Adverse Reactions & Discontinuations
Adverse Reactions in Treatment-Naïve Adults
Studies 1489 and 1490: Proven long-term safety and tolerability profile in treatment-naïve adults who received BIKTARVY® through Week 1441,2
(All Grades) Reported in ≥2% of Adults Who Received BIKTARVY*
*Frequencies of ARs are based on all adverse events attributed to trial drugs by the investigator. No ARs of Grade 2 or higher occurred in >1% of participants treated with BIKTARVY.
The majority (84%) of ARs associated with BIKTARVY were Grade 12
Studies 1489 and 1490: Proven long-term safety and tolerability profile through Week 240 in adults initially randomized to BIKTARVY or switched to BIKTARVY at Week 1442-4
Weight change through Week 144
Study 14891,2
In Study 1489, no adults discontinued BIKTARVY due to weight-related AEs through Week 1441,2
- In Study 1489, an AE of weight increase was reported for BIKTARVY (2.9%), ABC/DTG/3TC (4.1%), and weight decrease for BIKTARVY (1.9%), ABC/DTG/3TC (1.6%)1
Study 14901,2
In Study 1490, no adults discontinued BIKTARVY due to weight-related AEs through Week 1441,2
- In Study 1490, an AE of weight increase was reported for BIKTARVY (2.5%), FTC/TAF+DTG (3.1%), and weight decrease for BIKTARVY (0.9%), FTC/TAF+DTG (0.9%)
Weight change through Week 2403,4
Weight Change From Baseline Through Week 2403
Weight Change Through Week 240 for Switch Arms4
Weight Change From Baseline Through Week 2403
- In the OLEs through Week 240, 1 participant initially randomized to BIKTARVY discontinued due to obesity, and 1 participant who switched to BIKTARVY at Week 144 discontinued due to weight increase. Both were considered to be related to the study drug by the investigator3,4
- Median cumulative weight gain from baseline to Week 240, including the OLE, was 6.1 kg for participants initially randomized to BIKTARVY3
- Cumulative median weight changes at Week 240 were numerically similar for all treatment groups4
- At Week 144, significantly lower weight changes were observed in participants treated with DTG/ABC/3TC vs DTG+F/TAF: 3.5 vs 5.0 kg (P = 0.02)4
- In the OLE from Week 144 to Week 240, greater weight changes were observed in participants who switched to BIKTARVY from DTG/ABC/3TC vs those who switched from DTG+F/TAF: 2.4 vs 1.3 kg (P = 0.01)4
*Median cumulative change at Week 192 (no change from Week 192 to 240).
3TC, lamivudine; ABC, abacavir; AE, adverse event; DTG, dolutegravir; FTC, emtricitabine; OLE, open-label extension; TAF, tenofovir alafenamide.
References: 1. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. 2. Data on file. Gilead Sciences, Inc. 3. Wohl DA, Pozniak A, Workowski K, et al. B/F/TAF five-year outcomes in treatment-naïve adults. Poster presented at: Conference on Retroviruses and Opportunistic Infections; February 12-16, 2022; Virtual. Poster 494. 4. Orkin C, Antinori A, Rockstroh J, et al. Outcomes after switching from 144 weeks of blinded DTG/ABC/3TC or DTG+F/TAF to 96 weeks of open-label B/F/TAF. Poster presented at: HIV Glasgow 2022; October 23-26, 2022; Glasgow UK. Poster P088.
Study 1489: Changes in hip BMD through Week 1441
- BMD declines of ≥7% at the total hip were experienced in 1% of BIKTARVY participants and 2% of ABC/DTG/3TC participants at Week 48, in 2% of BIKTARVY participants and 3% of ABC/DTG/3TC participants at Week 96, and in 5% of BIKTARVY participants and 4% of ABC/DTG/3TC participants at Week 1442
– Analysis was conducted in a subset of the study population (n=597)2
In the OLE:
- A mean change of −0.3% was observed from baseline at Week 240 (n=197)3
- BMD declines of ≥7% at the total hip were experienced in 8% of participants (n=15/197) at Week 2402,3
- Includes only participants initially randomized to BIKTARVY at Week 0, as these participants took BIKTARVY for 240 weeks3
The long-term clinical significance of changes in BMD is not known.
- BMD was assessed at baseline, Week 24, Week 48, Week 96, Week 144, Week 192, and Week 240 by dual-energy x-ray absorptiometry (DXA) scans2,3
Study 1489: Changes in lumbar spine BMD through Week 1441
- BMD declines of ≥5% at the lumbar spine were experienced in 10% of BIKTARVY participants and 6% of ABC/DTG/3TC participants at Week 48, in 12% of BIKTARVY participants and 6% of ABC/DTG/3TC participants at Week 96, and in 12% of BIKTARVY participants and 8% of ABC/DTG/3TC participants at Week 1442
– Analysis was conducted in a subset of the study population (n=603)2
In the OLE:
- A mean change of −0.2% was observed from baseline at Week 240 (n=201)3
- BMD declines of ≥5% at the lumbar spine were experienced in 20% of participants (n=41/201) at Week 2402,3
- Includes only participants initially randomized to BIKTARVY at Week 0, as these participants took BIKTARVY for 240 weeks3
The long-term clinical significance of changes in BMD is not known.
- BMD was assessed at baseline, Week 24, Week 48, Week 96, Week 144, Week 192, and Week 240 by dual-energy x-ray absorptiometry (DXA) scans2,3
BMD was measured only in Study 1489
BMD, bone mineral density; CI, confidence interval; FTC, emtricitabine; OLE, open-label extension.
References: 1. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. 2. Data on file. Gilead Sciences, Inc. 3. Wohl DA, Pozniak A, Workowski K, et al. B/F/TAF five-year outcomes in treatment-naïve adults. Poster presented at: Conference on Retroviruses and Opportunistic Infections; February 12-16, 2022; Virtual. Poster 494.
Changes in eGFRCG and serum creatinine through Week 144
Study 14891-3
- Median serum creatinine increased by 0.1 mg/dL in the BIKTARVY arm and by 0.11 mg/dL in the ABC/DTG/3TC arm from baseline1
In the OLE for Study 1489 in participants who were initially randomized to BIKTARVY at Week 0 and continued through Week 240:
- A median eGFR change of −8.2 mL/min from baseline was observed at Week 240 (n=213)4,5
- Median serum creatinine increased by 0.11 mg/dL in participants from baseline through Week 2405
In participants who switched from ABC/DTG/3TC to BIKTARVY at Week 144 through Week 240:
- A median eGFR change of +2.0 mL/min from Week 144 was observed at Week 240 (n=217)6
The long-term clinical significance of changes in eGFR is not known.
Study 14901,7,8
- Median serum creatinine increased by 0.11 mg/dL in the BIKTARVY arm and by 0.12 mg/dL in the FTC/TAF+DTG arm from baseline1
In the OLE for Study 1490 in participants who were initially randomized to BIKTARVY at Week 0 and continued through Week 240:
- A median eGFR change of -8.5 mL/min from baseline was observed at Week 240 (n=217)4,5
- Median serum creatinine increased by 0.11 mg/dL in patients from baseline through Week 2405
In participants who switched from FTC/TAF+DTG to BIKTARVY at Week 144 through Week 240:
- A median eGFR change of +1.3 mL/min from Week 144 was observed at Week 240 (n=233)6
The long-term clinical significance of changes in eGFR is not known.
3TC, lamivudine; ABC, abacavir; DTG, dolutegravir; eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); FTC, emtricitabine; OLE, open-label extension; TAF, tenofovir alafenamide.
References: 1. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. 2. Wohl DA, Yazdanpanah Y, Baumgarten A, et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e355-e363. 3. Gallant J, Lazzarin A, Mills A, et al. 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. Lancet. 2017;390(10107):2063-2072. 4. Wohl DA, Pozniak A, Workowski K, et al. B/F/TAF five-year outcomes in treatment-naïve adults. Poster presented at: Conference on Retroviruses and Opportunistic Infections; February 12-16, 2022; Virtual. Poster 494. 5. Data on file. Gilead Sciences, Inc. 6. Orkin C, Antinori A, Rockstroh J, et al. Outcomes after switching from 144 weeks of blinded DTG/ABC/3TC or DTG+F/TAF to 96 weeks of open-label B/F/TAF. Poster presented at: HIV Glasgow 2022; October 23-26, 2022; Glasgow UK. Poster P088. 7. Sax PE, Pozniak A, Montes ML, et al. 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. Lancet. 2017;390(10107):2073-2082. 8. Stellbrink H-J, Arribas JR, Stephens JL, et al. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e364-e372.
Median change in fasting lipids from baseline through Week 144
*Except for triglycerides, which are (n=255) at Week 144.
In the OLE for Study 1489:
- In participants who were initially randomized to BIKTARVY at Week 0 and continued through Week 240, median changes in fasting lipids from baseline were as follows (n=202): Total-C: +20 mg/dL, LDL-C: +22 mg/dL, HDL-C: +5 mg/dL, Triglycerides: +11 mg/dL, Total-C:HDL-C ratio: 0.02
- In participants who switched from ABC/DTG/3TC to BIKTARVY at Week 144 through Week 240, median changes in fasting lipids from baseline were as follows (n=215)†: Total-C: +7 mg/dL, LDL-C: +2 mg/dL, HDL-C: 0.0 mg/dL, Triglycerides: -3 mg/dL, Total-C:HDL-C ratio: +0.12
†Except for triglycerides, which are (n=213) at Week 240.
In the OLE for Study 1490:
- In participants who were initially randomized to BIKTARVY at Week 0 and continued through Week 240, median changes in fasting lipids from baseline were as follows (n=208): Total-C: +22 mg/dL, LDL-C: +17 mg/dL, HDL-C: +4 mg/dL, Triglycerides: +10 mg/dL, Total-C:HDL-C ratio: +0.12
- In participants who switched from FTC/TAF+DTG to BIKTARVY at Week 144 through Week 240, median changes in fasting lipids from baseline were as follows (n=225): Total-C: +5 mg/dL, LDL-C: -2 mg/dL, HDL-C: +1 mg/dL, Triglycerides: +2 mg/dL, Total-C:HDL-C ratio: -0.12
Lab abnormalities were observed with both BIKTARVY and comparators through Week 144
Lab abnormalities through Week 240
‡Lipase test performed only in subjects with serum amylase > 1.5 x ULN.
BIKTARVY is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). For patients weighing ≥25 kg, BIKTARVY is not recommended in patients with severe renal impairment (estimated CrCl <30 mL/min) except in virologically suppressed patients with CrCl <15 mL/min on chronic hemodialysis. BIKTARVY is not recommended for patients weighing ≥14 kg with CrCl <30 mL/min.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CrCl, creatinine clearance; GGT, gamma-glutamyl transferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; OLE, open-label extension; ULN, upper limit of normal.
References: 1. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. 2. Data on file. Gilead Sciences, Inc. 3. BIKTARVY. Prescribing information. Gilead Sciences, Inc.; 2022. 4. Orkin C, Antinori A, Rockstroh J, et al. Outcomes after switching from 144 weeks of blinded DTG/ABC/3TC or DTG+F/TAF to 96 weeks of open-label B/F/TAF. Poster presented at: HIV Glasgow 2022; October 23-26, 2022; Glasgow UK. Poster P088.
Studies 1489 and 1490: Proven long-term safety and tolerability profile in a post hoc analysis of participants with high baseline viral load and low CD4 cell count through Week 2405
- 5 cases of IRIS were reported: all had BL VL <100,000 copies/mL, 2 had CD4 <200 cells/µL, and all occurred within the first 48 weeks and resolved with treatment5
- The most common study drug-related AEs were nausea, headache, and diarrhea; there were no drug-related serious adverse events in the high viral load or low CD4 subgroups5
Adverse Reactions in Virologically Suppressed Participants
Studies 1844 and 1878: Proven safety and tolerability profile in virologically suppressed adults through Week 486-8
DRV-based
Regimen (n=287)
†Frequencies of ARs are based on all adverse events attributed to trial drugs by the investigator. No ARs of Grade 2 or higher occurred in >1% of participants treated with BIKTARVY.2
- The majority of ARs associated with BIKTARVY were Grade 1 in Study 1844 (58%) and in Study 1878 (76%)2
- The safety profile of BIKTARVY in the extension phases through Week 96 and Week 168 was similar to that in the randomized phases of Studies 1878 and 1844, respectively9,10
-
Overall, the safety profile of BIKTARVY in virologically suppressed adults was similar to that in treatment-naïve adults8
- The most common ARs (incidence ≥5%; all grades) in clinical trials of treatment-naïve adults who received BIKTARVY were diarrhea, nausea, and headache8
Weight change through Week 481
Weight change through Week 1201,†,‡
In Study 1844, no adults discontinued BIKTARVY due to weight-related adverse events through Week 1681,2
- In participants who continued on or switched to BIKTARVY during OLE, changes from baseline in body weight were consistent with changes reported through Week 481
*Shown for reference.
†Low participant numbers out to Week 168 (n=12); median change at Week 168: +2.1 kg.
‡This analysis includes participants initially randomized to BIKTARVY and participants who switched to BIKTARVY during the OLE.
3TC, lamivudine; ABC, abacavir; DTG, dolutegravir; IQR, interquartile range; OLE, open-label extension.
References: 1. 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. 2. Molina J-M, 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.
Weight change through Week 481,2
Weight change through Week 961,*
In Study 1878, no adults discontinued BIKTARVY due to weight-related adverse events through Week 961,3
- In participants who continued on or switched to BIKTARVY during the extension phase, changes from baseline in body weight were consistent with changes reported through Week 481
*This analysis includes participants initially randomized to BIKTARVY and participants who switched to BIKTARVY during the extension phase.
IQR, interquartile range; SBR, stayed on baseline regimen.
References: 1. 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. 2. Data on file. Gilead Sciences, Inc. 3. 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.
Study 1961: Proven safety and tolerability profile in virologically suppressed adult women through Week 482,11
Through Week 48, no woman discontinued due to AEs in either treatment arm11
- The safety profile of BIKTARVY in the extension phase through Week 96 was similar to that in the randomized phase of Study 196112
Study 4449: Proven safety and tolerability profile in virologically suppressed adults aged ≥65 years through Week 962,13,14
‡ Frequencies of ARs are based on all adverse events attributed to trial drugs by the investigator.
Through Week 96, there were 2 (2.3%) Grade 3 study drug-related AEs in adults aged ≥65 years14
Study 1474: Proven safety and tolerability profile in virologically suppressed children and adolescents2,15-17
The other ARs that occurred in single participants were similar to those seen in adults.8,16,17
BRAAVE: Proven safety and tolerability profile in virologically suppressed Black American Adults through Week 722,18
- The most common ARs reported (all grades) in ≥1% of participants on BIKTARVY through Week 48 (n=493) were weight increase (2%), flatulence (1%), abnormal dreams (1%), diarrhea (1%), headache (1%)2
- The most common ARs in the extension through Week 72 were similar to those observed in participants who received BIKTARVY through Week 482
Weight change from baseline through Week 721-3
Weight Change Through Week 24
Weight Change Through Week 72
Weight changes through Week 24 were similar between adults who were randomized to BIKTARVY and those who stayed on baseline regimen1-3
In BRAAVE, no adults discontinued due to weight-related adverse events through Week 723
*From 2-sided Wilcoxon rank-sum test comparing BIKTARVY vs SBR at Week 24.
SBR, stayed on baseline regimen.
References: 1. 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. 2. Hagins DP, Kumar PN, Saag M, et al. Randomized switch to B/F/TAF in African American adults with HIV. Abstract presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston, MA. Abstract 36. 3. Kumar P, Stephens JL, Wurapa AK, et al. Week 72 outcomes and Covid-19 impact from the BRAAVE 2020 study: a randomized switch to B/F/TAF in Black American adults with HIV. Poster presented at: International AIDS Society Conference on HIV Science; July 18-21, 2021; Virtual. Poster PEB161.
Weight changes through Week 721
SBR vs BIKTARVY
Delayed Switch*
More weight gain was observed at Week 72 in participants switching from TDF- or ABC-based regimens compared with those remaining on a TAF-based regimen1
*Baseline for delayed switch: time of first BIKTARVY dose.
†From 2-sided Wilcoxon rank-sum test comparing baseline regimens containing TAF vs TDF.
‡Comparing baseline regimens containing TAF vs ABC.
ABC, abacavir; NRTI, nucleoside reverse transcriptase inhibitor; SBR, stayed on baseline regimen; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
Reference: 1. Kumar P, Stephens JL, Wurapa AK, et al. Week 72 outcomes and Covid-19 impact from the BRAAVE 2020 study: a randomized switch to B/F/TAF in Black American adults with HIV. Poster presented at: International AIDS Society Conference on HIV Science; July 18-21, 2021; Virtual. Poster PEB161.
Discontinuations In Treatment-Naïve Adults
Low rates of discontinuation due to adverse events in treatment-naïve adults1-4
Treatment-Naïve Adults
Through Week 1441
Study 1489
(n=314)
(n=315)
Study 1490
(n=320)
(n=325)
Through Week 240 (including OLE)
in participants initially randomized to BIKTARVY3
Study 1489
(n=314)
Study 1490
(n=320)
In participants who switched to BIKTARVY
at Week 144 through Week 2404
Study 1489
(n=254)
Study 1490
(n=265)
No treatment-naïve adults discontinued BIKTARVY due to renal-, hepatic-, or bone-related adverse events through Week 2401,3,4
- Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus.8
- BIKTARVY is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). For patients weighing ≥25 kg, BIKTARVY is not recommended in patients with severe renal impairment (estimated CrCl <30 mL/min) except in virologically suppressed patients with CrCl <15 mL/min on chronic hemodialysis. BIKTARVY is not recommended for patients weighing ≥14 kg with CrCl <30 mL/min.8
Discontinuations In Virologically Suppressed Participants
Low rates of discontinuation due to adverse events in virologically suppressed participants2,6-19
Virologically Suppressed Adults
Through Week 482,6,7
Study 1844
(n=282)
(n=281)
Study 1878
(n=290)
(n=287)
Through Week 168
(including OLE)9
Study 1844
(n=547)
Through Week 96 (including Extension)10
Study 1878
(n=345)
Virologically Suppressed Adult Women
Through Week 4811
Study 1961
0.0%
BIKTARVY
(n=234)
0.0%
INSTI- or PI-based Regimen
(n=236)
Study 1961
(n=234)
(n=236)
Through Week 96 (including Extension)12
Study 1961
0.2%
BIKTARVY
(n=462)
Study 1961
(n=462)
Virologically Suppressed Adults Aged ≥65 Years
Through Week 9614
Study 4449
5.8%
BIKTARVY
(n=86)
Study 4449
(n=86)
Virologically Suppressed Children and Adolescents
Cohorts 1 & 2 Through Week 9615,16
Study 1474
0.0%
Aged ≥12 to <18 years, ≥35 kg Cohort 1 (n=50)
2.0%
Aged ≥6 to <12 years, ≥25 kg Cohort 2 (n=50)
Study 1474
Cohort 3 Through Week 4817
Study 1474
0.0%
Aged ≥2 years, ≥14 kg to <25 kg Cohort 3 (n=22)
Study 1474
Virologically Suppressed Black Americans
Through Week 2419
BRAAVE
(n=330)
(n=165)
Through Week 72 (including Extension)18
BRAAVE
(n=493)
No virologically suppressed participants discontinued BIKTARVY due to bone-related adverse events at any clinical trial time points2,6-19
- In Study 1961, 1 discontinuation occurred due to a hepatic-related adverse event found to be related to study drug2,12
- In BRAAVE, 1 discontinuation occurred due to a renal-related adverse event, which was not reported to be related to study drug18
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.8
3TC, lamivudine; ABC, abacavir; AE, adverse event; ATV, atazanavir; BL, baseline; CD4, cluster of differentiation 4; CrCl, creatinine clearance; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; IRIS, immune reconstitution inflammatory syndrome; PI, protease inhibitor; SAE, serious AE; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; VL, viral load.
References: 1. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. 2. Data on file. Gilead Sciences, Inc. 3. Wohl DA, Pozniak A, Workowski K, et al. B/F/TAF five-year outcomes in treatment-naïve adults. Poster presented at: Conference on Retroviruses and Opportunistic Infections; February 12-16, 2022; Virtual. Poster 494. 4. Orkin C, Antinori A, Rockstroh J, et al. Outcomes after switching from 144 weeks of blinded DTG/ABC/3TC or DTG+F/TAF to 96 weeks of open-label B/F/TAF. Poster presented at: HIV Glasgow 2022; October 23-26, 2022; Glasgow UK. Poster P088. 5. Ramgopal M, Wurapa A, Baumgarten A, et al. 5-year outcomes of bictegravir/emtricitabine/tenofovir alafenamide as initial treatment of HIV-1 in adults with high baseline HIV-1 RNA and/or low CD4 count in two phase 3 randomized clinical trials. Presented at: Infectious Disease Week 2022; October 19-23, 2022; Washington, DC. Poster 1251. 6. Molina J-M, 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. 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. BIKTARVY. Prescribing information. Gilead Sciences, Inc.; 2022. 9. 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. 10. 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. 11. 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. 12. 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. 13. 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. 14. Maggiolo F, Rizzardini G, Molina J-M, et al. Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open- label, switch trial in virologically suppressed people ≥65 years of age. HIV Med. 2023;24(1):27-36. 15. 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. 16. 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. 17. Rodriguez CA. Renate S. Chokephaibulkit K, et al. One year outcome of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed children ≥ 2 years weighing 14 to < 25 kg. 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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.
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.
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 reaction (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.
Please see full Prescribing Information for BIKTARVY® and DESCOVY®, including BOXED WARNINGS.