Biktarvy® (BIC/FTC/TAF)

Use in Baseline NNRTI Resistance

This document is in response to your request for information regarding the use of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide [BIC/FTC/TAF]) in patients with baseline (BL) non-nucleos(t)ide reverse transcriptase inhibitor resistance (NNRTI-R).

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/biktarvy/biktarvy_pi.

Summary

Product Labeling1

BIC/FTC/TAF is indicated as a complete regimen for the treatment of HIV‑1 in adults and pediatric patients weighing ≥14 kg who have no ARV treatment history; or with an ARV treatment history and not virologically suppressed, with no known or suspected substitutions associated with resistance to the INSTI class, FTC, or TFV; or to replace the current ARV regimen in those who are virologically suppressed (HIV‑1 RNA <50 c/mL) on a stable ARV regimen with no known or suspected substitutions associated with resistance to BIC or TFV.

Clinical Data on BIC/FTC/TAF Use With BL NNRTI-R

In a pooled analysis of four studies that was conducted to determine the prevalence of preexisting NNRTI-R and associated risk factors in virologically suppressed participants who were switched to BIC/FTC/TAF, high rates (97–99%) of virologic suppression were observed in participants with BL NNRTI-R at various timepoints across clinical trials.2-5

In a pooled analysis of ARV-naive participants, BIC/FTC/TAF demonstrated non-inferior efficacy to DTG/ABC/3TC (Study 1489) and DTG + FTC/TAF (Study 1490) with 99% (81/82) of participants with preexisting NNRTI-R maintaining virological suppression at Week 144.6

Clinical Data on BIC/FTC/TAF Use With BL NNRTI-R

Pooled Prevalence of Preexisting NNRTI-R Mutations in Virologically Suppressed Participants

A pooled analysis of four studies (Studies 1844, 1878, 4030, and 4580) was conducted to determine the prevalence of preexisting NNRTI-R and associated risk factors in virologically suppressed participants (N=2200) who were switched to BIC/FTC/TAF (Table 1). BIC/FTC/TAF demonstrated non-inferior efficacy (HIV-1 RNA <50 c/mL) at the primary endpoints.5

Table 1. Summary of BIC/FTC/TAF Switch Studies in Virologically Suppressed Participants5

Abbreviations: ATV=atazanavir; DRV=darunavir; INSTI-R=integrase strand transfer inhibitor resistance; MTR=multi-tablet regimen; SBR=stay on BL regimen; STR=single-tablet regimen; TAM=thymidine analog mutations; TDF=tenofovir disoproxil fumarate.

Preexisting NNRTI‑R was present in 22% of participants (448/1995) at BL, of which 14% (289/1995) were documented via proviral genotyping, making NNRTI-R the most frequently observed class of preexisting drug resistance. Participants who switched to BIC/FTC/TAF maintained high rates of virologic suppression regardless of preexisting NNRTI-R, with 99% of participants with NNRTI-R maintaining virologic suppression (HIV‑1 RNA <50 c/mL) at last on-treatment visit.5

A univariate analysis showed that BL NNRTI-R was significantly associated with the presence of BL NRTI-R and PI-R. A multivariate logistic-regression model showed that history of BL NRTI-R, M184V/I, or PI-R; prior PI or raltegravir treatment, age <50 years, and Black race were all independently associated with preexisting NNRTI-R.5

Studies 1844 and 1878 OLE analysis and safety

In Study 1844, 86/88 participants with BL NNRTI-R who received BIC/FTC/TAF for a median duration of 96 weeks had HIV-1 RNA <50 c/mL at their last visit.3 In Study 1878, 127/129 participants with BL NNRTI-R who received BIC/FTC/TAF for a median duration of 108 weeks had HIV-1 RNA <50 c/mL at their last visit.2

A safety analysis was not conducted in the subgroup of participants with NNRTI-R at BL. In Study 1844, the most common all-grade AEs reported in ≥10% of all participants who received ≥1 dose of BIC/FTC/TAF through a median exposure of 96 weeks were URTI, nasopharyngitis, and diarrhea.3 In Study 1878, the most common all-grade AEs reported in ≥10% of all participants who received ≥1 dose of BIC/FTC/TAF through a median exposure of 101 weeks were headache, nasopharyngitis, upper respiratory infection, and diarrhea.7

Study 4030 safety results at Week 488

A safety analysis was not conducted in the subgroup of participants with NNRTI-R at BL. In the overall safety analysis, the most commonly reported (≥10%) AEs in either group were nasopharyngitis, diarrhea, and URTI. Drug-related AEs that occurred in ≥2% in either group were diarrhea and headache. Six participants (2%) in each arm discontinued the study because of AEs.

Study 4580 (BRAAVE) OLE analysis and safety

Preexisting BL NNRTI mutations were detected in 22% (n=101) of participants (K103N/S, n=52 [11%]; rilpivirine-associated [ie, L100I, K101E/P, E138A/G/K/R, V179L, Y181C/I, Y188L, H221Y, F227C, and M230I/L in RT], n=41 [9%]). Virologic suppression was maintained through Week 72 at a rate of 99% in both the overall pooled BIC/FTC/TAF group (486/489) and in participants with preexisting NNRTI-R (100/101).4

A safety analysis was not conducted in the subgroup of participants with NNRTI-R at BL. In the overall safety analysis, switching to BIC/FTC/TAF was well tolerated, and AEs were comparable between the two treatment arms at Week 24.9 All-grade AEs that occurred in ≥5% of participants who received BIC/FTC/TAF at any time (n=493) included URTI, syphilis, headache, pain in extremity, arthralgia, hypertension, and nasopharyngitis. AEs led to 6 study drug discontinuations between BL and Week 24, 3 discontinuations between Weeks 24 and 48, and 3 discontinuations after Week 48.10

Pooled Efficacy and BL Resistance in ARV-Naive Participants

Study design

An integrated viral resistance analysis of two phase 3 BIC/FTC/TAF clinical trials in ARV‑naive participants (Studies 1489 and 1490) was conducted. All participants were screened using HIV-1 genotypic data with PR and RT population sequencing data obtained from the GenoSure MG assay.11,12 Exclusion criteria included FTC or TFV resistance (Studies 1489 and 1490), in addition to ABC or 3TC resistance (Study 1489). Screened participants with mutations conferring resistance to the NRTIs studied (eg, M184V/I, K65R/E/N) were excluded from study participation as well.11

Efficacy results

BIC/FTC/TAF demonstrated non-inferior efficacy (HIV-1 RNA <50 c/mL) to DTG/ABC/3TC (Study 1489) and DTG + FTC/TAF (Study 1490) by FDA Snapshot analysis at the Week 48 primary endpoint and the secondary endpoints at Weeks 96 and 144.13 Preexisting NNRTI‑R (mutation frequency cut-off: ≥15%) was noted in 82 participants who received BIC/FTC/TAF; 99% of these participants were virologically suppressed at Week 144 (Figure 1).6

Figure 1. Studies 1489 and 1490: Virologic Outcomes With BL NNRTI-R at Week 14414

aLast observation carried forward outcome analysis did not include 7 BIC/FTC/TAF-treated participants and 1 DTG/ABC/3TC-treated participant who had no on-treatment, postbaseline HIV-1 RNA data; 1 of these BIC/FTC/TAF-treated participants had a primary PI-associated resistance substitution.

Retrospective next-generation sequencing/deep sequencing techniques were used to analyze low-frequency viral variants in PR, RT, and integrase. Primary NNRTI-R mutations were detected at low frequencies (2–15%) using deep sequencing in an additional 4.2% of participants (53/1270); all participants with BL primary NNRTI-R were virologically suppressed at Week 96.12

Safety results at Week 144

A safety analysis was not conducted in the subgroup of participants with NNRTI-R at BL. The most common all-grade adverse reactions reported in ≥10% of all participants in the BIC/FTC/TAF arms in either study through Week 144 were nausea, diarrhea, URTI, headache, nasopharyngitis, back pain, fatigue, cough, and syphilis. AEs led to study drug discontinuation in no participants in the BIC/FTC/TAF arm in Study 1489 and in 6 participants (2%) in the BIC/FTC/TAF arm in Study 1490, compared with 5 discontinuations (2%) in the DTG/ABC/3TC arm and 6 discontinuations (2%) in the DTG + FTC/TAF arm.13

References

1. Enclosed, Gilead Sciences Inc. BIKTARVY® (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use. US Prescribing Information. Foster City, CA.

2. Andreatta K, Chang S, Delaney M, et al. Long-term Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide After Switch From Boosted Protease Inhibitor-Based Regimens Including in Those With Preexisting Resistance and Viral Blips [Poster PE1/19]. Paper presented at: 18th European AIDS Conference; October 27-30, 2021; London, United Kingdom.

3. 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 1028]. Paper presented at: IDWeek Virtual; 21-25 October, 2020.

4. Andreatta K, D'Antoni ML, Chang S, et al. High efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in Black adults in the United States, including those with pre-existing HIV resistance and suboptimal adherence. J Med Virol. 2024;96(10):e29899.

5. Andreatta K, Acosta R, D'Antoni ML, et al. Prevalence and Risk Factors of Preexisting NNRTI Resistance Among Suppressed PLWH in B/F/TAF Switch Studies [Poster PEB0254]. Paper presented at: AIDS 2020: 23rd International AIDS Conference Virtual; 06-10 July, 2020.

6. 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-naive participants. J Antimicrob Chemother. 2021.

7. Rockstroh JK, Molina JM, 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 P036]. Paper presented at: HIV GLASGOW Drug Therapy Virtual; 05-08 October, 2020; Glasgow, UK.

8. Sax PE, Rockstroh JK, Luetkemeyer AF, et al. Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with Human Immunodeficiency Virus. Clin Infect Dis. 2020:1-9.

9. 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.

10. 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 802]. Paper presented at: 11th International AIDS Society (IAS) Conference on HIV Science Virtual; 18-21 July, 2021.

11. White K, Kulkarni R, Willkom M, et al. Pooled Week 48 Efficacy and Baseline Resistance: B/F/TAF in Treatment-Naive Patients [Poster 532]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); 04-07 March, 2018; Boston, MA.

12. Acosta R, Willkom M, Martin R, et al. Low-Frequency Resistance Variants in ART-Naive Participants Do Not Affect Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Triple Therapy Outcome [Poster MOPEB242]. Paper presented at: 10th IAS Conference on HIV Science (IAS 2019); 21-24 July, 2019; Mexico City, Mexico.

13. Orkin C, DeJesus E, Sax PE, et al. Three-Year Outcomes of the Fixed-Dose Combination Bictegravir, Emtricitabine, and Tenofovir Alafenamide vs Dolutegravir-Containing Regimens for Initial Treatment of HIV-1 Infection: Week 144 Results from Two Randomised, Double-Blind, Multicentre, Phase 3, Non-Inferiority Trials. The Lancet HIV. 2020;7:e389–400.

14. Acosta RK, Chen GQ, Chang S, et al. HIV With Transmitted Drug Resistance Is Durably Suppressed by B/F/TAF at Week 144 [Poster 1903]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 6-10, 2021; Boston, USA.

Abbreviations

3TC=lamivudine
ABC=abacavir
AE=adverse event
ARV=antiretroviral
BIC=bictegravir
BL=baseline
c/mL=copies/mL
DTG=dolutegravir
FTC=emtricitabine
INSTI=integrase strand transfer inhibitor
NNRTI=non-nucleos(t)ide reverse transcriptase inhibitor
NNRTI-R=non‑nucleos(t)ide reverse transcriptase inhibitor resistance
NRTI=nucleos(t)ide reverse transcriptase inhibitor
NRTI-R=nucleos(t)ide reverse transcriptase inhibitor resistance
OLE=open-label extension
PI=protease inhibitor
PI-R=protease inhibitor resistance
PR=protease
RT=reverse transcriptase
TAF=tenofovir alafenamide
TFV=tenofovir
URTI=upper respiratory tract infection

 

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Biktarvy US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/biktarvy/biktarvy_pi.

Follow-Up

For any additional questions, please contact Gilead Medical Information at:

☎1‐866‐MEDI‐GSI (1‐866‐633‐4474) or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

Data Privacy

The Medical Information service at Gilead Sciences may collect, store, and use your personal information to provide a response to your medical request. We may share your information with other Gilead Sciences colleagues to ensure that your request is addressed appropriately. If you report an adverse event or concern about the quality of a Gilead or Kite product, we will need to use the information you have given us in order to meet our regulatory requirements in relation to the safety of our medicines.

It may be necessary for us to share your information with Gilead’s affiliates, business partners, service providers, and regulatory authorities located in countries besides your own. Gilead Sciences has implemented measures to protect the personal information you provide. Please see the Gilead Privacy Statement (www.gilead.com/privacy-statements) for more information about how Gilead handles your personal information and your rights. If you have any further questions about the use of your personal information, please contact privacy@gilead.com.

BIKTARVY, GILEAD, and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2025 Gilead Sciences, Inc.