Effect of HIV on bedaquiline and delamanid pharmacokinetics in patients with multidrug-resistant TB

Shenje J.; Maartens G.; Moran L.; Cramer Y.; Rios J.D.L.; Diacon A.; Dooley K.; Court R. · International Journal of Tuberculosis and Lung Disease (2025) · DOI: 10.5588/ijtld.24.0637

Resumen

BACKGROUND: Bedaquiline and delamanid are key drugs in the treatment of multidrug-resistant TB. It is unclear whether HIV affects the pharmacokinetics of bedaquiline and delamanid. METHODS: Participants with multidrug-resistant TB were randomised to treatment with bedaquiline, delamanid, or both, plus a standard-of-care treatment. Intensive pharmacokinetic sampling was performed after 8 weeks of therapy. We performed non-compartment analysis to describe bedaquiline and delamanid pharmacokinetics, comparing exposures between HIV-positive and HIV-negative participants using geometric mean ratios (GMRs), and explored covariates associated with bedaquiline and delamanid AUC, using multivariable regression modelling. RESULTS: Twenty-six participants were assigned to bedaquiline, 25 received delamanid, and 24 received both drugs. Fifty and 49 participants were treated with bedaquiline and delamanid, respectively. The GMR (90% confidence interval [CI]) of bedaquiline AUC0–22 and Cmax in HIV-positive compared with HIV-negative participants was 0.76 (0.61–0.94) and 0.94 (0.78–1.06), respectively. The GMR (90% CI) of delamanid AUC0–23 and Cmax in HIV-positive compared with HIV-negative participants was 0.93 (0.79–1.09) and 0.79 (0.49–1.27), respectively. CONCLUSION: HIV infection was associated with a 24% reduction in bedaquiline AUC0–22, the significance of which requires further exploration. Delamanid exposure was unaffected by HIV status.