Rifampicin Pharmacokinetics and Clinical Outcomes in Tuberculosis Patients with Comorbidities: A Descriptive Longitudinal Analysis

Abstract

BackgroundTuberculosis (TB) patients with comorbid may experience altered rifampicin pharmacokinetics (PK) particularly in sub-Saharan Africa, affecting treatment response. necessitates a use of therapeutic drug monitoring (TDM) as a tool to identify suboptimal level. We described the rifampicin PK among TB patients with HIV infection, diabetes mellitus, (DM) or malnutrition in Tanzania.MethodsAdult TB patients with comorbidities were enrolled in Kilimanjaro then followed in a longitudinal PK study with sampling at treatment initiation and week 2. Participants received standardized rifampicin, isoniazid, pyrazinamide and ethambutol. Rifampicin PK the area under the concentration-time curve (AUC0-last) and the peak plasma concentration (Cmax) estimated using high-performance liquid chromatography (HPLC) predose at 2±1, 5±1, and 12±3 hours post-dose. Treatment outcomes were assessed at 6 months using World Health Organization definitions.ResultsAmong 40 participants (median age 45 years), Cmax and AUC0-24 declined between visits across all comorbidity groups, with the largest reductions in patients with combined HIV-malnutrition (by 30.3% in Cmax, and 35.3% in AUC0-last). Mixed-effects model showed no clear associations with age, sex, BMI, or malnutrition status, while HIV infection was associated with lower baseline Cmax (-1.83, 95% CI -3.54 to -0.12), and AUC0-last (-5.17, 95% CI -14.77 to 4.44). Six-month outcomes varied by comorbidity, with deaths occurring only among patients with or without malnutrition.ConclusionsThere is a need to integrate enhanced TDM and individualized strategies such as Model-informed precision dosing, supported by clinical decision support systems to optimize rifampicin exposure and improve treatment outcomes for TB patients with comorbidities.