Journal of acquired immune deficiency syndromes (1999) · 2026
The Effect of Rifampicin on the Plasma and Intracellular Pharmacokinetics of Tenofovir Alafenamide Fumarate in HIV-associated Tuberculosis.
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Mpofu Rephaim, Chandiwana Nomathemba, Sokhela Simiso, Moorhouse Michelle, Venter Francois, Anderson Peter L, Wiesner Lubbe, Boffito Marta, Maartens Gary, Sinxadi Phumla
Аннотация
BACKGROUND: Rifampicin reduces plasma tenofovir and intracellular tenofovir diphosphate (TFV-DP) concentrations when coadministered 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 3 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 postcompletion of tuberculosis therapy (TDF-NoRIF). Twenty-four hour area under the concentration-time curves (AUC 0-24h ) were estimated, and geometric mean ratios (GMRs) with 95% confidence intervals were calculated to compare concentrations.
RESULTS: Eighteen participants were enrolled: median age of 42 years; 56% male. The TFV-DP AUC 0-24h GMRs comparing the TAF + RIF treatment period with the TDF + RIF and TDF-NoRIF periods were 5.46 (4.26-7.00) and 5.23 (3.71-7.37), respectively. Plasma tenofovir AUC 0-24h GMR was 0.08 (0.06-0.09) and 0.07 (0.06-0.09) 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.
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 3 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 postcompletion of tuberculosis therapy (TDF-NoRIF). Twenty-four hour area under the concentration-time curves (AUC 0-24h ) were estimated, and geometric mean ratios (GMRs) with 95% confidence intervals were calculated to compare concentrations.
RESULTS: Eighteen participants were enrolled: median age of 42 years; 56% male. The TFV-DP AUC 0-24h GMRs comparing the TAF + RIF treatment period with the TDF + RIF and TDF-NoRIF periods were 5.46 (4.26-7.00) and 5.23 (3.71-7.37), respectively. Plasma tenofovir AUC 0-24h GMR was 0.08 (0.06-0.09) and 0.07 (0.06-0.09) 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.