Population kinetic modelling of metabolic traits in HIV-infected individuals

Background: Metabolic complications are an increasing concern in aging HIV-positive individuals. Previous studies were limited by their static design. Here we propose to adopt a well validated population pharmacokinetics methodology that allows analysing large datasets of multiple metabolic laboratory markers, gene variants and phenotypes longitudinally and simulating appropriate strategies for patient care.

Study Aims: To develop a population kinetics model to describe the dynamics and interindividual variability of metabolic traits after ART initiation, taking into consideration demographic, genetic and non-genetic covariates and common ART regimens. To perform model-based simulations of appropriate clinical strategies for metabolic risk management.

Study Design: We will model 10 metabolic traits in 1152 SHCS participants; genotyping will be with a custom designed array containing 3072 genetic variants associated with these metabolic complications in the general population. We will use 3 different modelling approaches depending on type of endpoint (concentration-time, response-time or time to event).