by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
July 27, 2021
Salama E, Hill L, Patel N, et al. Pharmacokinetics of bictegravir and tenofovir in combination with darunavir/cobicistat in treatment-experienced persons with HIV. J Acquir Immune Defic Syndr. 2021 Jul 19. doi: 10.1097/QAI.0000000000002765. PMID: 34285156.
This single-center prospective study evaluated study-state pharmacokinetics of nine treatment-experienced patients receiving bictegravir/emtricitabine/tenofovir alafenamide plus darunavir/cobicistat as part of routine clinical care at a large, academic HIV clinic. Participants (mean age 59) had been on this combination for at least one month (median duration 16 months), with self-reported study drug adherence. All had creatinine clearance > 30 mL/min and viral load < 200 copies/mL (three participants had CrCl 30-59 mL/min, and five had an undetectable VL). Bictegravir, tenofovir (TFV), TAF, and darunavir profiles were examined pre-dose and then at 0.5hr, 1hr, 2hrs, and 4hrs post-dose. Compared to previously reported PK data, BIC AUC0-tau and Cmax were 26% and 12% higher than BIC/FTC/TAF alone, respectively, while TAF AUC0-tau and Cmax were 165% and 128% higher, respectively. Plasma TFV was modestly higher than historical PK data. Darunavir AUC0-tau was increased by ~20% with a similar Cmax compared to historical data on patients receiving DRV/cobicistat without BIC/FTC/TAF. No adverse events were reported, and no treatment-emergent clinical laboratory abnormalities were observed. All participants maintained viral load < 200 copies/mL. Investigators concluded that, despite modestly higher bictegravir exposure and substantially increased TAF exposure (and modest plasma TFV elevation), co-use of BIC/FTC/TAF plus DRV/cobicistat appeared safe and well-tolerated, suggesting it is a viable option for some PWH.
Drug interaction resources note various increases in ARV exposure with co-administration of bictegravir, darunavir/cobicistat, and TAF. This has introduced an element of clinical uncertainty (especially with regard to potential nephrotoxicity) when co-use has been considered, as the currently available fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide does not allow for TAF dose reduction. Results of this small “real world” study of PWH receiving BIC/FTC/TAF plus darunavir/cobicistat may provide some useful information about the safety of this combination. Further work verifying the reproducibility and generalizability of these observations would be highly welcome—in addition to studies examining overall virological efficacy—as its low pill burden and anticipated potency and durability make it an attractive combination for some treatment-experienced PWH.
The author has no conflicts of interest to disclose.
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