A Bayesian Nonparametric Approach for Inferring Drug Combination Effects on Mental Health in People with HIV

Abstract

Although combination antiretroviral therapy (ART) with three or more drugs is highly effective in suppressing viral load for people with HIV (PWH), many ART agents may exacerbate mental health-related adverse effects including depression. Therefore, understanding the effects of combination ART on mental health can help clinicians personalize medicine with less adverse effects to avoid undesirable health outcomes. The emergence of electronic health records offers researchers unprecedented access to HIV data including individuals’ mental health records, drug prescriptions, and clinical information over time. However, modeling such data is challenging due to high-dimensionality of the drug combination space, the individual heterogeneity, and sparseness of the observed drug combinations. To address these challenges, we develop a Bayesian nonparametric approach to learn drug combination effect on mental health in PWH adjusting for socio-demographic, behavioral, and clinical factors. The proposed method is built upon the subset-tree kernel that represents drug combinations in a way that synthesizes known regimen structure into a single mathematical representation. It also utilizes a distance-dependent Chinese restaurant process to cluster heterogeneous population while considering individuals’ treatment histories. We evaluate the proposed approach through simulation studies, and apply the method to a dataset from the Womens Interagency HIV Study, showing the clinical utility of our model in guiding clinicians to prescribe informed and effective personalized treatment based on individuals’ treatment histories and clinical characteristics.