Liverpool HIV Interactions

Potential Interaction

Bictegravir/ Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF)

Darunavir/cobicistat (DRV/c)

Quality of Evidence: Low

Summary:

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with darunavir/cobicistat would be possible from a pharmacokinetic standpoint. Coadministration of bictegravir and darunavir/cobicistat increased bictegravir AUC by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4-fold increase in bictegravir AUC. However, coadministration with darunavir/cobicistat (800/150 mg once daily) and tenofovir alafenamide (25 mg once daily) increased tenofovir AUC and Cmax by 224% and 216%, respectively. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Description:

Biktarvy should not be co-administered with other antiretroviral medicinal products.

Biktarvy Summary of Product Characteristics, Gilead Sciences Ltd, June 2019.

As Biktarvy is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

Biktarvy Prescribing Information, Gilead Sciences Inc, August 2019.

Coadministration of bictegravir (75 mg) and darunavir/cobicistat was studied in healthy subjects (n=15). Coadministration increased bictegravir AUC by 74% due to inhibition of CYP3A4.

Clinical pharmacology of the HIV integrase strand transfer inhibitor bictegravir. Zhang H, Custodio JM, Wei X, et al. Conference on Retroviruses and Opportunistic Infections, Seattle 2017, Abstract 40.

The antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir was evaluated in a phase 1b, randomized, double-blinded, adaptive, sequential cohort, placebo-controlled study. HIV-infected adults not taking antiretroviral therapy were randomized to receive BIC (5, 25, 50, or 100 mg) or placebo once daily for 10 days. Steady-state plasma exposure was approximately dose-proportional up to a 100 mg dose. Bictegravir AUCs on day 10 were 87538 ng.h/ml in the 50 mg group and 178.902 ng.h/ml in the 100 mg group. Bictegravir was safe and well tolerated at all dose levels.

Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1-Infected Adults. Gallant JE, Thompson M, DeJesus E, et al. J Acquir Immune Defic Syndr. 2017, 75(1): 61-66.

The efficacy and safety of bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine was assessed in a double-blind, multicentre, active-controlled, randomised controlled non-inferiority trial. 631 participants were randomly assigned to receive coformulated bictegravir, emtricitabine, and tenofovir alafenamide (n=316) or coformulated dolutegravir, abacavir, and lamivudine (n=315), of whom 314 and 315 patients, respectively, received at least one dose of study drug. At 48 weeks, coformulated bictegravir, emtricitabine, and tenofovir alafenamide achieved virological suppression in 92% of previously untreated adults and was non-inferior to coformulated dolutegravir, abacavir, and lamivudine, with no treatment-emergent resistance. Bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated with better gastrointestinal tolerability than dolutegravir, abacavir, and lamivudine

Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Gallant J, Lazzarin A, Mills A, et al. Lancet. 2017, 390(10107):2063-2072.

In a randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-infected adults were randomly assigned to receive oral fixed-dose combination bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg (n=320)or dolutegravir 50 mg with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg, with matching placebo (n-325), once a day for 144 weeks. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen. Incidence and severity of adverse events were similar between groups, and few participants discontinued treatment due to adverse events (5 [2%] of 320 in the bictegravir group and 1 [<1%] 325 in the dolutegravir group).

Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Sax PE, Pozniak A, Montes ML, et al. Lancet. 2017,390(10107):2073-2082.

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