Pharmacokinetics of Twice-daily Tenofovir Alafenamide in Adults With HIV-associated Tuberculosis on Bictegravir/Emtricitabine/Tenofovir Alafenamide and Rifampicin.

BACKGROUND

Tenofovir alafenamide (TAF) is a key component of many fixed-dose combinations used to treat HIV. There are limited data on the pharmacokinetics of plasma TAF, tenofovir (TFV), or intracellular tenofovir diphosphate (TFV-DP), among people with HIV (PWH) and tuberculosis (TB) who are taking rifampicin-based TB treatment.

METHODS

Participants in the intervention arm of the INSIGHT trial (NCT04734652) receiving bictegravir/emtricitabine/TAF (BIC/FTC/TAF 50/200/25 mg) were enrolled into the semi-intensive pharmacokinetic substudy. BIC/FTC/TAF was administered twice-daily during rifampicin-based TB treatment (∼24 weeks) and once-daily thereafter. Plasma (TAF/TFV) and dried blood spot samples (TFV-DP) were collected at weeks 4 and 12 (predose, 1, 2, 4, 6, and 8-12 hours postdose) during TB treatment and at week 32 (predose, 1, 2, 4, 6-8 and 24-25 hours postdose) post-TB treatment. Pharmacokinetic parameters were determined using noncompartmental analysis. Clinical and safety data were collected.

RESULTS

Among 43 participants enrolled; median (IQR) age and weight were 35 (30-39) years and 58 (52-65) kg; 77% were male. Geometric least square mean ratios (90% CI) at week 12 (twice-daily TAF) relative to week 32 (once-daily TAF) for TAF AUC0-4, TFV, and TFV-DP AUC0-24 were 1.55 (1.13-2.13), 1.24 (1.07-1.44), and 1.32 (1.13-1.53), respectively. At week 24, 95% of participants achieved viral suppression, with no treatment-related serious adverse events or drug discontinuations.

CONCLUSIONS

Twice-daily TAF was safe and efficacious and achieved similar exposures of intracellular TFV-DP in PWH taking rifampicin for TB compared to once-daily TAF taken alone. These data support the use of TAF in a fixed-dose combination of BIC/FTC/TAF during rifampicin-containing TB treatment.