The overall goal of the Analytical, Biostatistical and Pharmaceutics Core (Analytical Core C) is to provide support to the DREAM Program with respect to rectal microbicide enema formulation and physical characterization for tenofovir (TFV) and TFV prodrugs (TFV disoproxil fumarate [TDF], TFV alafenamide fumarate [TAF], and CMX157), development and application of quantitative methods for biological sample analysis, and statistical analysis of study data. The operations of Core C focus around the central idea of analysis, with regards to pharmaceutical product formulation (pharmaceutics), drug concentration in biological matrices (analytical), and statistical interpretation of generated data (biostatistical). For bioanalytical studies, Analytical Core C will focus on the development and validation of liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods for the quantification of TFV and TFV prodrugs in plasma, rectal fluid, and tissue. Biopharmaceutical work conducted in Analytical Core C will focus on the development of extemporaneous compounding methods and quality assessments for TFV enema products. The Biostatistical expertise within Analytical Core C will allow the DREAM program to use statistical algorithms to project TFV and TFV prodrug kinetics in the colon. Thus, each area within Analytical Core C will work in tandem to support the pre-clinical and clinical projects of the DREAM program. Analytical Core C has significant experience in the areas of bioanalysis, formulation development, and biostatistical image analysis. Further, Drs. Marzinke (Analytical Core C Leader), Rohan (Analytical Core C Co-Leader) and Caffo have long-standing collaborations with Dr. Craig Hendrix, the principal investigator of the DREAM program. Through the provision of pharmacokinetic data on TDF, TAF, and CMX157, the core will directly support Projects 1, 2 and 3 of this grant proposal. Formulation based efforts provided through this Core will assist Projects 1, 2, 3, &4 as well as Core B.
The DREAM Program proposes development of a high acceptability, easily used TFV enema to overcome the adherence problems encountered in HIV pre-exposure prophylaxis studies. This Core supports the analysis of pharmaceutical product, study samples, and study data to support the development of an enema as rectal microbicide.