Association Between Medication Regimen Complexity and Potential Drug–Drug Interactions Among People Living with HIV: A Prospective Observational Cohort Study

Introduction: The introduction of Combination Antiretroviral Therapy (cART) has substantially improved HIV management, reducing morbidity and mortality while extending life expectancy for People Living with HIV (PLHIV). However, the aging HIV population presents new challenges, including comorbidities and increased medication use leading to polypharmacy, which can compromise treatment adherence and result in adverse outcomes such as hospitalizations and drug reactions. The Medication Regimen Complexity Index (MRCI) provides a quantitative measure to assess medication regimen complexity, considering factors such as dosing frequency and administration instructions. Higher MRCI scores denote more complex regimens, posing challenges to patient adherence. Drug interactions, especially those involving anti-TB drugs and ART, further complicate management, potentially compromising treatment efficacy. Therefore, we examined the associations between MRCI and the number of drug–drug interactions in PLHIV. The findings will inform tailored interventions and support programs by the National AIDS Control Organization (NACO) to optimize treatment outcomes for PLHIV, contributing to public health efforts in India and globally. Methodology: This prospective, observational cohort study was conducted at a medical college-attached teaching hospital in southern India. The study assessed potential drug–drug interactions (pDDIs) by reviewing current prescriptions for interactions among antiretroviral drugs and concomitant medications. Interaction groupings were based on interaction type, interacting medications, clinical implications, and intensity criteria. Results: A total of 285 participants were included, with a median age of 48 years. A positive correlation of moderate-to-strong magnitude was found between average MRCI and the number of pDDIs (unadjusted Spearman ρ = 0.641, p < 0.001), and between baseline MRCI and the number of pDDIs (ρ = 0.575, p < 0.001). In a multivariable Poisson regression adjusting for baseline age, sex, comorbidity burden, co-trimoxazole (TMP-SMX) prophylaxis, CD4 count, viral suppression and antiretroviral regimen class (n = 285), the association between baseline MRCI and baseline pDDI count was attenuated but remained statistically significant (unadjusted IRR 1.068, 95% CI 1.052–1.085; adjusted IRR 1.051, 95% CI 1.031–1.073, p < 0.001), indicating that it is not fully explained by the covariates examined, including ART regimen class. Conclusions: Higher medication regimen complexity was significantly correlated with a greater number of potential drug–drug interactions among PLHIV. As this was an observational study of potential interactions, the findings indicate association rather than causation, and clinical consequences were not confirmed.