Prospective HIV Clinical Trial Comparison by Expected Kullback-Leibler Divergence.

Abstract

The sample frequency and volume of blood that can be drawn from a single patient is meticulously restricted under the human subject protection protocols established by an institutional review board (IRB). Consequently, the amount of samples that can be taken during a particular experiment is limited. In order to ensure an effective experiment design, considerations must be taken choosing when to take patient samples. A validated model of HIV-1 viral replication and 2-LTR production is exploited to find sub-optimal sampling schedules that maximize information content of the experiment outcome. This is done through a Forward Stepwise Regression (FSR) process with Kullback Liebler Divergence (KLD) as a selection criterion. Suboptimal schedules are found for an experiment taking four sample points over a possible span of 20 weeks. All schedules found with the FSR process contain significantly more information than both a uniform schedule and a schedule used in a previous experiment with 4 sample points. This work demonstrates the advantages of using KLD as a tool in the experiment design process to increase information content.