first specific aim is to develop flexible and efficient nonparametric regression models and inference tools for longitudinal HIV/T-cell dynamic data. These include: (1a) to develop flexible and efficient nonparametric regression methods for longitudinal data. These will include the investigation and extension of local kernel regression methods and basis-based regression splines methods for longitudinal data analysis; (1b) to study the asymptotic and finite-sample properties of the developed nonparametric estimation methods. To compare and evaluate different methods, and to propose the best one for practical use; (1c) to develop statistical inference methods for nonparametric regression models with longitudinal data; (Id) to develop computer programs or software to implement the proposed methodologies.
The second aim i s to apply the developed methods to study long-term HIVTT-cell dynamics using the data from AIDS clinical trials developed by the AIDS Clinical Trials Group (ACTG). These include: (2a) to characterize long-term HIVTT-cell dynamics in HIV-I-infected patients treated with HAART using flexible nonparametric regression methods for longitudinal data, and to study the relationship between long-term HIV dynamics and T lymphocyte kinetics in the environment of long-term antiretroviral drug exposure; (2b) to identify what pharmacological, clinical and host-specific factors affect the long-term dynamics of HIV and T lymphocytes; (2c) to study the relationships between clinical endpoints and the long-term dynamic patterns of HIV and T lymphocytes; (2d) to explore how the long-term HIV/T-cell dynamic patterns can be used to assess the long-term effectiveness of antiretroviral therapies. We may gain more and deep understanding of pathogenesis of chronic HIV infection via modeling the long-term dynamics of HIV and T cells. We expect that the results from this project can be used to assess the long-term effectiveness of antiretroviral therapies and provide information for long-term care and treatment management for HIV-I-infected patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI052765-05
Application #
6868911
Study Section
Special Emphasis Panel (ZRG1-AARR-2 (01))
Program Officer
Gezmu, Misrak
Project Start
2003-08-01
Project End
2008-04-30
Budget Start
2005-05-01
Budget End
2008-04-30
Support Year
5
Fiscal Year
2005
Total Cost
$354,375
Indirect Cost
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
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; 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; Liang, Hua; Wu, Hulin (2008) Identifying significant covariates for anti-HIV treatment response: mechanism-based differential equation models and empirical semiparametric regression models. Stat Med 27:4722-39
Wu, Hulin; Zhu, Haihong; Miao, Hongyu et al. (2008) Parameter identifiability and estimation of HIV/AIDS dynamic models. Bull Math Biol 70:785-99
Liang, Hua; Wu, Hulin (2008) Parameter Estimation for Differential Equation Models Using a Framework of Measurement Error in Regression Models. J Am Stat Assoc 103:1570-1583
Wu, Hulin; Huang, Yangxin; Dykes, Carrie et al. (2006) Modeling and estimation of replication fitness of human immunodeficiency virus type 1 in vitro experiments by using a growth competition assay. J Virol 80:2380-9
Treanor, John; Wu, Hulin; Liang, Hua et al. (2006) Immune responses to vaccinia and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults. Vaccine 24:6913-23
Wu, Hulin; Huang, Yangxin; Acosta, Edward P et al. (2006) Pharmacodynamics of antiretroviral agents in HIV-1 infected patients: using viral dynamic models that incorporate drug susceptibility and adherence. J Pharmacokinet Pharmacodyn 33:399-419

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