This project concerns the development of statistical techniques for the analysis of a variety of data sets relating to HIV disease, uterine fibroids and other diseases including STIs. With regard to HIV, we will focus primarily on causal inference techniques for the analysis of randomized trials for HIV prevention. Causal effects of new methods for prevention of HIV infection are complicated by the concurrent use of traditional prevention methods (eg. condoms) in both arms of a trial, and by non-compliance with the randomized intervention and with the other concurrent methods. Second, we will develop statistical methods for modeling time-to-event outcomes with complex features including current status outcomes, competing risks, multiple ordered events or states, measurement error, and partially known or imperfectly measured predictors. These tools will be developed for the purpose of analyzing HIV transmission risk within monogamous sexual partnerships based on cross-sectional samples and extended to apply to linked sexual partnerships with incomplete information on timing and direction of infection events and exposure information, and also generalized to account for missing cause of infection and account for measurement error in exposure data collected in studies of HIV transmission. The use of current status methods for multi- stage disease processes will be extended to address regression relationships between exposure factors and the onset of uterine fibroids based on follow-up information on an existing cohort of Italian women after their environmental exposure to dioxin. These methods can be generalized to studies of HIV infection where various stages of disease progression can be defined and exploited. A common theme underlying all these statistical tools is the joint and causal modeling of the effects of explanatory factors on time-to-event outcomes when there is incomplete information on both outcomes and cofactors, with data that is observational in nature and often high dimensional. The research will be carried out in collaboration with colleagues at the University of California, San Francisco, and other HIV researchers and epidemiologists who will allow access to data from their projects for analysis. The research has considerable relevance to public health in that it will allow the application of modern statistical ideas both to the analysis and interpretation of data (i) from randomized HIV intervention trials with complex intervention assignments and (ii) from observational studies, with incomplete data, of HIV transmission between sexual partners, and the effects of cofactors on disease initiation using disease diagnosis information.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI070043-04
Application #
7866657
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Gezmu, Misrak
Project Start
2007-05-15
Project End
2012-07-31
Budget Start
2010-05-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2010
Total Cost
$308,802
Indirect Cost
Name
University of California Berkeley
Department
Biostatistics & Other Math Sci
Type
Schools of Public Health
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Ng, Hanna H; Stock, Howard; Rausch, Linda et al. (2015) Tenofovir disoproxil fumarate: toxicity, toxicokinetics, and toxicogenomics analysis after 13 weeks of oral administration in mice. Int J Toxicol 34:4-10
Carone, Marco; Asgharian, Masoud; Jewell, Nicholas P (2014) Estimating the lifetime risk of dementia in the Canadian elderly population using cross-sectional cohort survival data. J Am Stat Assoc 109:24-35
Liu, Yashu; Parman, Toufan; Schneider, Bridget et al. (2013) Serum biomarkers reveal long-term cardiac injury in isoproterenol-treated African green monkeys. J Proteome Res 12:1830-7
Alt, Carsten; Harrison, Travis; Dousman, Linda et al. (2009) Increased CCL2 expression and macrophage/monocyte migration during microbicide-induced vaginal irritation. Curr HIV Res 7:639-49
Jewell, Nicholas P (2009) Risk comparisons. Am J Ophthalmol 148:484-6
Page, Kimberly; Hahn, Judith A; Evans, Jennifer et al. (2009) Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection. J Infect Dis 200:1216-26
Rosenblum, Michael; Jewell, Nicholas P; van der Laan, Mark et al. (2009) Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials. J R Stat Soc Ser A Stat Soc 172:443-465
Jewell, Nicholas P (2009) Risk interpretation, perception, and communication. Am J Ophthalmol 148:636-8
Shelton, James D (2007) Diaphragms and lubricant gel for prevention of HIV. Lancet 370:1823;author reply 1823-4
Padian, Nancy S; van der Straten, Ariane; Ramjee, Gita et al. (2007) Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial. Lancet 370:251-61