Effect of HIV on bedaquiline and delamanid pharmacokinetics in patients with multidrug-resistant TB
Abstract
BACKGROUNDBedaquiline and delamanid are key drugs in the treatment of multidrug-resistant TB. It is unclear whether HIV affects the pharmacokinetics of bedaquiline and delamanid.METHODSParticipants 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.RESULTSTwenty-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.CONCLUSIONHIV 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..
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 49 participants or records.
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