This Principal Investigator proposes to develop models and statistical inferential tools for HIV-1 dynamics in vivo. The following specific aims are proposed: (1) to develop HIV-1 dynamic models which are applicable to virological data from AIDS clinical trials; (2) to develop statistical inferential tools for HIV-1 dynamics; (3) to develop statistical methods for assessing the virological response and activities of anti-HIV drugs and treatments using HIV-1 dynamics; (4) to model virological failure and drug-resistance to provide information for treatment and strategies; and (5) to study host-specific factors for viral dynamics. The techniques of approximation and reparameterization of biological compartment models will be used to achieve the first goal. To achieve the second goal, hierarchical nonlinear mixed-effect models will be used. To assess the response to antiviral drugs and treatments, the connection between the HIV-1 dynamic parameters and the drug efficacy will be established and statistical tools for the comparison of treatments based on dynamic parameters will be developed. To achieve the 4th goal, the developed HIV-1 dynamic models will be modified so as to consider the virological failure due to drug resistance and other factors. The covariate selection procedures for nonlinear mixed-effect models will be developed and studied, and then will be used to study host-specific factors for viral dynamics to achieve the last goal. The developed models in vivo and statistical inferential tools for HIV-1 dynamics may be used to accelerate AIDS clinical trials and the development of antiviral drugs. Also, treatment strategies may be studied using HIV-1 dynamic models. Thus, the proposed HIV-1 dynamic models in vivo and statistical inferential methodology will provide a powerful tool to understand the pathogenesis of HIV and to search for a cure for AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI043220-03
Application #
6170494
Study Section
AIDS and Related Research Study Section 2 (ARRB)
Program Officer
Dixon, Dennis O
Project Start
1998-04-01
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$95,900
Indirect Cost
Name
Frontier Sci & Technology Rsch Fdn, Inc
Department
Type
DUNS #
080330186
City
Boston
State
MA
Country
United States
Zip Code
02215
Wu, Hulin (2005) Statistical methods for HIV dynamic studies in AIDS clinical trials. Stat Methods Med Res 14:171-92
Wu, Hulin; Lathey, Janet; Ruan, Ping et al. (2004) Relationship of plasma HIV-1 RNA dynamics to baseline factors and virological responses to highly active antiretroviral therapy in adolescents (aged 12-22 years) infected through high-risk behavior. J Infect Dis 189:593-601
Wu, Hulin; Mellors, John; Ruan, Ping et al. (2003) Viral dynamics and their relations to baseline factors and longer term virologic responses in treatment-naive HIV-1-infected patients receiving abacavir in combination with HIV-1 protease inhibitors. J Acquir Immune Defic Syndr 33:557-63
Huang, Yangxin; Rosenkranz, Susan L; Wu, Hulin (2003) Modeling HIV dynamics and antiviral response with consideration of time-varying drug exposures, adherence and phenotypic sensitivity. Math Biosci 184:165-86
Liang, Hua; Wu, Hulin; Carroll, Raymond J (2003) The relationship between virologic and immunologic responses in AIDS clinical research using mixed-effects varying-coefficient models with measurement error. Biostatistics 4:297-312
Wu, Hulin; Wu, Lang (2002) Identification of significant host factors for HIV dynamics modelled by non-linear mixed-effects models. Stat Med 21:753-71
Wu, Hulin; Zhang, Jin-Ting (2002) The study of long-term HIV dynamics using semi-parametric non-linear mixed-effects models. Stat Med 21:3655-75
Wu, H; Wu, L (2001) A multiple imputation method for missing covariates in non-linear mixed-effects models with application to HIV dynamics. Stat Med 20:1755-69
Wu, H; Connick, E; Kuritzkes, D R et al. (2001) Multiple CD4+ cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highly active antiretroviral therapy. AIDS Res Hum Retroviruses 17:1231-40
Ding, A A; Wu, H (2000) A comparison study of models and fitting procedures for biphasic viral dynamics in HIV-1 infected patients treated with antiviral therapies. Biometrics 56:293-300

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