INDICATION

BIKTARVY® is indicated as a complete regimen for the treatment of HIV-1 infection in adult and pediatric patients weighing ≥14 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of BIKTARVY.

Please see below for Important Safety Information for BIKTARVY.

BIKTARVY® Is Backed by Robust Clinical Trial Experience1,2

Extensive clinical trials with over 1500 people of various age groups and ethnicities

Chart Studies.
Chart Studies.

BIKTARVY is being studied in additional clinical trials

  • BRAAVE 2020: The first ongoing clinical trial in 495 Black Americans to study their response to HIV-1 treatment regimens3
  • BICSTaR: Ongoing multicountry, multicenter, prospective observational cohort study aimed to evaluate the effectiveness and safety of treatment with BIKTARVY with a planned total enrollment of 1400 people living with HIV4

IMPORTANT SAFETY INFORMATION

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted.

BIKTARVY is being studied in additional clinical trials

  • BRAAVE 2020: The first BIKTARVY clinical trial in 495 Black Americans to study their response to HIV-1 treatment regimens3
  • BICSTaR: Ongoing multicountry, multicenter, prospective observational cohort study aimed to evaluate the effectiveness and safety of treatment with BIKTARVY with a planned total enrollment of 2000 people living with HIV4

BIKTARVY vs ABC/DTG/3TC in Virologically Suppressed Adults1,5,6

Study 1844: Phase 3, Randomized, Double-Blind, Active-Controlled Study

Study 1844: Phase 3, Randomized, Double-Blind, Active-Controlled Study.
Study 1844: Phase 3, Randomized, Double-Blind, Active-Controlled Study.

Primary endpoint

Proportion of adults with HIV-1 RNA ≥50 copies/mL at Week 48 using the FDA snapshot algorithm

  • Patients were on a stable baseline regimen for at least 3 months and had no history of treatment failure

Open-label extension

The objective of the OLE from Week 48 through Week 168 was to evaluate the efficacy and safety of BIKTARVY after additional exposure

  • Efficacy in the extension phase from Week 48 through Week 168 was calculated using missing=excluded (M=E) analysis
SEE THE DATA

BIKTARVY vs ATV- or DRV-Based Regimen in Virologically Suppressed Adults1,7,8

Study 1878: Phase 3, Randomized, Open-Label, Active-Controlled Study

Study 1878: Phase 3, Randomized, Open-Label, Active-Controlled Study.
Study 1878: Phase 3, Randomized, Open-Label, Active-Controlled Study.

Primary endpoint

Proportion of adults with HIV-1 RNA ≥50 copies/mL at Week 48 using the FDA snapshot algorithm

  • Patients were stably suppressed on baseline regimen for at least 6 months, not previously treated with any INSTI, and had no history of treatment failure

Extension phase

The objective of the extension phase from Week 48 through Week 96 was to evaluate the efficacy and safety of BIKTARVY after additional exposure

  • Efficacy in the extension phase from Week 48 through Week 96 was calculated using missing=excluded (M=E) analysis
SEE THE DATA

BIKTARVY vs an INSTI- or PI-Based Regimen in Virologically Suppressed Adult Women2,9

Study 1961: Phase 3, Randomized, Open-Label, Active-Controlled Study

Study 1961: Phase 3, Randomized, Open-Label, Active-Controlled Study.
Study 1961: Phase 3, Randomized, Open-Label, Active-Controlled Study.

Primary endpoint

Proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 using the FDA snapshot algorithm

  • Patients were on a stable baseline regimen for at least 3 months

Extension phase

The objective of the extension phase from Week 48 through Week ≥96 was to evaluate the efficacy and safety of BIKTARVY after additional exposure

  • At Week 48, the women receiving an INSTI- or PI-based regimen at baseline were switched to BIKTARVY, and an additional analysis was performed at Week 96
  • Efficacy in the extension phase from Week 48 through Week 96 was calculated using missing=excluded (M=E) analysis
SEE THE DATA

BIKTARVY in Virologically Suppressed Adults Aged ≥65 Years11,12

Study 4449: Phase 3b, Open-Label, Single-Arm Study

Study 4449: Phase 3b, Open-Label, Single-Arm Study.
Study 4449: Phase 3b, Open-Label, Single-Arm Study.

Primary endpoints

Proportion of participants with HIV-1 RNA <50 copies/mL at Week 24 using the FDA snapshot algorithm

  • Patients were on a stable baseline regimen for at least 3 months

Secondary endpoints

  • Efficacy at Weeks 48, 72, and 96 using the FDA snapshot algorithm
  • Safety and tolerability through Week 96
SEE THE DATA

BIKTARVY in Virologically Suppressed Children and Adolescents1,13,14

Study 1474: Phase 2/3, Single-Arm, Open-Label, Multi-Cohort Study

Study 1474: Phase 2/3, Single-arm, Open-label, Multicenter Study.
Study 1474: Phase 2/3, Single-arm, Open-label, Multicenter Study.

Primary endpoint

Determination of plasma PK and evaluation of safety and tolerability through Week 24

  • Patients were on a stable baseline regimen for at least 6 months

Secondary endpoints

Proportion of children and adolescents with HIV-1 RNA <50 copies/mL at Week 24 using the FDA snapshot algorithm

  • Efficacy, safety, and tolerability were also evaluated through Week 48 for cohorts 1 & 2

Extension phase (cohorts 1 & 2)

Efficacy in the extension phase from Week 48 to Week 96 was calculated using a missing=excluded (M=E) analysis

  • Safety and tolerability were also evaluated through Week 96
SEE THE DATA

IMPORTANT SAFETY INFORMATION (cont’d)

Contraindications

  • Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

Powerful Efficacy in Virologically Suppressed Adults1,2,5,7,15

≥92% of adults who switched to BIKTARVY maintained virologic suppression at Week 48

Virologic Response in Studies 1844 and 1878

Graphs of 1844 and 1878 studies showing the efficacy data in virologically suppressed adults.
Graphs of 1844 and 1878 studies showing the efficacy data in virologically suppressed adults.

#Difference (95% confidence interval).

#Difference (95% confidence interval).

Study 18446: Durable viral suppression at Week 168

In a 120-week OLE from Week 48 through Week 168, using an M=E analysis:
Virologic suppression was maintained at all 12-week time points from Week 48 to Week 168 in 99% to 100% of participants who stayed on or switched to BIKTARVY.

  • The safety profile of BIKTARVY through the OLE was similar to that in the randomized portion of Study 1844

Study 18788: Durable viral suppression at Week 96

In a 48-week extension phase from Week 48, using an M=E analysis:
Virologic suppression was maintained at all 12-week time points from Week 48 to Week 96 in 99% to 100% of participants who stayed on or switched to BIKTARVY.

  • The safety profile of BIKTARVY through the extension phase was similar to that in the randomized portion of Study 1878

IMPORTANT SAFETY INFORMATION (cont’d)

Adverse reactions

  • Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).
SEE THE STUDY DESIGN

BIKTARVY was also studied in a 48-week phase 3 clinical trial comprising adult women2,10

Virologic Response in Study 1961

Graph of 1961 study showing the efficacy data in virologically suppressed adult women. Graph of 1961 study showing the efficacy data in virologically suppressed adult women.

#Difference (95% confidence interval).

Treatment outcomes between treatment groups were similar across subgroups by age, race, and region at Week 481,2

Study 19612,10: Durable viral suppression at Week 96

In a 48-week extension phase from Week 48, using an M=E analysis:
Virologic suppression was maintained at Week 96 in ≥98% of participants who stayed on or switched to BIKTARVY.

  • The safety profile of BIKTARVY in the extension phase was similar to that in the randomized portion of Study 1961
SEE THE STUDY DESIGN

BIKTARVY was also studied in a 96-week, phase 3 clinical trial comprising adults aged ≥65 years11,12,16

Virologic Response in Study 4449

Graph of 4449 study showing the efficacy data in adults aged ≥65 years. Graph of 4449 study showing the efficacy data in adults aged ≥65 years.
SEE THE STUDY DESIGN

BIKTARVY was also studied in a 48-week phase 3 clinical trial comprising children and adolescents1,13,14

Virologic Response in Study 1474

Graph of 1474 study showing the efficacy data in adolescents and children.
  • High rates of virologic suppression were reported using the FDA snapshot algorithm

In a 48-week extension phase from Week 48 to Week 96 using a missing=excluded (M=E) analysis:
Virologic suppression was maintained in 99% of participants in cohorts 1 & 2 at Week 96.


Results were comparable with those seen in trials in adult populations.

SEE THE STUDY DESIGN

IMPORTANT SAFETY INFORMATION (cont’d)

Contraindications

  • Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

No Treatment-Emergent Resistance Associated With BIKTARVY1,2,5-15**

In five phase 3 clinical trials in virologically suppressed patients ranging from Week 24 through Week 168

Resistance icon with BIKTARVY® (bictegravir, emtricitabine, tenofovir alafenamide). Resistance icon with BIKTARVY® (bictegravir, emtricitabine, tenofovir alafenamide).

Study 1844 through Week 168 and Study 1878 through Week 96

Among 572 virologically suppressed adults randomized to BIKTARVY in Studies 1844 and 1878 through Week 48, 2 participants with virologic rebound had genotypic and phenotypic data (1 for RT, 1 for IN and RT), and no treatment-emergent resistance to BIKTARVY was detected through Week 48.

  • 524 virologically suppressed adults participated in an open-label extension (OLE) of Study 1844. 259 were continuing BIKTARVY and 265 switched to BIKTARVY at Week 48. No treatment-emergent resistance was detected through Week 168, including in the 1 participant who switched to BIKTARVY and met the criteria for resistance testing.
  • 516 virologically suppressed adults participated in an extension phase of Study 1878. 272 were continuing BIKTARVY and 244 switched to BIKTARVY at Week 48. No treatment-emergent resistance was detected through Week 96, including in the 3 participants who switched to BIKTARVY and met the criteria for resistance testing.

Study 1961 and Study 4449 through Week 96

Among 234 virologically suppressed adult women randomized to BIKTARVY in Study 1961 through Week 48, 1 participant met the criteria for resistance testing, and no treatment-emergent resistance to BIKTARVY was detected through Week 48.

  • 459 virologically suppressed adult women participated in an extension phase of Study 1961. 231 were continuing BIKTARVY and 228 switched to BIKTARVY at Week 48. Three participants who switched met the criteria for resistance testing, and no treatment-emergent resistance to BIKTARVY was detected through Week 96.

Among 86 virologically suppressed adults aged ≥65 years in Study 4449 through Week 96, no participants met the criteria for resistance testing, and no treatment-emergent resistance to BIKTARVY was detected through Week 96.

Study 1474 Cohort 1 & 2 through Week 96 and Cohort 3 through Week 24

Among 100 virologically suppressed children and adolescents aged ≥6 to <18 years in Study 1474 in cohorts 1 and 2, 5 participants met the criteria for resistance testing, no treatment-emergent resistance to BIKTARVY was detected through Week 96.

Among 22 virologically suppressed children aged ≥2 in Study 1474 (cohort 3), no participants met the criteria for resistance testing, and no treatment-emergent resistance to BIKTARVY was detected through Week 24.

Please see below for additional Important Safety Information for BIKTARVY.

INDICATION

BIKTARVY® is indicated as a complete regimen for the treatment of HIV-1 infection in adult and pediatric patients weighing ≥14 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of BIKTARVY.

Please see below for Important Safety Information for BIKTARVY.

IMPORTANT SAFETY INFORMATION (cont’d)

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

  • Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted.

Contraindications

  • Coadministration: Do not use BIKTARVY with dofetilide or rifampin.

Warnings and precautions

  • Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions.
  • Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
  • New onset or worsening renal impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)–containing products. Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min except in virologically suppressed adults <15 mL/min who are receiving chronic hemodialysis. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
    Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus.
  • Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse reactions

  • Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).

Drug interactions

  • Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
  • Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1.
  • Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.

Dosage and administration

  • Dosage: Adult and pediatric patients weighing ≥25 kg: 1 tablet containing 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), and 25 mg tenofovir alafenamide (TAF) taken once daily with or without food. Pediatric patients weighing ≥14 kg to <25 kg: 1 tablet containing 30 mg BIC, 120 mg FTC, and 15 mg TAF taken once daily with or without food. For these pediatric patients, who are unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes.
  • Renal impairment: For patients weighing ≥25 kg, not recommended in patients with CrCl 15 to <30 mL/min, or <15 mL/min who are not receiving chronic hemodialysis, or <15 mL/min who are receiving chronic hemodialysis and have no antiretroviral treatment history. For patients weighing ≥14 kg to <25 kg, not recommended in patients with CrCl <30 mL/min.
  • Hepatic impairment: Not recommended in patients with severe hepatic impairment.
  • Prior to or when initiating: Test patients for HBV infection.
  • Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.

Pregnancy and lactation

  • Pregnancy: There is insufficient human data on the use of BIKTARVY during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using BIKTARVY during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population.
  • Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.

*ABC/3TC or FTC/TDF + boosted ATV or DRV regimen (cobicistat or ritonavir).

E/C/F/TAF or E/C/F/TDF or ATV+RTV+FTC/TDF.

Switched from E/C/F/TAF or F/TDF + a third agent.

§Open-label, single-arm trial included virologically suppressed adolescents, aged ≥12 to <18 years weighing at least 35 kg (n=50), virologically suppressed children aged ≥6 to <12 years weighing at least 25 kg (n=50), and virologically suppressed children, aged 2 and up and weighing at least 14 kg (n=22).

||Cobicistat or ritonavir.

Cohort 3 received low-dose BIKTARVY (bictegravir 30 mg, emtricitabine 120 mg, tenofovir alafenamide 25 mg).

**Based on the resistance analysis population.

3TC, lamivudine; ABC, abacavir; ATV, atazanavir; BICSTaR, bictegravir single tablet regimen; C, cobicistat; DRV, darunavir; DTG, dolutegravir; E, elvitegravir; eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); F, emtricitabine; FTC, emtricitabine; IN, integrase, INSTI, integrase strand transfer inhibitor; IQR, interquartile range; NRTI, nucleoside reverse transcriptase inhibitor; OLE, open-label extension; PK, pharmacokinetics; QD, once daily; RNA, ribonucleic acid; RPV, rilpivirine; RT, reverse transcriptase; RTV, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

References: 1. BIKTARVY. Package insert. Gilead Sciences, Inc.; 2021. 2. Kityo C, Hagins D, Koenig E, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed HIV-1 infected women: a randomized, open-label, multicenter, active-controlled, phase 3, noninferiority trial. J Acquir Immune Defic Syndr. 2019;82(3);321-328. 3. Hagins D, Kumar P, Saag M, et al. Switching to bictegravir/emtricitabine/tenofovir Alafenamide in black americans with HIV-1: a randomized phase 3b, multicenter, open-label study. J Acquir Immune Defic Syndr. 2021;88(1):86-95. 4. Mallolas J, Esposito V, Hocqueloux L, et al. Bictegravir/emtricitabine/tenofovir/alafenamide (B/F/TAF) for the treatment of people living with HIV: 12-month effectiveness, persistence, and safety in a multi-country cohort study. Abstract P010. Presented at: British HIV Association Spring Conference 2022; April 20-22, 2022; Manchester, UK. 5. Molina JM, Ward D, Brar I, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e357-e365. 6. Brar I, Ruane P, Ward D, et al. Long-term follow-up after a switch to bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir, abacavir, and lamivudine. Poster presented at: IDWeek; October 21-25, 2020; Virtual. Poster 1028. 7. Daar ES, DeJesus E, Ruane P, et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e347-e356. 8. Rockstroh J, Molina J-M, Post F, et al. Long-term follow-up after a switch to bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) from a boosted protease inhibitor-based regimen. Poster presented at: HIV Drug Therapy Glasgow 2020; October 5-8, 2020; Virtual. Poster P036. 9. Kityo C, Hagins D, Koenig E, et al. Longer-term (96-week) efficacy and safety of switching to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in women. Oral presentation at: International AIDS Society Conference on HIV Science 2019; July 21-24, 2019; Mexico City, Mexico. Abstract MOAB0106. 10. Data on file. Gilead Sciences, Inc. 11. Maggiolo F, Rizzardini G, Molina J-M, et al. Bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people with HIV aged ≥65 years: week 48 results of a phase 3b, open-label trial. Infect Dis Ther. 2021;10(2):775-788. 12. Maggiolo F, Rizzardini G, Molina J-M, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in adults aged 65 years or older: Week 96 results from an international, phase 3b, open-label trial (GS-US-380-4449). Poster presented at: IAS 2021; July 18-21, 2021; Virtual. Poster PEB160. 13. Gaur AH, Cotton MF, Rodriguez CA, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial. Lancet Child Adolesc Health. 2021;5(9):642-651. 14. Natukunda E, Rodriguez CA, McGrath EJ, et al. B/F/TAF in virologically suppressed adolescents and children: two-year outcomes in 6 to <18 year olds and six-month outcomes in toddlers. Abstract presented at: International Workshop on HIV & Pediatrics. July 16-17, 2021; Virtual. Abstract 2. 15. Andreatta K, William M, Martin R, et al. Resistance analyses of bictegravir/emtricitabine/tenofovir alafenamide switch studies. Poster presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2018; Boston, MA. Poster 506. 16. Maggiolo F, Rizzardini G, Molina J-M, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in adults aged ≥65 years: week 72 results from a phase 3b, open-label trial (GS-US-380-4449). Poster presented at: HIV Drug Therapy Glasgow. 2020; October 5-8, 2020; Glasgow, UK. Poster P038.