Cette page a été mise à jour le 2 September 2021

FORMULATION(s)

Fabricant : Gilead

DOSAGE

Adult dosage

1 tablet DIE with or without food

Pediatric dosage

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

Adjustment in renal impairment

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

Adjustment in hepatic impairment

Child-Pugh A or B : No adjustment required

Child-Pugh C : Administration not recommended (not studied in this population)

COMPARATIVE EFFICIENCY

Biktarvy® has been studied in treatment-naive patients as well as in patients undergoing treatment with virological suppression and having no documented resistance.

Studies in patients who have never received antiretrovirals

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%)

Studies in patients with virological suppression and no documented resistance

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

Real-world clinical cohort study in antiretroviral therapy-naive and experienced patients – BICSTaR

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%).

ADVERSE REACTIONS

In short

  • Nausea
  • Headaches
  • Insomnia
  • Fatigue
  • Diarrhea
  • Weight gain

GS-US-380-1489 Study (week 96)
Adverse reactions reported in > 10% of participants
(Associated with drug and reported in ≥ 5%)

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)
Adverse reactions reported in ≥ 10% of participants

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.

IMPACT ON LABORATORY

Creatinine increase

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.

Impacts observed in studies GS-US-380-1489 and GS-US-380-1490

CK increase

An increase of grade 3-4 has been observed in 4% of the participants.

Bilirubin/AST/ALT increase

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.

MECHANISM OF ACTION

Bictegravir

Integrase inhibitor

Emtricitabine and tenofovir alafenamide

Nucleoside reverse transcriptase inhibitors

PHARMACOKINETICS

Tmax

Bictegravir : 2-4 h
Emtricitabine : 1.5-2 h
Tenofovir alafenamide : 0.5-2 h
* Values reflect administration of BIKTARVY® with or without food

Elimination T½ (plasma)

Bictegravir : 17.3 h
Emtricitabine : 10 h
Tenofovir alafenamide : 0.51 h (tenofovir 32.37 h)

Intracellular T½

Tenofovir alafenamide : 150-180 h in mononuclear peripheral blood cells

Binding to plasma proteins

Bictegravir : > 99 %
Emtricitabine : > 4 %
Tenofovir alafenamide : ~80 %

Metabolism

Bictegravir : CYP3A and UGT1A1
Emtricitabine: not significantly metabolized
Tenofovir alafenamide : cathepsin A and CES1; transported by P-gp and BCRP

Elimination

Bictegravir : Hepatic
Emtricitabine : ~86 % urinary excretion and ~14 % unchanged in faeces
Tenofovir alafenamide : Hepatic

PREGNANCY AND BREAST FEEDING

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.

PRECAUTIONS AND CONTRAINDICATIONS

Precautions

Patient co-infected with hepatitis B

  • If Biktarvy® is discontinued in a patient co-infected with HBV, caution should be exercised. Indeed, severe acute exacerbations of hepatitis B (hepatic decompensation and hepatic failure) have been observed in patients co-infected with HBV and HIV-1. Therefore, stopping treatment with Biktarvy® without initiating alternative hepatitis B therapy is not recommended.

Administration with other antiretrovirals

  • Biktarvy® should not be coadministered with other antiretrovirals that contain bictegravir, emtricitabine, tenofovir alafenamide, tenofovir DF or lamivudine (Atripla, Combivir, Complera, Delstrigo, Descovy, Dovato, Emtriva, Epivir, Heptovir, Genvoya, Kivexa, Odefsey, Symtuza, Stribild, Triumeq, Trizivir, Truvada, Vemlidy, Viread), nor with adefovir dipivoxil (Hepsera).

Contraindications

  • Hypersensitivity to the active or inactive molecules contained in the tablet.
  • Co-administration with dofetilide, fampridine, rifampin or St. John’s wort.

See product monograph and interactions module for further details.

FURTHER INFORMATION

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).

A study is currently underway to find out whether the tablet can be cut or crushed (clinicaltrials.gov/ct2/show/NCT04244448).

For the company, the data is currently insufficient and they recommend against cutting or crushing the tablet and swallowing it whole.

Storage

Store the tablets below 30° C.

REFERENCES

  • Bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), Gilead Sciences, Ontario, Canada, May 21, 2021.
  • Bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), Prescribing Information, Gilead Sciences, California USA, May 2021.
  • Eron JJ, Wilkin A, Ramgopal M, Osiyemi O, McKellar M et al. A Daily Single Tablet Regimen (STR) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Virologically-Suppressed Adults Living with HIV and End Stage Renal Disease on Chronic Hemodialysis. Open Forum Infect Dis. 2020 Oct; 7(1): S529–S530.
  • Spinner C, Stoehr A, Wong A, de Wet J, Zeggagh J et al. Starting or switching to bictegravir/emtricitabine/tenofovir alafenamide in clinical practice: pooled 12-month results from the global BICSTaR study. HIV Glasgow – Virtual, 5-8 October 2020. Abstract P046.
  • Foisy M, Pharm.D., AAHIVP, Northern Alberta Program, Royal Alexandra Hospital Site, Edmonton, C. Hughes, Pharm.D., Northern Alberta Program, KEC Site, Edmonton, Alberta, and A Tseng, Pharm.D, AAHIVP, Toronto General Hospital. ORAL ANTIRETROVIRAL ADMINISTRATION: INFORMATION ON CRUSHING AND LIQUID DRUG FORMULATIONS. May 2020.
  • Fulco PP et al. Crushed bictegravir/emtricitabine/tenofovir alafenamide in a human immunodeficiency virus-positive patient with esophageal cancer. Am J Health Syst Pharm. 2020 Mar 24; 77(7): 509-510.
  • Lozano AB, Chueca N, de Salazar A, Fernández-Fuertes E, Collado A et al. Failure to bictegravir and development of resistance mutations in an antiretroviral-experienced patient. Antiviral Res. 2020 Jul; 179: 104717.

ABBREVIATIONS

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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