Background: Rifampicin reduces plasma tenofovir and intracellular tenofovir diphosphate (TFV-DP) concentrations when co-administered with tenofovir alafenamide fumarate (TAF). Standard-dose TAF with rifampicin still provided higher TFV-DP concentrations than tenofovir disoproxil fumarate (TDF) in a healthy volunteer study, but this interaction has not been assessed in people with HIV-associated tuberculosis.
Setting: Open label, three-period pharmacokinetic study in participants with HIV-1 on tenofovir based ART (plus emtricitabine and efavirenz) in the maintenance phase of weight-based tuberculosis therapy.
Methods: Concentrations of intracellular peripheral blood mononuclear cell TFV-DP and plasma tenofovir were measured during three treatment periods: 1) TDF 300 mg daily and rifampicin (TDF + RIF), 2) TAF 25 mg daily and rifampicin (TAF + RIF), and 3) TDF without rifampicin post-completion of tuberculosis therapy (TDF-NoRIF). Twenty-four hour area under the concentration-time curves (AUC0-24h) were estimated, and geometric mean ratios (GMR) with 95% confidence intervals were calculated to compare concentrations.
Results: Eighteen participants were enrolled: median age of 42 years; 56% male. The TFV-DP AUC0-24h GMRs comparing the TAF + RIF treatment period with the TDF + RIF and TDF-NoRIF periods were 5.46 (4.26 to 7.00) and 5.23 (3.71 to 7.37), respectively. Plasma tenofovir AUC0-24h GMR was 0.08 (0.06 to 0.09) and 0.07 (0.06 to 0.09) when comparing TAF + RIF with the TDF + RIF and TDF-NoRIF periods, respectively.
Conclusions: When combined with rifampicin, ART containing standard-dose TAF resulted in higher TFV-DP concentrations than TDF-based ART in participants with HIV-associated tuberculosis, supporting its use with rifampicin-containing tuberculosis therapy.
Keywords: HIV-associated tuberculosis; drug-drug interaction; pharmacokinetics; rifampicin; tenofovir alafenamide fumarate; tenofovir diphosphate.
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