The objective of this proposal is to link clinical medicine with mathematical modeling in order to design epidemic control strategies for HIV (based upon combination antiretroviral therapies (ARV) and risk reduction) that will maximize public health benefit. We will design epidemic control strategies for the HIV-infected gay community in San Francisco, where the current prevalence of HIV is 30%. We will accomplish our research objective by utilizing three main methodological approaches: developing and analyzing transmission models, fitting transmission models to data, and using novel statistical and phylogenetic analyses to analyze data sets. We have three specific aims: (i) to formulate and analyze new transmission models, (ii) to develop statistical models using existing time dependent sequence data to specify distributions of inputs for the transmission models, and (iii) to use the transmission models to design epidemic control strategies. To complete specific aim 1 we will: (a) formulate a series of new transmission models that can be used to evaluate and to predict the effects of ARV on the epidemic dynamics and the evolution of the HIV epidemic in the gay community in San Francisco, (b) use the models to predict the incidence and the prevalence of drug resistance, (c) incorporate data into the theoretical predictions, and (d) identify which drug-resistance-generating (DRG) mechanisms are the most important in contributing to the emergence and transmission of drug resistant HIV. We will evaluate the contribution of the DRG mechanisms on the epidemic of drug resistant HIV that are due to: the patient, the doctor, the viral strain, and the treatment regimen. To complete specific aim 2 we will: (a) develop a distribution of drug resistant phenotypes using Classification and Regression Trees (CART), and (b) estimate person-specific mutation rates as a function of DRG mechanisms using Bayesian phylogenetic reconstruction. To complete specific aim 3 we will: (a) design detailed epidemic control strategies based upon a variety of evaluation criteria using both medical interventions (ARV) and behavioral interventions (risk reduction), and (b) use the evaluation criteria to evaluate trade-offs between the medical and behavioral interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041935-08
Application #
6859449
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Mckaig, Rosemary G
Project Start
1998-05-01
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
8
Fiscal Year
2005
Total Cost
$577,515
Indirect Cost
Name
University of California Los Angeles
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Palk, Laurence; Blower, Sally (2015) Mapping divided households and residency changes: the effect of couple separation on sexual behavior and risk of HIV infection. Sci Rep 5:17598
Palk, Laurence; Blower, Sally (2015) Brief report: Mobility and circular migration in Lesotho: implications for transmission, treatment, and control of a severe HIV epidemic. J Acquir Immune Defic Syndr 68:604-8
Blower, Sally; Palk, Laurence (2015) Combination HIV prevention and the battle of the sexes. Lancet Infect Dis 15:261-3
Okano, Justin T; Blower, Sally (2014) HIV treatment, preexposure prophylaxis, and drug resistance: reconciling conflicting predictions from mathematical models. J Infect Dis 209:163-4
Gerberry, David J; Wagner, Bradley G; Garcia-Lerma, J Gerardo et al. (2014) Using geospatial modelling to optimize the rollout of antiretroviral-based pre-exposure HIV interventions in Sub-Saharan Africa. Nat Commun 5:5454
Coburn, Brian J; Blower, Sally (2014) Predicting the potential for within-flight transmission and global dissemination of MERS. Lancet Infect Dis 14:99
Coburn, Brian J; Blower, Sally (2013) Mapping HIV epidemics in sub-Saharan Africa with use of GPS data. Lancet Glob Health 1:e251-3
Coburn, Brian J; Okano, Justin T; Blower, Sally (2013) Current drivers and geographic patterns of HIV in Lesotho: implications for treatment and prevention in Sub-Saharan Africa. BMC Med 11:224
Wagner, Bradley G; Coburn, Brian J; Blower, Sally (2013) Increasing survival time decreases the cost-effectiveness of using ""test & treat'' to eliminate HIV epidemics. Math Biosci Eng 10:1673-86
Wagner, Bradley G; Garcia-Lerma, J Gerardo; Blower, Sally (2012) Factors limiting the transmission of HIV mutations conferring drug resistance: fitness costs and genetic bottlenecks. Sci Rep 2:320

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