Mathematical and statistical insights in evaluating state dependent effectiveness of HIV prevention interventions

Pre-Exposure Prophylaxis (PrEP) is any medical or public health procedure used before exposure to the disease causing agent, its purpose is to prevent, rather than treat or cure a disease. Most commonly, PrEP refers to an experimental HIV-prevention strategy that would use antiretrovirals to protect HIV-negative people from HIV infection. A deterministic mathematical model of HIV transmission is developed to evaluate the public-health impact of oral PrEP interventions, and to compare PrEP effectiveness with respect to different evaluation methods. The effects of demographic, behavioral, and epidemic parameters on the PrEP impact are studied in a multivariate sensitivity analysis. Most of the published models on HIV intervention impact assume that the number of individuals joining the sexually active population per year is constant or proportional to the total population. In the second part of this study, three models are presented and analyzed to study the PrEP intervention, with constant, linear, and logistic recruitment rates. How different demographic assumptions can affect the evaluation of PrEP is studied. When provided with data, often least square fitting or similar approaches can be used to determine a single set of approximated parameter values that make the model fit the data best. However, least square fitting only provides point estimates and does not provide information on how strongly the data supports these particular estimates. Therefore, in the third part of this study, Bayesian parameter estimation is applied on fitting ODE model to the related HIV data. Starting with a set of prior distributions for the parameters as initial guess, Bayes' formula can be applied to obtain a set of posterior distributions for the parameters which makes the model fit the observed data best. Evaluating the posterior distribution often requires the integration of high-dimensional functions, which is usually difficult to calculate numerically. Therefore, the Markov chain Monte Carlo (MCMC) method is used to approximate the posterior distribution.