Systems Pharmacology Analysis of Multi-Target Drug Interactions in the Chemotherapy of Comorbid HIV and Type 2 Diabetes in Nigerian Patients: A Network-Based Approach

The epidemiological convergence of HIV and Type 2 diabetes mellitus in Nigeria creates a clinically complex polypharmacy scenario in which antiretroviral drugs and antidiabetic agents interact at multiple pharmacological levels, potentially compromising efficacy and safety of both treatment regimens. Existing drug interaction databases inadequately represent population-specific metabolic factors and the biological network context of comorbid disease. This study applied a systems pharmacology and drug-disease network approach to comprehensively characterise multi-target drug interactions in the HIV-T2DM comorbidity context relevant to Nigerian patients. A human drug-target-disease interaction network was constructed by integrating the DrugBank, ChEMBL, and DisGeNET databases. Network topology analysis identified shared molecular nodes between HIV and T2DM biological pathways. Molecular dynamics simulations modelled competitive and allosteric binding interactions between antiretroviral agents and insulin signalling pathway proteins. Nigerian population-specific CYP450 polymorphism frequencies were integrated as Bayesian prior distributions into interaction probability calculations. A pharmacokinetic-pharmacodynamic mathematical model incorporating Nigerian dietary and lifestyle parameters was calibrated against published clinical data. Network analysis identified 18 previously uncharacterised shared drug target proteins between HIV and T2DM pathways. Efavirenz was predicted to competitively inhibit PPAR-gamma at pharmacologically relevant plasma concentrations. The integrated systems model predicted subtherapeutic metformin exposure in 28% of CYP2C8 polymorphism carriers receiving lopinavir/ritonavir. These original computational findings have direct implications for evidence-based prescribing guidelines for HIV-T2DM comorbidity in Nigerian clinical settings. Keywords: systems pharmacology, drug interactions, HIV, Type 2 diabetes, Nigeria.