Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment Naive, HIV-1 and Hepatitis B Co-Infected Adults

NCT03547908 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-380-44582018-000926-79
• Study Type: interventional
• Target: 244
• Locations: 14 countries
• Sites: 69

Brief Summary

The primary objective of this study is to evaluate the efficacy of fixed-dose combination (FDC) of bictegravir/emtricitabine/ tenofovir alafenamide (B/F/TAF) versus dolutegravir (DTG) + emtricitabine/tenofovir disoproxil fumarate (F/TDF) in treatment-naïve and HIV-1 and hepatitis B virus (HBV) adults.

Conditions

HIV-1/HBV Co-Infection

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm (Co-primary Endpoint)

  The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Percentages were rounded-off.

  Week 48

• Percentage of Participants With Plasma Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48 as Defined by Missing = Failure Approach (Co-primary Endpoint)

  This outcome measure was analyzed using a Missing = Failure approach. In this approach, all missing data were treated as HBV DNA ≥ 29 IU/mL. Percentages were rounded-off.

  Week 48

Secondary Outcomes (10)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm

  Week 96

• Change From Baseline in CD4 Cell Count at Week 48

  Baseline, Week 48

• Change From Baseline in CD4 Cell Count at Week 96

  Baseline, Week 96

• Change From Baseline in Percentage of CD4 Cells at Week 48

  Baseline, Week 48

• Change From Baseline in Percentage of CD4 Cells at Week 96

  Baseline, Week 96

Study Arms (4)

Blinded Phase: B/F/TAF

EXPERIMENTAL

Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) tablet in addition to placebo to match (PTM) dolutegravir (DTG) tablet and PTM FDC emtricitabine/ tenofovir desoproxil fumarate (F/TDF) tablet for 96 weeks.

Drug: B/F/TAF; Drug: Placebo to match DTG; Drug: Placebo to match F/TDF

Blinded Phase: DTG+F/TDF

ACTIVE COMPARATOR

Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive DTG and FDC F/TDF in addition to PTM B/F/TAF for 96 weeks.

Drug: DTG; Drug: F/TDF; Drug: Placebo to match B/F/TAF

Open-label Extension Phase: B/F/TAF from B/F/TAF

EXPERIMENTAL

After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 48 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.

Drug: B/F/TAF

Open-label Extension Phase: B/F/TAF from DTG+F/TDF

EXPERIMENTAL

After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 48 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.

Drug: B/F/TAF

Interventions

B/F/TAF DRUG

50/200/25 mg B/F/TAF FDC tablet administered orally once daily, without regard to food

Also known as: Biktarvy®

Blinded Phase: B/F/TAF; Open-label Extension Phase: B/F/TAF from B/F/TAF; Open-label Extension Phase: B/F/TAF from DTG+F/TDF

Placebo to match DTG DRUG

Tablet administered orally once daily, without regard to food

Blinded Phase: B/F/TAF

Placebo to match F/TDF DRUG

Tablet administered orally once daily, without regard to food

Blinded Phase: B/F/TAF

DTG DRUG

50 mg tablet administered orally once daily, without regard to food

Blinded Phase: DTG+F/TDF

F/TDF DRUG

200/300 mg tablet administered orally once daily, without regard to food

Also known as: Truvada®

Blinded Phase: DTG+F/TDF

Placebo to match B/F/TAF DRUG

Tablet administered orally once daily, without regard to food

Blinded Phase: DTG+F/TDF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Human immunodeficiency virus type 1 (HIV-1) co-infection:
• Must be HIV antiretroviral treatment naive with plasma HIV-1 ribonucleic acid (RNA) ≥ 500 copies/mL at screening
• ≤ 10 days of prior therapy with any antiretroviral agent, including lamivudine and entecavir, following a diagnosis of HIV-1 infection (except the use for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to one month prior to screening)

You may not qualify if:

• HBV co-infection:
• Must be hepatitis B virus (HBV) treatment naive (defined as \< 12 weeks of oral antiviral treatment)
• Screening HBV deoxyribonucleic acid (DNA) ≥ 2000 IU/mL
• Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) ≤ 10 x upper limit of normal (ULN)
• Total bilirubin ≤ 2.5 x ULN
• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
• Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or with Child-Pugh-Turcotte (CPT) C impairment
• Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
• Active, serious infections (other than HIV-1 and HBV infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
• Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (69)

Midway Immunology & Research

Ft. Pierce, Florida, 34982, United States

Location

Triple O Research Institute, P.A.

West Palm Beach, Florida, 33401, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA)

Houston, Texas, 77098, United States

Location

Beijing Ditan Hospital Capital Medical University

Beijing, 100015, China

Location

Beijing YouAn Hospital, Capital Medical University

Beijing, 100069, China

Location

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, 100730, China

Location

The First Hospital of Changsha

Changsha, 410005, China

Location

Chengdu Public Health Clinical Center

Chengdu, 610066, China

Location

Guangzhou Eighth people's Hospital

Guangzhou, 510060, China

Location

1st Affiliated Hospital of Zhejiang University

Hangzhou, China

Location

The Second Hospital of Nanjing

Nanjing, China

Location

Shanghai Public Health Clinical Center

Shanghai, 201058, China

Location

Third People's Hospital Of Shenzhen

Shenzhen, 518040, China

Location

Instituto Dominicano de Estudios Virologicos (IDEV)

Santo Domingo, 10103, Dominican Republic

Location

Hôpital de la Croix Rousse

Lyon, 69004, France

Location

Evaggelismos General Hospital of Athens

Athens, 10676, Greece

Location

Korgialenio-Benakio Greek Red Cross General Hospital

Athens, 11526, Greece

Location

Laiko General Hospital

Athens, 11527, Greece

Location

AHEPA University Hospital of Thessaloniki

Thessaloniki, 546 36, Greece

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Elizabeth Hospital (QEH)

Hong Kong, Hong Kong

Location

Princess Margaret Hospital

Kowloon, Hong Kong

Location

National Hospital Organization Nagoya Medical Center

Aichi, 460-0001, Japan

Location

University of the Ryukyus Hospital

Okinawa, 903-0215, Japan

Location

Osaka City General Hospital

Osaka, 534-0021, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, 540-0006, Japan

Location

The Jikei University Hospital

Tokyo, 105-8471, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Center Hospital of the National Center for Global Health and Medicine

Tokyo, 162-8655, Japan

Location

Yokohama City University Hospital

Yokohama, 236-0004, Japan

Location

Hospital Raja Permaisuri Bainun

Ipoh, 31350, Malaysia

Location

Hospital Raja Perempuan Zainab II

Kota Bharu, 15580, Malaysia

Location

Queen Elizabeth Hospital

Kota Kinabalu, 88200, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 50603, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, 53000, Malaysia

Location

Hospital Sultanah Nur Zahirah

Kuala Terengganu, 20400, Malaysia

Location

Sarawak General Hospital

Kuching, 93586, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, 10450, Malaysia

Location

Sungai Buloh Hospital

Sungai Buloh, 47000, Malaysia

Location

Hope Clinical Research

San Juan, 00909, Puerto Rico

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Santa Lucia

Cartagena, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital de Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

CHUVI - Hospital Universitario Alvaro Cunqueiro

Vigo, 36312, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, 81362, Taiwan

Location

Far Eastern Memorial Hospital

New Taipei City, 22060, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Taipei City Hospital Linsen, Chinese Medicine and Kunming Branch

Taipei, 10844, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Ministry of Health and Welfare Taoyuan General Hospital

Taoyuan, 33004, Taiwan

Location

Thai Red Cross AIDS Research Centre (HIV-NAT)

Bangkok, 10330, Thailand

Location

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Faculty of Medicine, Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Chiang Rai Reginal Hospital

Chiang Rai, 57000, Thailand

Location

Srinagarind Hospital

Khon Kaen, 40002, Thailand

Location

Bamrasnaradura Infectious Diseases Institute

Nonthaburi, 11000, Thailand

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

Marmara University Pendik Training and Research Hospital

Istanbul, 81190, Turkey (Türkiye)

Location

Related Publications (9)

• Avihingsanon, A. 2022. Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir Disoproxil Fumarate (DTG+F/TDF) as initial treatment in HIV/HBV-coinfected adults (ALLIANCE). AIDS, 29 July 29-2 August 2022, Montréal, Québec, Canada.

  BACKGROUND

• Avihingsanon A, Lu H, Leong CL, Hung CC, Koenig E, Kiertiburanakul S, Lee MP, Supparatpinyo K, Zhang F, Rahman S, D'Antoni ML, Wang H, Hindman JT, Martin H, Baeten JM, Li T; ALLIANCE Study Team. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial. Lancet HIV. 2023 Oct;10(10):e640-e652. doi: 10.1016/S2352-3018(23)00151-0. Epub 2023 Jul 23.

  PMID: 37494942 BACKGROUND

• D'Antoni ML, Andreatta K, Chang S, Cox S, Hindman JT, Avihingsanon A, Martin H, VanderVeen LA, Callebaut C. Brief Report: HIV-1 Resistance Analysis of Participants With HIV-1 and Hepatitis B Initiating Therapy With Bictegravir/Emtricitabine/Tenofovir Alafenamide or Dolutegravir Plus Emtricitabine/Tenofovir Disoproxil Fumarate: A Subanalysis of ALLIANCE Data. J Acquir Immune Defic Syndr. 2024 Aug 1;96(4):380-384. doi: 10.1097/QAI.0000000000003434. Epub 2024 Jun 21.

  PMID: 40788226 BACKGROUND

• Avihingsanon A, Lu H, Leong CL, Hung C-C, Kiertiburanakul S, Lee M-P, Supparatpinyo K, Zhang F, Hindman JT, Wang H, Liu H and Li T. Factors Associated with HBV Response to B/F/TAF vs. DTG + F/TDF at W96 in People with HIV-1 and HBV. CROI, March 3-6, 2024.

  BACKGROUND

• Avihingsanon A, Lu H, Leong C, Hung C, Koenig E, Kiertiburanakul S, et al. Week-96 results of ALLIANCE, a Phase 3, randomized, double-blind study comparing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) in treatment-naive people with both HIV-1 and hepatitis B. 12th International AIDS Society Conference on HIV Science 2023, 23-26 July.

  BACKGROUND

• D'Antoni M, Andreatta K, Cox S, Chang S, Hindman J, Martin H, et al. HIV-1 resistance analysis of treatment-naive participants with HIV-1 and hepatitis B coinfection receiving bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir + emtricitabine/tenofovir disoproxil fumarate. European Meeting on HIV and Hepatitis 2023, 7-9 June, Rome, Italy.

  BACKGROUND

• Avihingsanon A, Leong C, Hung C, Koenig E, Lee M, Supparatpinyo K, et al. Predictors of hepatitis B treatment response in people with HIV-1/HBV coinfection. Conference on Retroviruses and Opportunistic Infections (CROI) 2023, 19-22 February; Seattle, Washington.

  BACKGROUND

• Avihingsanon A, Lu H, Leong C, Hung C, Koenig E, Kiertiburanakul S, et al. Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) as initial treatment in HIV/HBV coinfected adults (ALLIANCE). AIDS (Conference) 2022, 29 July 2 August; Montréal, Québec, Canada.

  BACKGROUND

• D'Antoni ML, Boopathy AV, Andreatta K, Chang S, Hindman JT, Avihingsanon A, VanderVeen LA, Callebaut C. Brief Report: HIV-1 Resistance Analysis of Participants With HIV-1 and Hepatitis B Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide or Dolutegravir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Through the Open-Label Extension of the ALLIANCE Study. J Acquir Immune Defic Syndr. 2025 Dec 1;100(4):342-346. doi: 10.1097/QAI.0000000000003749.

  PMID: 40857111 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 6, 2018
• Study Start: May 30, 2018
• Primary Completion: February 25, 2022
• Study Completion: March 7, 2024
• Last Updated: March 19, 2025
• Results First Posted: March 15, 2023

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

FR (1); DO (1); PR (1); KR (2); US (4); ES (8); MY (9); GR (4); TW (9); TH (7); TU (2); HK (3); CN (10); JP (8)