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

NCT ID: NCT03547908

Last Updated: 2025-03-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

244 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-30

Study Completion Date

2024-03-07

Brief Summary

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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.

Detailed Description

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Conditions

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HIV-1/HBV Co-Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Blinded Phase: B/F/TAF

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.

Group Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

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

Placebo to match DTG

Intervention Type DRUG

Tablet administered orally once daily, without regard to food

Placebo to match F/TDF

Intervention Type DRUG

Tablet administered orally once daily, without regard to food

Blinded Phase: DTG+F/TDF

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.

Group Type ACTIVE_COMPARATOR

DTG

Intervention Type DRUG

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

F/TDF

Intervention Type DRUG

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

Placebo to match B/F/TAF

Intervention Type DRUG

Tablet administered orally once daily, without regard to food

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

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.

Group Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

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

Interventions

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B/F/TAF

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

Intervention Type DRUG

Placebo to match DTG

Tablet administered orally once daily, without regard to food

Intervention Type DRUG

Placebo to match F/TDF

Tablet administered orally once daily, without regard to food

Intervention Type DRUG

DTG

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

Intervention Type DRUG

F/TDF

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

Intervention Type DRUG

Placebo to match B/F/TAF

Tablet administered orally once daily, without regard to food

Intervention Type DRUG

Other Intervention Names

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Biktarvy® Truvada®

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Midway Immunology & Research

Ft. Pierce, Florida, United States

Site Status

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Site Status

Be Well Medical Center

Berkley, Michigan, United States

Site Status

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

Houston, Texas, United States

Site Status

Beijing Ditan Hospital Capital Medical University

Beijing, , China

Site Status

Beijing YouAn Hospital, Capital Medical University

Beijing, , China

Site Status

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Site Status

The First Hospital of Changsha

Changsha, , China

Site Status

Chengdu Public Health Clinical Center

Chengdu, , China

Site Status

Guangzhou Eighth people's Hospital

Guangzhou, , China

Site Status

1st Affiliated Hospital of Zhejiang University

Hangzhou, , China

Site Status

The Second Hospital of Nanjing

Nanjing, , China

Site Status

Shanghai Public Health Clinical Center

Shanghai, , China

Site Status

Third People's Hospital Of Shenzhen

Shenzhen, , China

Site Status

Instituto Dominicano de Estudios Virologicos (IDEV)

Santo Domingo, , Dominican Republic

Site Status

Hôpital de la Croix Rousse

Lyon, , France

Site Status

Evaggelismos General Hospital of Athens

Athens, , Greece

Site Status

Korgialenio-Benakio Greek Red Cross General Hospital

Athens, , Greece

Site Status

Laiko General Hospital

Athens, , Greece

Site Status

AHEPA University Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status

Queen Elizabeth Hospital (QEH)

Hong Kong, , Hong Kong

Site Status

Princess Margaret Hospital

Kowloon, , Hong Kong

Site Status

National Hospital Organization Nagoya Medical Center

Aichi, , Japan

Site Status

University of the Ryukyus Hospital

Okinawa, , Japan

Site Status

Osaka City General Hospital

Osaka, , Japan

Site Status

National Hospital Organization Osaka National Hospital

Osaka, , Japan

Site Status

The Jikei University Hospital

Tokyo, , Japan

Site Status

Juntendo University Hospital

Tokyo, , Japan

Site Status

Center Hospital of the National Center for Global Health and Medicine

Tokyo, , Japan

Site Status

Yokohama City University Hospital

Yokohama, , Japan

Site Status

Hospital Raja Permaisuri Bainun

Ipoh, , Malaysia

Site Status

Hospital Raja Perempuan Zainab II

Kota Bharu, , Malaysia

Site Status

Queen Elizabeth Hospital

Kota Kinabalu, , Malaysia

Site Status

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Site Status

Hospital Sultanah Nur Zahirah

Kuala Terengganu, , Malaysia

Site Status

Sarawak General Hospital

Kuching, , Malaysia

Site Status

Hospital Pulau Pinang

Pulau Pinang, , Malaysia

Site Status

Sungai Buloh Hospital

Sungai Buloh, , Malaysia

Site Status

Hope Clinical Research

San Juan, , Puerto Rico

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital General Universitario Santa Lucia

Cartagena, , Spain

Site Status

Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital de Canarias

Santa Cruz de Tenerife, , Spain

Site Status

Hospital General Universitario de Valencia

Valencia, , Spain

Site Status

CHUVI - Hospital Universitario Alvaro Cunqueiro

Vigo, , Spain

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Site Status

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei City Hospital Linsen, Chinese Medicine and Kunming Branch

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Ministry of Health and Welfare Taoyuan General Hospital

Taoyuan, , Taiwan

Site Status

Thai Red Cross AIDS Research Centre (HIV-NAT)

Bangkok, , Thailand

Site Status

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, , Thailand

Site Status

Siriraj Hospital

Bangkok, , Thailand

Site Status

Faculty of Medicine, Chiang Mai University

Chiang Mai, , Thailand

Site Status

Chiang Rai Reginal Hospital

Chiang Rai, , Thailand

Site Status

Srinagarind Hospital

Khon Kaen, , Thailand

Site Status

Bamrasnaradura Infectious Diseases Institute

Nonthaburi, , Thailand

Site Status

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Site Status

Marmara University Pendik Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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United States China Dominican Republic France Greece Hong Kong Japan Malaysia Puerto Rico South Korea Spain Taiwan Thailand Turkey (Türkiye)

References

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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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 37494942 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 40788226 (View on PubMed)

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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type DERIVED
PMID: 40857111 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan - Interim Analysis

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan - Final Analysis

View Document

Related Links

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Other Identifiers

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2018-000926-79

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-380-4458

Identifier Type: -

Identifier Source: org_study_id

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