Biktarvy®
Bictegravir 50 mg / Emtricitabine 200 mg / Tenofovir alafenamide 25 mg
Fabricant : Gilead
1 tablet DIE with or without food
1 tablet DIE with or without food for children or adolescents ≥ 25 kg
Pediatric population < 25 kg : Not recommended because safety and efficacy have not been established
CrCl ≥ 30 mL/min : No adjustment required
CrCl < 30 mL/min : Administration not recommended due to lack of data (Study in progress)
CrCl < 15 mL/min (chronically treated with hemodialysis): No adjustment necessary, administration after treatment sessions on the day of hemodialysis
CrCl < 15 mL/min (not chronically treated with hemodialysis): Administration not recommended due to lack of data
No data are available on which to make a dosage recommendation in pediatric patients with renal impairment
Child-Pugh A or B : No adjustment required
Child-Pugh C : Administration not recommended (not studied in this population)
Biktarvy® has been studied in treatment-naive patients as well as in patients undergoing treatment with virological suppression and having no documented resistance.
Study |
Comparator groups |
Efficacy results (reaching a viral load < 50 copies/mL at 96 weeks) |
| GS-US-380-1489 | BIC/FTC/TAF (N=314) vs DTG/ABC/3TC (N=315) | Noninferiority of BIC/FTC/TAF (88% vs 90%, 95% CI -6.9% at 3.1%) |
| GS-US-380-1490 | BIC/FTC/TAF (N=282) vs DTG + FTC/TAF (N=297) | Noninferiority of BIC/FTC/TAF (84% vs 86%, 95% CI -7.9% at 3.2%) |
Study |
Comparator groups |
Efficacy results (reaching a viral load < 50 copies/mL at 48 weeks) |
Types of patients |
| GS-US-380-1844 | BIC/FTC/TAF (N=282) vs continue DTG/ABC/3TC (N=281) | Noninferiority of BIC/FTC/TAF (1% vs <1%, 95% CI -1.0% à 2.8%) | Virologic suppression for ≥ 3 months; majority with CD4+ ≥ 500 cells/µL; No documented or suspected resistance to DTG, ABC, 3TC, FTC or tenofovir |
| GS-US-380-1878 | BIC/FTC/TAF (N=290) vs continue boosted PI (DRV or ATV) + ABC/3TC or TDF/FTC (N=287) | Noninferiority of BIC/FTC/TAF (2% vs 2%) | Virologic suppression for ≥ 6 mois; majority with CD4+ ≥ 500 cells/µL; No documented or suspected resistance to FTC, tenofovir, ABC or 3TC |
This ongoing observational study aims to demonstrate the efficacy, safety and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in 1,400 people living with HIV in Germany, Canada, France and the Netherlands. At the time of data collection (March 2020), 513 patients receiving BIC/FTC/TAF (n=84 naive/n=429 experienced) had completed a 12 months visit. A high level of efficacy and safety was observed in both male and female participants, including older people. 100% of naive participants and 96% of experienced patients had a viral load <50 copies/mL. No major resistance substitution for the components emerged. Drug-related adverse reactions occurred in ~15% of participants, the most common being gastrointestinal (5%) and neuropsychiatric (4%).
GS-US-380-1489 Study (week 96)
|
||
| BIC/FTC/TAF | DTG/ABC/3TC | |
| Nausea | 11% (6%) | 24% (17%) |
| Diarrhea | 15% (6%) | 16% (4%) |
| Headache | 13% (5%) | 16% (5%) |
| Fatigue | 9% (< 5%) | 11% (< 5%) |
| Back pain | 8% (< 5%) | 10% (< 5%) |
| Insomnia | 7% (< 5%) | 10% (< 5%) |
GS-US-380-1490 Study (week 96)
|
||
| BIC/FTC/TAF | DTG + FTC/TAF | |
| Nausea | 9% | 11% |
| Diarrhea | 18% | 16% |
| Headache | 16% | 15% |
| Fatigue | 8% | 10% |
| Back pain | < 10% | < 10% |
| Insomnia | < 10% | < 10% |
Among these two studies, ≤ 3% of patients discontinued study drug due to adverse events or death (week 96).
For management of adverse reactions associated with antiretrovirals, see section management of adverse reactions.
Bictegravir increases the serum concentration of creatinine via an inhibition of tubular secretion. This should not be interpreted as an impairment of kidney function. The increase usually occurs within the first four weeks of treatment and is, on average, around 10 μmol/L. This should be taken into account when estimating a patient’s kidney function. Some will subtract the serum creatinine observed when adding bictegravir before calculating the estimated glomerular filtration rate.
An increase of grade 3-4 has been observed in 4% of the participants.
Grade 1 : 9% (bilirubin); grade 2: 3% (bilirubin); grade 3-4 : 2% (AST) 1% (ALT).
No discontinuation of treatment due to hepatic adverse events through Week 48.
Integrase inhibitor
Nucleoside reverse transcriptase inhibitors
Bictegravir : 2-4 h
Emtricitabine : 1.5-2 h
Tenofovir alafenamide : 0.5-2 h
* Values reflect administration of BIKTARVY® with or without food
Bictegravir : 17.3 h
Emtricitabine : 10 h
Tenofovir alafenamide : 0.51 h (tenofovir 32.37 h)
Tenofovir alafenamide : 150-180 h in mononuclear peripheral blood cells
Bictegravir : > 99 %
Emtricitabine : > 4 %
Tenofovir alafenamide : ~80 %
Bictegravir : CYP3A and UGT1A1 (similar contributions)
Emtricitabine: not significantly metabolized
Tenofovir alafenamide : cathepsin A and CES1; transported by P-gp and BCRP
Bictegravir : Hepatic
Emtricitabine : ~86 % urinary excretion and ~14 % unchanged in faeces
Tenofovir alafenamide : Hepatic
There is not enough data to assess safety and effectiveness of Biktarvy® in pregnant or breastfeeding women.
Professionals are encouraged to report pregnancy cases with a view to adding them to the register:
www.apregistry.com/ Telephone : 1-800-258-4263 Fax : 1-800-800-1052.
Patient co-infected with hepatitis B
Administration with other antiretrovirals
See product monograph and interactions module for further details.
A study in 18 healthy volunteers (Hoqueloux L et al, 2021) showed that Biktarvy® tablet dissolved in water caused a very modest increase and decrease in the bioavailability of bictegravir and tenofovir alafenamide, respectively. The crushed tablet in applesauce resulted in reduced bioavailability of tenofovir and emtricitabine compared to the whole tablet. Based on these data, Biktarvy® could be administered dissolved in water for patients with swallowing difficulties, provided that TDM of bictegravir and tenofovir is performed for prolonged administration.
There are two case reports of the administration of crushed Biktarvy® tablets.
The first case, a 64-year-old man with significant dysphagia secondary to esophageal cancer. The viral load remained undetectable for 10 months with the administration of crushed Biktarvy® in 30 to 60 ml of water via the PEG tube followed immediately after the administration of 240 ml of an enteral formula (Jevity 1.2). (Fulco PP et al, 2020).
The second case, a 39-year-old woman with dysphagia due to progressive multifocal leukoencephalopathy. An adequate virologic response of 4 weeks (decreased from 1,023,292 to 1,084 copies / mL) and then with Biktarvy® crushed and administered as a solution via the nasogastric tube for 6 weeks. However, 12 weeks after starting Biktarvy®, the patient’s viral load increased and several mutations appeared (M184V, L74I and R263K). It is not known whether the failure of Biktarvy® is due to previous exposure to antiretrovirals (with failure and resistance) or administration of the crushed Biktarvy® tablet (Lozano AB et al, 2020).
For the company, the data is currently insufficient and they recommend against cutting or crushing the tablet and swallowing it whole.
Store the tablets below 30° C.
BIC, bictegravir; FTC, emtricitabine; TAF, tenofovir alafenamide; DIE, once daily; CrCl, creatinine clearance; DTG, dolutegravir; ABC, abacavir; 3TC, lamivudine; DRV, darunavir; ATV, atazanavir; TDF, tenofovir disoproxil fumarate.
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