Drug Interactions Are Crucial in the Care of Patients on Opioid Substitutional Therapy—A Case Report

<b>Background and Clinical significance:</b> This case describes a patient with a complex medical history who develops an active <i>Mycobacterium tuberculosis</i> (MTB) infection. The complex multidrug regimen has led to significant drug-drug interactions (DDIs) and adverse effects. This case highlights an urgent need for standardized guidelines on dose adjustment and therapeutic monitoring for opioid substitution therapy (OST) and antiretroviral therapy (ART) during MTB treatment to prevent adverse health outcomes and ensure clinical success. <b>Case Presentation:</b> A 43-year-old man with medical history including human immunodeficiency virus (HIV), chronic hepatitis C virus (HCV), psychotic disorder, and opioid dependence maintained on buprenorphine (24 mg/day) presented with acute psychosis and respiratory symptoms. During hospitalization, he was diagnosed with MTB infection and was started on an empirical rifampicin-based anti-MTB regimen. His clinical course was complicated by reduced buprenorphine efficacy caused by rifampicin, which precipitated opioid withdrawal symptoms. <b>Conclusions:</b> The successful clinical stabilization with resolution of withdrawal syndrome, reduced agitation, and normalization of vital signs, including heart rate and blood pressure of this patient, was achieved through targeted management of pervasive DDIs. A strategic ART switch and careful buprenorphine dose titration during rifampicin therapy was the key factor. This case highlights that co-managing HIV, MTB, and opioid use disorder presents a significant challenge where unaddressed DDIs directly threaten treatment efficacy, a patient's safety, and adherence, and may result in increased toxicity. The case underscores the critical need for proactive DDI assessment, interdisciplinary collaboration, and guideline development for medication optimization in people living with HIV receiving OST.