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Register a new userA Bayesian Nonparametric Approach for Inferring Drug Combination Effects on Mental Health in People with HIV
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Wei Jin
Publication date
2020
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Mathematical Statistics
and research's language is
English
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Although combination antiretroviral therapy (ART) is highly effective in suppressing viral load for people with HIV (PWH), many ART agents may exacerbate central nervous system (CNS)-related adverse effects including depression. Therefore, understanding the effects of ART drugs on the CNS function, especially mental health, can help clinicians personalize medicine with less adverse effects for PWH and prevent them from discontinuing their ART to avoid undesirable health outcomes and increased likelihood of HIV transmission. 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 very challenging due to high-dimensionality of the drug combination space, the individual heterogeneity, and sparseness of the observed drug combinations. 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 method 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 taking into account individuals treatment histories. We evaluate the proposed approach through simulation studies, and apply the method to a dataset from the Womens Interagency HIV Study, yielding interpretable and promising results. Our method has clinical utility in guiding clinicians to prescribe more informed and effective personalized treatment based on individuals treatment histories and clinical characteristics.
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Access and adherence to antiretroviral therapy (ART) has transformed the face of HIV infection from a fatal to a chronic disease. However, ART is also known for its side effects. Studies have reported that ART is associated with depressive symptomatology. Large-scale HIV clinical databases with individuals longitudinal depression records, ART medications, and clinical characteristics offer researchers unprecedented opportunities to study the effects of ART drugs on depression over time. We develop BAGEL, a Bayesian graphical model to investigate longitudinal effects of ART drugs on a range of depressive symptoms while adjusting for participants demographic, behavior, and clinical characteristics, and taking into account the heterogeneous population through a Bayesian nonparametric prior. We evaluate BAGEL through simulation studies. Application to a dataset from the Womens Interagency HIV Study yields interpretable and clinically useful results. BAGEL not only can improve our understanding of ART drugs effects on disparate depression symptoms, but also has clinical utility in guiding informed and effective treatment selection to facilitate precision medicine in HIV.
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