Biktarvy® (BIC/FTC/TAF)

Use in Severe Renal Impairment and Hemodialysis

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 severe renal impairment, including hemodialysis (HD).

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 not recommended in individuals with severe renal impairment (estimated CrCl of 15 to <30 mL/min); or ESRD (estimated CrCl <15 mL/min) who are not receiving chronic HD; or no ARV treatment history and ESRD who are receiving chronic HD.

Clinical Data on BIC/FTC/TAF Use in Severe Renal Impairment and HD

Eligible participants with an eGFR <15 mL/min on HD were permitted to switch from E/C/F/TAF to BIC/FTC/TAF in the OLE period of a phase 3b study (Study 1825)2,3:

• All participants who switched to BIC/FTC/TAF (n=10) maintained HIV‑1 RNA <50 c/mL at Week 48 (M=E analysis). Most AEs were Grade 1 or 2 in severity.
• Mean BIC Ctrough levels were lower in participants on HD than historical mean values of PWH with normal kidney function or mild or moderate kidney impairment, but Ctrough levels of BIC were 4- to 7-fold higher than the paEC95 against wild-type HIV-1 virus for BIC.

In a phase 1 study, BIC AUC∞ was approximately 27% lower in participants with an eGFR of 15 to 29 mL/min than in healthy volunteers with normal renal function. No correlation was observed between the AUC∞ or Cmax and eGFRCG. Overall, BIC was well tolerated.4

In a case series of 6 patients on HD who switched to BIC/FTC/TAF-containing regimens, all patients achieved or maintained virologic suppression, and no patients reported AEs.5

Clinical Data on BIC/FTC/TAF Use in Severe Renal Impairment and HD

Study GS-US-292-1825: BIC/FTC/TAF in PWH With ESRD on Chronic HD

Study design and demographics

A phase 3b, open-label, multicenter, single-arm study was conducted to evaluate the safety, tolerability, PK, and efficacy of E/C/F/TAF in virologically suppressed (HIV-1 RNA <50 c/mL on a stable ARV regimen for ≥6 consecutive months) PWH with ESRD (eGFR <15 mL/min) on chronic HD for ≥6 months. Participants switched from their current ARV regimen to E/C/F/TAF, administered as one tablet once daily, and received treatment for ≥96 weeks. Following regulatory approval of BIC/FTC/TAF by the FDA, the study protocol was amended to allow eligible US participants to switch to BIC/FTC/TAF in the OLE phase for 48 weeks (N=10).2

During the OLE, BIC/FTC/TAF safety was assessed by AEs and laboratory abnormalities; efficacy was assessed by the proportion of participants who were virologically suppressed (HIV‑1 RNA <50 c/mL) according to M=E analysis, and PK sampling was conducted at Weeks 4, 24, and 48.2

The median (range) age of participants who switched to BIC/FTC/TAF was 55 (34–63) years. The median (IQR) eGFRCG at BIC/FTC/TAF start was 11.6 (6.8–17.3) mL/min, and the median (range) duration of time on HD was 4 (2–16) years.3

Virologic outcomes at Week 482

Virologic suppression (HIV-1 RNA <50 c/mL) was maintained in all 10 participants (100%; 95% CI: 69.2–‍100%) according to M=E analysis, with a median (range) duration of BIC/FTC/TAF exposure of 48 (47–52) weeks. The median (range) change in CD4 count and percentage from baseline to Week 48 (n=9) was ‑121 (‑296 to -45) cells/mcL and 1.5% (‑5.2 to 8.8%), respectively. From baseline to Week 48, the median (range) treatment adherence was 88.5% (76.1–99.1%).

PK results at Week 482

Mean BIC Ctrough values at Weeks 4, 24, and 48 are presented in Table 1. Ctrough levels of BIC were lower in participants on HD than the historical mean (%CV) level of 2610 ng/mL (35.2%) in PWH with normal kidney function or mild or moderate kidney impairment. Ctrough levels of BIC stayed 4- to 7‑fold higher than the paEC95 (162 ng/mL) against wild‑type HIV-1 virus for BIC.

Table 1. Study 1825: Mean BIC Ctrough Values at Weeks 4, 24, and 482

Safety results at Week 482,3

All participants had ≥1 AE during the OLE phase, and most AEs were Grade 1 or 2 in severity (Table 2). One participant had >1 Grade 3 AEs, and 3 participants had SAEs; none were considered related to BIC/FTC/TAF. No AEs led to BIC/FTC/TAF discontinuation, and no deaths were reported. Five participants (50%) had ≥1 Grade 3 or 4 laboratory abnormality.

Table 2. Study 1825: AEs and Laboratory Abnormalities (Safety Analysis Set)2,3

aOne participant reported multiple Grade 3 AEs that were not considered treatment related, including congestive cardiac failure, abdominal wall hematoma, pneumonia, respiratory syncytial viral pneumonia, vascular access site hemorrhage, cervical spinal stenosis, spinal stenosis, hypertensive emergency, and hypertensive urgency.

bOne participant reported nausea (Grade 2) and malaise (Grade 1).

cNone were considered treatment related. SAEs consisted of tendon rupture, hyperkalemia, and dyspnea (n=1); angina pectoris, acute myocardial infarction, and skin ulcer (n=1); and vascular access site hemorrhage, pneumonia, respiratory syncytial viral pneumonia, hypertensive urgency, abdominal wall hematoma, cervical spine stenosis, hypertensive emergency, congestive heart failure, and spinal stenosis (n=1).

dIncluded the following: increased amylase (n=2), increased creatinine (n=1), increased γ‑glutamyltransferase (n=1), serum potassium (hyperkalemia; n=1), increased lipase (n=1), and increased fasting LDL (n=1).

Patient‑reported outcomes at Week 482,3

All participants were “satisfied” or “very satisfied” with BIC/FTC/TAF treatment, with a median (range) HIVTSQ score of 58 (52–60) at baseline (n=10) and 59 (51–60) at Week 48 (n=9). SF-36 scores showed minimal change, with a median (range) change from baseline to Week 48 of 0.5 (-12.9 to 9.5) in the mental component score and -4.9 (-12.2 to 4.9) in the physical component score.

Study of BIC in Participants With Severe Renal Impairment

Study design and demographics

A phase 1, open-label, single-dose, parallel-design study assessed the PK profile, safety, and tolerability of BIC in participants with severe renal impairment (CrClCG, 15–‍29 mL/min). Participants with chronic stable renal impairment not on dialysis (n=10) and healthy volunteers with CrClCG ≥90 mL/min (n=8) were eligible to participate in this study. At screening, all were required to have BMI values of 18 to 40 kg/m2. Participants with severe renal impairment were matched to healthy volunteers with normal renal function based on gender, age, and BMI. Participants and healthy volunteers received a moderate‑fat breakfast followed by a single dose of BIC 75 mg (not commercially available). PK assessments were conducted during the 144‑hour period after dose administration. Safety was assessed throughout the study and during the follow-up period.4,6

The mean (range) age was 62 (22–75) years in the severe renal impairment group and 56 (22–67) years in the normal renal function group. The mean (range) CrClCG was 24 (22–‍26) mL/min in the severe renal impairment group and 107 (90–131) mL/min in the normal renal function group.4

PK results4

The BIC AUC∞ was approximately 27% lower in participants with severe renal impairment than in healthy volunteers with normal renal function (Table 3). No correlation was observed between the AUC∞ or Cmax and eGFRCG.

Table 3. Summary of BIC PK Parameters4

Abbreviations: Fu=unbound fraction; GLSM=geometric least squares mean; Q=quartile; t1/2=terminal half-life.

Safety4

Overall, BIC was well tolerated, and all AEs were Grade 1 in severity. There were 2 AEs, 1 drug-related AE, and no SAEs in each study group. There were 10 laboratory abnormalities in the severe renal impairment group (Grade 1/2/3: 2/4/4) and 4 in the normal renal function group (Grade 1/2/3: 2/2/0).

Case Series

There are limitations in the interpretation of case reports. Case reports cannot be generalized. Unlike controlled clinical trial, causality cannot be inferred based on uncontrolled observational data. In addition, incidence or prevalence cannot be estimated due to the lack of a representative population sample. Other limitations of case reports include the retrospective design and publication bias.7

BIC/FTC/TAF in patients on HD5

A retrospective, single-center case series identified 6 patients on HD who switched to BIC/FTC/TAF-containing regimens between January 2018 and October 2022 (Table 4).

After switching to BIC/FTC/TAF, all patients achieved or maintained virologic suppression, and no patients reported AEs. Patient 1 reported an increased quality of life post switch.

Table 4. Case Series: Summary of Patients on HD Who Switched to BIC/FTC/TAF‑Containing Regimens5

Abbreviations: 1 x/d=one time per day; 2 ×/d=two times per day; 3 ×/d=three times per day; 3TC=lamivudine; AA=African American; ABC=abacavir; ATV=atazanavir; COBI=cobicistat; DDI=drug-drug interaction; DOR=doravirine; DTG=dolutegravir; EVG=elvitegravir; F=female; GI=gastrointestinal; INSTI-R=integrase strand transfer inhibitor resistance; M=male; NNRTI‑R=non-nucleos(t)ide reverse transcriptase inhibitor resistance; NRTI‑R=nucleos(t)ide reverse transcriptase inhibitor resistance; RPV=rilpivirine; RTV=ritonavir; TDF=tenofovir disoproxil fumarate; ZDV=zidovudine.

aPatient 2 was admitted for a GI bleed and required initiation of proton pump inhibitor treatment, which is contraindicated with concomitant RPV.

bPatient 3 was receiving amlodipine and metoprolol tartrate, each of which had the potential to interact with COBI. The patient was also receiving calcium acetate supplementation, which interacts with EVG. There was also a potential for resistance to EVG.

cPatient 4 had a history of NRTI-R (M41L and M184V mutations), NNRTI-R (K103R, V179D, and G190A mutations). There was also an increased cardiovascular risk with ABC.

dPatient 5 had variable adherence to her ARV regimen, and self-discontinued ABC and TDF 2 months prior to the switch. She also had a history of NRTI-R (M184V), NNRTI-R (K103N), and INSTI-R (Q148 and G190S), and severe GI symptoms with protease inhibitors.

ePatient 6 had low-level viremia and occasionally had an undetectable viral load, no resistance, and no concerns for DDIs (calcium supplement dosing was separated from DTG). The patient was required to have an undetectable viral load prior to being considered for a kidney transplant.

fPatient 6 had two consecutive undetectable viral load measurements about 2.5 years after the regimen switch.

References

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

2. Eron JJ, Ramgopal M, Osiyemi O, et al. Bictegravir/emtricitabine/tenofovir alafenamide in adults with HIV-1 and end-stage kidney disease on chronic haemodialysis. HIV Med. 2025;26(2):302-307.

3. Eron JJ, Ramgopal M, Osiyemi O, et al. Bictegravir/emtricitabine/tenofovir alafenamide in adults with HIV-1 and end-stage kidney disease on chronic haemodialysis [Supplement]. HIV Med. 2025;26(2):1-7.

4. Zhang H, Shao Y, Garner W, et al. The Effect of Hepatic or Renal Impairment on Bictegravir Pharmacokinetics [Poster 27]. Paper presented at: 18th International Workshop on Clinical Pharmacology of Antiviral Therapy; 14-16 June, 2017; Chicago, IL.

5. Sidman EF, Ondrush NM. Utilization of bictegravir/emtricitabine/tenofovir alafenamide in patients with end-stage renal disease on hemodialysis. Am J Health Syst Pharm. 2023;80(9):e92-e97.

6. ClinicalTrials.gov. Pharmacokinetics of Bictegravir in Adults With Normal and Impaired Renal Function. ClinicalTrials.gov Identifier: NCT02400307. Available at: https://clinicaltrials.gov/ct2/show/NCT02400307?term=NCT02400307.

7. Nissen T, Wynn R. The Clinical Case Report: A Review of Its Merits and Limitations. BMC Res Notes. 2014;7:264.

Abbreviations

AE=adverse event
ARV=antiretroviral
AUC∞=area under the curve to time infinity
BIC=bictegravir
c/mL=copies/mL
Cmax=peak concentration
CG=Cockcroft–Gault equation
Ctrough=trough concentration
CV=coefficient of variation
E/C/F/TAF=elvitegravir/
cobicistat/emtricitabine/
tenofovir alafenamide
ESRD=end-stage renal disease
FTC=emtricitabine
HD=hemodialysis
HIVTSQ=HIV Treatment Satisfaction Questionnaire
M=E=missing=excluded
OLE=open‑label extension
paEC95=protein-adjusted 95% effective concentration
PK=pharmacokinetic(s)
PWH=people with HIV-1
SAE=serious adverse event
SF-36=36-Item Short Form Health Survey
TAF=tenofovir alafenamide

 

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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