Biktarvy® (BIC/FTC/TAF)

Use in Baseline M184V/I Resistance

This document is in response to your request for information regarding Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide [BIC/FTC/TAF]) and its use in people with HIV (PWH) with baseline M184V/I resistance mutations.

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 infection in adults and pediatric patients weighing ≥14 kg with no ARV treatment history; or with an ARV treatment history and not VS, 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 VS (HIV-1 RNA <50 c/mL) on a stable ARV regimen with no known or suspected substitutions associated with resistance to BIC or TFV.

HIV-1 isolates with reduced susceptibility to FTC were selected in cell culture and in participants treated with FTC. Reduced susceptibility to FTC was associated with M184V or I substitutions in HIV-1 RT.

Cross-resistance has been observed among NRTIs. FTC-resistant viruses with an M184V/I substitution in HIV-1 RT were cross-resistant to 3TC.

Clinical Data on BIC/FTC/TAF Use in Participants With Baseline M184V/I Mutations

In a pooled analysis of participants in Studies 4030, 4580, 1844, 1878, 4449, and 1474, participants with baseline M184V/I maintained high rates (97–100%) of virologic suppression (HIV-1 RNA <50 c/mL) with BIC/FTC/TAF treatment.2

In an analysis of ARV-naive participants with low-frequency variants in the phase 3 Studies 1489 and 1490, all 6 participants on BIC/FTC/TAF with baseline M184V/I at a 2% to 15% frequency achieved virologic suppression (HIV-1 RNA <50 c/mL) at 96 weeks.3

Real-World Data on BIC/FTC/TAF Use in PWH With Baseline M184V/I Mutations

Real-world studies summarizing outcomes of PWH with baseline M184V/I mutations treated with BIC/FTC/TAF are summarized below.4-8

Clinical Data on BIC/FTC/TAF Use in Participants With Baseline M184V/I Mutations

Pooled Analysis: M184V/I in VS Participants2

Study design and baseline resistance

A pooled analysis was conducted in participants (N=2034) from Studies 4030, 4580 (BRAAVE 2020), 1844, 1878, 4449, and 1474 to evaluate the prevalence of preexisting M184V/I resistance mutation and its effect on virologic outcomes in VS (ie, HIV‑1 RNA <50 c/mL for 3 or 6 months) participants who switched to BIC/FTC/TAF. In Studies 4030 and 4580, participants with baseline M184V/I mutations were allowed, but other studies included in the analysis excluded participants if an M184V/I mutation was detected prior to the switch in therapy. Historical genotype reports were collected during enrollment, if available, and HIV-1 proviral DNA genotype testing was conducted retrospectively on any available baseline samples.

Across all six studies in the pooled analysis, 10% of participants with PR/RT data had preexisting M184V/I (182/1825; Table 1). Most M184V/I mutations were identified by baseline proviral DNA genotyping (167/182; 92%). Eighty-one percent of participants with M184V/I mutations (147/182) had ≥1 other resistance substitution.

Table 1. Pooled Analysis: Frequency of Baseline M184V/I in Participants Treated
With BIC/FTC/TAF2

Efficacy results

High rates (97–100%; M=E analyses) of virologic suppression (HIV‑1 RNA <50 c/mL) were maintained up to 180 weeks after switching to BIC/FTC/TAF, and no treatment-emergent resistance was detected. In participants with preexisting M184V/I who received BIC/FTC/TAF (median duration, 69 weeks), rates of virologic suppression were high
(Figure 1). Rates of virologic suppression were similar between participants with and without M184V/I resistance mutations (98% vs 99%, respectively; P=0.48).

Figure 1. Pooled Analysis: Virologic Suppression by Preexisting M184V/I in the Pooled BIC/FTC/TAF Group (LOCF)2

Abbreviations: BL=baseline; INSTI-R=integrase strand transfer inhibitor resistance; NNRTI-R=non-nucleos(t)ide reverse transcriptase inhibitor resistance; PI-R=protease inhibitor resistance; WT=wild-type allele.

Safety outcomes were not provided for this pooled analysis. Please see product labeling for BIC/FTC/TAF safety information.

Low-Frequency M184V/I in ARV‑Naive Participants3

Study design and baseline resistance

An analysis of participants in the phase 3 Studies 1489 and 1490 was conducted to assess the impact of low-frequency variants on treatment outcomes of ARV-naive participants treated with BIC/FTC/TAF, DTG/ABC/3TC, or DTG + FTC/TAF. All participants were screened using HIV-1 genotype data, with PR and RT population sequencing data obtained from the GenoSure MG assay; a report showing sensitivity to FTC and TAF was required, and participants with M184V/I or K65R were excluded. After enrollment, a retrospective deep sequencing analysis of PR, RT, and integrase was conducted using the deepType HIV assay, and results were compared to population sequencing. Virologic outcomes were assessed at Week 96 using the LOCF method.

Results

In the overall population, high rates (97–98%) of virologic suppression (HIV-1 RNA <50 c/mL) were achieved at Week 96 across all treatment arms, regardless of baseline resistance. Primary NRTI-R substitutions occurred in 26/1274 participants (2%) at baseline per population sequencing methods. Using deep sequencing analysis (2–15% cutoff), 47/1270 participants (3.7%) had low-frequency primary NRTI-R substitutions at baseline; of these, 11 had M184V/I (BIC/FTC/TAF, 6/632 [0.9%]; DTG/ABC/3TC, 4/314 [1.3%]; DTG + FTC/TAF, 1/324 [0.3%]). All 11 participants were VS (HIV RNA <50 c/mL) at Week 96. Safety data were not reported in this subgroup analysis.

Real-World Data on BIC/FTC/TAF Use in PWH With Baseline M184V/I Mutations

Table 2 summarizes real-world studies that report outcomes in PWH with baseline M184V/I resistance who received BIC/FTC/TAF.

Table 2. Real-World Data on PWH With Baseline M184V/I Resistance Who Received BIC/FTC/TAF4-8

Abbreviations: AE=adverse event; BICSTaR=BIC Single Tablet Regimen; DRV=darunavir; PRM=primary resistance mutation; RAM=resistance-associated mutation; TAM=thymidine analog mutation.

References

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

2. Sax PE, Andreatta K, Molina JM, et al. High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I. AIDS. 2022;36(11):1511-1520.

3. 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; July 21-24, 2019; Mexico City, Mexico.

4. Lamaizon C, Cecchini D, Bottaro E, et al. Effectiveness of bictegravir / emtricitabine/tenofovir alafenamide fixed-dose combination in experienced people living with HIV with a history of virologic failure, M184V /I, and other resistance-associated mutations in clinical practice [Poster PN097]. Paper presented at: 25th International AIDS Conference; July 22-26, 2024; Munich, Germany.

5. Lamaizon C, Cecchini D, Brizuela M, et al. Impact of Nucleoside Reverse Transcriptase Inhibitor Resistance-Associated Mutations on Long-Term Virologic Suppression of Bictegravir/Emtricitabine/Tenofovir Alafenamide: Real-World Evidence [Poster]. Paper presented at: 20th European AIDS Conference; October 15-18, 2025; Paris, France.

6. Trottier B, Bonnet F, García-Deltoro MG, et al. Real World Effectiveness and Tolerability of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Treatment Experienced People With HIV and a History of Antiretroviral Drug Resistance Mutations [Poster 1628848]. Paper presented at: ID Week 2023; October 11-15, 2023; Boston, MA.

7. Sheridan R, Osei-Kuffour Ekert Y, Campbell L, et al. Virological outcomes with Bictegravir/Emtricitabine/Tenofovir alafenamide (B/F/TAF) in people previously treated with darunavir-based antiretroviral therapy. HIV Med. 2026;27(5):803-808.

8. Rolle CP, D'Antoni ML, Corales R, et al. Effectiveness of B/F/TAF in adults with HIV who are viremic with M184V/I. AIDS Res Ther. 2025;22(1):126.

Abbreviations

3TC=lamivudine
ABC=abacavir
ARV=antiretroviral
BIC=bictegravir
c/mL=copies/mL
DTG=dolutegravir
FTC=emtricitabine
INSTI=integrase strand transfer inhibitor
LOCF=last observation carried forward
M=E=missing=excluded
NRTI=nucleos(t)ide reverse transcriptase inhibitor
NRTI-R=nucleos(t)ide reverse transcriptase inhibitor resistance
PR=protease
PWH=people with HIV
RT=reverse transcriptase
TAF=tenofovir alafenamide
TFV=tenofovir
VS=virologically suppressed

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.

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