Treatment-Naïve Patients
Study 1489: Study Design
BIKTARVY vs ABC/DTG/3TC in treatment-naïve adults1-5
Phase 3, Randomized, Double-Blind, Active-Controlled Study
Study Conducted: November 2015—July 20216
Primary endpoint
Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 (NI margin 12%) using the FDA snapshot algorithm5
Secondary endpoints
Efficacy, safety, and tolerability were assessed through Weeks 96 and 1443,4
Open-label extension
Efficacy in the OLE from Week 144 through Week 240 was calculated using the FDA snapshot algorithm using missing=excluded (M=E) and missing=failure (M=F) analyses1,7
Study 14891,2
Retrospective Analysis of Preexisting Resistance at Baseline in Studies 1489 & 14903,*,†
BIKTARVY Arms From Studies 1489 & 1490 N‡=632 (IN) N‡=634 (PR/RT)
- Participants with preexisting resistance substitutions causing reduced susceptibility to FTC, TAF, ABC, and 3TC were excluded at screening. Retrospective deep sequencing analysis was later attempted on baseline samples from all BIKTARVY-treated participants.
*This list is not inclusive of all RAMs observed in this analysis.3
†BIKTARVY is not indicated for patients with known or suspected substitutions associated with resistance to bictegravir or tenofovir.4
‡Retrospective deep sequencing data were combined with the population sequencing data from screening.
3TC, lamivudine; ABC, abacavir; CD4, cluster of differentiation 4; eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); FTC, emtricitabine, IN, integrase; INSTI, integrase strand transfer inhibitor; IQR, interquartile range; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; PR, protease; RAM, resistance-associated mutation; RT, reverse transcriptase; TAM, thymidine-associated mutation.
References: 1. 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. 2. 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. 3. Acosta RK, Chen GQ, Chang S, et al. Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naïve participants. J Antimicrob Chemother. 2021;76(8):2153-2157. 4. BIKTARVY. Prescribing information. Gilead Sciences, Inc.; 2024.
Study 1489: Efficacy
5 years of durable viral suppression in treatment-naïve adults1-5
BIKTARVY was noninferior to ABC/DTG/3TC at Week 144
Virologic Response in Study 14892-5,8,*
*Percentages do not total 100% due to rounding.
†Treatment difference in HIV-1 RNA <50 copies/mL (95% confidence interval, P value).
Treatment outcomes were similar across subgroups, regardless of age, sex, race, baseline viral load, and baseline CD4+ cell count at Week 1442
Durable viral suppression at Week 2401
In a 96-week open-label extension from Week 144 through Week 240, virologic suppression at each study visit through Week 240 was assessed for adults who were initially randomized to BIKTARVY at Week 01,7:
- Using an M=E analysis, 97.7% (n=213) maintained virologic suppression at Week 240
- Using an M=F analysis, 66.2% (n=314) maintained virologic suppression at Week 240
Virologic suppression was also assessed in participants who switched from ABC/DTG/3TC to BIKTARVY at Week 1447:
- Using an M=E analysis, 99.5% (n=218) maintained virologic suppression at Week 240
- Using an M=F analysis, 85.4% (n=254) maintained virologic suppression at Week 240
In an M=E analysis, participants with missing data are excluded when calculating the proportion of participants with HIV-1 RNA <50 copies/mL. In an M=F analysis, all missing data are treated as treatment failures (HIV-1 RNA ≥50 copies/mL).
Overall rapid and sustained reduction in viral load with BIKTARVY1,3-5,7
Study 1489: Missing=Excluded (M=E) Analysis1,3-5,7
‡M=E data for participants who switched from ABC/DTG/3TC to BIKTARVY.
- In an M=E analysis, participants with missing data are excluded when calculating the proportion of participants with HIV-1 RNA <50 copies/mL
Study 1489: Missing=Failure (M=F) Analysis1,3-5,7
Data is presented from Study Week 0 to Week 240 for participants initially randomized to BIKTARVY. Data for participants who switched to BIKTARVY from ABC/DTG/3TC in the OLE is presented from OLE Week 0 to Week 96.
- Participants who switched from ABC/DTG/3TC had similar rates of virologic suppression (M=F) to participants initially started on BIKTARVY7
- In an M=F analysis, all missing data are treated as treatment failures (HIV-1 RNA ≥50 copies/mL)
Study 1489 Virologic Outcomes1-4,*
*Week 48 window was between Day 295 and 378 (inclusive); Week 96 window was between Day 631 and 714 (inclusive); Week 144 window was between Day 967 and 1050 (inclusive).
†Percentages do not total 100% due to rounding.
‡Includes participants who had ≥50 copies/mL in the Week 48, 96, or 144 window; participants who discontinued early due to lack or loss of efficacy; and participants who discontinued for reasons other than an adverse event (AE), death, or lack or loss of efficacy and at the time of discontinuation had a viral value of ≥50 copies/mL.
§Includes participants who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted in no virologic data on treatment during the specified window.
||Includes participants who discontinued for reasons other than an AE, death, or lack or loss of efficacy; eg, withdrew consent, loss to follow-up, etc.
CI, confidence interval.
References: 1. BIKTARVY. Prescribing information. Gilead Sciences, Inc.; 2024. 2. 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. 3. 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. 4. 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.
IMPORTANT SAFETY INFORMATION
Adverse reactions
- Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).
Study 1490: Study Design
BIKTARVY vs DTG+FTC/TAF in treatment-naïve adults1,2,4,9,10
Phase 3, Randomized, Double-Blind, Active-Controlled Study
Study Conducted: November 2015—July 202111
Primary endpoint
Proportion of adults with HIV-1 RNA <50 copies/mL at Week 48 (NI margin 12%) using the FDA snapshot algorithm10
Secondary endpoints
Efficacy, safety, and tolerability were assessed through Weeks 96 and 1444,9
Open-label extension
Efficacy in the OLE from Week 144 through Week 240 was calculated using the FDA snapshot algorithm using missing=excluded (M=E) and missing=failure (M=F) analyses1,7
Study 14901,2
Retrospective Analysis of Preexisting Resistance at Baseline in Studies 1489 & 14903,*,†,‡
BIKTARVY Arms From Studies 1489 & 1490 N§=632 (IN) N§=634 (PR/RT)
- Participants with preexisting resistance substitutions causing reduced susceptibility to FTC, TAF, ABC, and 3TC were excluded at screening. Retrospective deep sequencing analysis was later attempted on baseline samples from all BIKTARVY-treated participants.
*Percentages do not total 100% due to rounding.
†This list is not inclusive of all RAMs observed in this analysis.3
‡BIKTARVY is not indicated for patients with known or suspected substitutions associated with resistance to bictegravir or tenofovir.4
§Retrospective deep sequencing data were combined with the population sequencing data from screening.
CD4, cluster of differentiation 4; DTG, dolutegravir; eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault); FTC, emtricitabine; IN, integrase; INSTI, integrase strand transfer inhibitor; IQR, interquartile range; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; PR, protease; RAM, resistance-associated mutation; RT, reverse transcriptase; TAF, tenofovir alafenamide; TAM, thymidine-associated mutation.
References: 1. 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. 2. 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. 3. Acosta RK, Chen GQ, Chang S, et al. Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naïve participants. J Antimicrob Chemother. 2021;76(8):2153-2157. 4. BIKTARVY. Prescribing Information. Gilead Sciences, Inc.; 2024.
Study 1490: Efficacy
5 years of durable viral suppression in treatment-naïve adults1,2,4,9,10
BIKTARVY was noninferior to DTG+FTC/TAF at Week 144
Virologic Response in Study 14902,4,8-10,*
*Percentages do not total 100% due to rounding.
†Treatment difference in HIV-1 RNA <50 copies/mL (95% confidence interval, P value).
Treatment outcomes were similar across subgroups, regardless of age, sex, race, baseline viral load, and baseline CD4+ cell count at Week 1442
Durable viral suppression at Week 2401
In a 96-week open-label extension from Week 144 through Week 240, virologic suppression at each study visit through Week 240 was assessed for adults who were initially randomized to BIKTARVY at Week 01,7:
- Using an M=E analysis, 99.5% (n=219) maintained virologic suppression at Week 240
- Using an M=F analysis, 68.1% (n=320) maintained virologic suppression at Week 240
Virologic suppression was also assessed in participants who switched from DTG+FTC/TAF to BIKTARVY at Week 1447:
- Using an M=E analysis, 99.1% (n=234) maintained virologic suppression at Week 240
- Using an M=F analysis, 87.5% (n=265) maintained virologic suppression at Week 240
In an M=E analysis, participants with missing data are excluded when calculating the proportion of participants with HIV-1 RNA <50 copies/mL. In an M=F analysis, all missing data are treated as treatment failures (HIV-1 RNA ≥50 copies/mL).
Overall rapid and sustained reduction in viral load with BIKTARVY1,4,7,9,10
Study 1490: Missing=Excluded (M=E) Analysis1,4,7,9,10
§M=E data for participants who switched from DTG+FTC/TAF to B/F/TAF.
- In an M=E analysis, participants with missing data are excluded when calculating the proportion of participants with HIV-1 RNA <50 copies/mL
Study 1490: Missing=Failure (M=F) Analysis1,4,7,9,10
Data is presented from Study Week 0 to Week 240 for participants initially randomized to BIKTARVY. Data for participants who switched to BIKTARVY from DTG+FTC/TAF in the OLE is presented from OLE Week 0 to Week 96.
- Participants who switched from DTG+FTC/TAF regimens had similar rates of virologic suppression (M=F) to participants initially started on BIKTARVY7
- In an M=F analysis, all missing data are treated as treatment failures (HIV-1 RNA ≥50 copies/mL)
Study 1490 Virologic Outcomes1-4,*
*Week 48 window was between Day 295 and 378 (inclusive); Week 96 window was between Day 631 and 714 (inclusive); Week 144 window was between Day 967 and 1050 (inclusive).
†Includes participants who had ≥50 copies/mL in the Week 48, 96, or 144 window; participants who discontinued early due to lack or loss of efficacy; and participants who discontinued for reasons other than an adverse event (AE), death, or lack or loss of efficacy and at the time of discontinuation had a viral value of ≥50 copies/mL.
‡Includes participants who discontinued due to AE or death at any time point from Day 1 through the time window if this resulted in no virologic data on treatment during the specified window.
§Includes participants who discontinued for reasons other than an AE, death, or lack or loss of efficacy; eg, withdrew consent, loss to follow-up, etc.
CI, confidence interval.
References: 1. BIKTARVY. Prescribing information. Gilead Sciences, Inc.; 2024. 2. 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. 3. 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. 4. 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.
IMPORTANT SAFETY INFORMATION
Adverse reactions
- Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).
Study 1489 and 1490: Post Hoc Pooled Analysis
5 years of powerful viral suppression in treatment-naïve adults with high baseline viral load and low CD4 cell count2,5,10,12
In a post hoc subgroup analysis of pooled data from Studies 1489 and 1490 through Week 240, participants initially randomized to BIKTARVY were stratified by:
- Baseline viral load (BL VL) <100,000, 100,000 to 400,000, and >400,000 copies/mL
- Baseline CD4 < or ≥200 cells/μL
- Baseline viral load ≥100,000 copies/mL and CD4 <200 cells/μL
Post Hoc Pooled Analysis of Studies 1489 and 1490 Using an M=E Analysis12
- In an M=E analysis, participants with missing data are excluded when calculating the proportion of participants with HIV-1 RNA <50 copies/mL.
High rates of virologic suppression were achieved and maintained in all subgroups at 5 years12
Post Hoc Pooled Analysis of Studies 1489 and 1490 Using an M=F Analysis12
Treatment-Naïve Adults with HIV-1 RNA <50 copies/mL, %
- In an M=F analysis, all missing data are treated as treatment failures (HIV-1 RNA ≥50 copies/mL).
Study 1489 and 1490: Resistance
Zero cases of resistance to BIKTARVY through 5 years in treatment-naïve adults1,2,7
Among the treatment-naïve adults who participated in Studies 1489 and 1490, 634 participants received BIKTARVY through Week 144 of the double-blind phase, and 1025 participants received BIKTARVY through Week 96 of the extension phase. Of the 1025 treatment-naïve adults who participated in the OLE, 506 participants continued on BIKTARVY, 254 participants switched from ABC/DTG/3TC, and 265 participants switched from DTG+FTC/TAF at Week 144.1,2,7
In the final resistance analysis population, no amino acid substitutions associated with BIKTARVY resistance emerged in the 11 participants who experienced treatment failure and had evaluable genotypic resistance data.2
BIKTARVY Patient Brochure
The brochure provides information about BIKTARVY and how it can help your patients, whether they are new to treatment or switching from another regimen, reach important HIV health goals like staying undetectable.
Download BIKTARVY Patient Brochure (English) Download BIKTARVY Patient Brochure (Español)3TC, lamivudine; ABC, abacavir; AE, adverse event; CD4, cluster of differentiation 4; DTG, dolutegravir; eGFRCG, estimated glomerular filtration rate (Cockcroft-Gault) FDA; US Food and Drug Administration; FTC, emtricitabine; HBV, hepatitis B virus; HCV, hepatitis C virus; INSTI, integrase strand transfer inhibitor; M=E, missing=excluded; M=F, missing=failure; NI, noninferiority; NRTI, nucleoside reverse transcriptase inhibitor; OLE, open-label extension; QD, once daily; RNA, ribonucleic acid; TAF, tenofovir alafenamide.
References: 1. 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. 2. BIKTARVY. Prescribing information. Gilead Sciences, Inc.; 2024. 3. 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. 4. 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. 5. 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. 6. Study to evaluate the safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus abacavir/dolutegravir/lamivudine in human immunodeficiency virus-1 (HIV-1) infected, antiretroviral treatment-naive adults. ClinicalTrials.gov identifier: NCT02607930. Updated March 2, 2022. Accessed January 6, 2023. https://clinicaltrials.gov/ct2/show/NCT02607930 7. 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. 8. Data on file. Gilead Sciences, Inc. 9. 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. 10. 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. 11. Study to evaluate the safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir + emtricitabine/tenofovir alafenamide in human immunodeficiency virus (HIV-1) infected, and antiretroviral treatment-naive adults. ClinicalTrials.gov identifier: NCT02607956. Updated March 7, 2022. Accessed January 6, 2023. https://clinicaltrials.gov/ct2/show/NCT02607956 12. 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.
