Bictegravir/emtricitabine/tenofovir alafenamide in adults with HIV-1 and end-stage kidney disease on chronic haemodialysis

Abstract

Introduction: Treatment for people with HIV-1 and end-stage kidney disease (ESKD) on haemodialysis (HD) has previously required complex dose-adjusted regimens, with limited data on the use of a single-tablet regimen in this population. Our aim was to assess the efficacy and safety of once-daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and to evaluate the pharmacokinetics of bictegravir (BIC) in adults with HIV-1 and ESKD on HD.

Methods: We performed an open-label extension (OLE) of an open-label, multicentre, single-group phase 3b study (NCT02600819) of adults with ESKD on HD and HIV-1 with virological suppression. Participants switched to elvitegravir/cobicistat/F/TAF (E/C/F/TAF) 150/150/200/10 mg for 96 weeks, following which a subgroup of US participants entered an OLE phase in which they switched to B/F/TAF 50/200/25 mg for 48 weeks, returning for study visits at weeks 4 and 12, and every 12 weeks thereafter. Study assessments included virological response, safety and pharmacokinetic analysis of BIC.

Results: Ten participants entered the OLE (median age, 55 years). Virological suppression (HIV-1 RNA <50 copies/mL) was maintained in all participants over 48 weeks of B/F/TAF treatment. B/F/TAF was well tolerated, with no treatment discontinuations. Mean BIC trough concentrations were lower than those previously reported for people with HIV-1 with normal kidney function, but remained four- to seven-fold higher than the established protein-adjusted 95% effective concentration against wild-type HIV-1.

Conclusion: These findings support the use of the once-daily B/F/TAF single-tablet regimen for people with HIV-1 and ESKD on HD. This regimen offers a convenient treatment option for this population as it reduces the need for dose adjustment, eases pill burden and avoids potential drug-drug interactions associated with alternatives that may impact individuals on multiple medications or awaiting transplantation.

Keywords: B/F/TAF; HIV‐1; end‐stage kidney disease; haemodialysis; pharmacokinetics; safety.

FIGURE 1

Concentration of bictegravir (BIC) [bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) plasma pharmacokinetics (PK) analysis set]. ^aMean of sparse timed PK and trough/pre‐dose values where both samples were collected at the same time. ^bUS Food and Drug Administration. Office of clinical pharmacology review–BIKTARVY [14]. paEC95, protein‐adjusted 95% effective concentration; SD, standard deviation.

FIGURE 2

HIV treatment satisfaction at week 48 [HIV Treatment Satisfaction Questionnaire, status version (HIV‐TSQs); bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) safety analysis set]. ^aFor question 2: well controlled and very well controlled; for question 5: convenient and very convenient; for question 6: flexible and very flexible; for question 9: ‘Yes, I would recommend the treatment’ and ‘Yes, I would definitely recommend the treatment’. The survey was completed by 9 of 10 participants at week 48.