HIV-1/HBV Co-InfectionPhase 3AllianceNCT03547908

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

A Phase 3 study testing B/F/TAF, DTG and F/TDF in people with HIV-1/HBV Co-Infection, run by Gilead Sciences at 69 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV-1/HBV Co-Infection
What is being tested?: B/F/TAF, DTG and F/TDF
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 244 participants
Where: 69 sitesin 14 countries
Study dates: 30 May 2018to 7 Mar 2024
Phase: Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)
Screening genotype report must show sensitivity to emtricitabine (FTC) and tenofovir (TFV). This report will be provided by Gilead Sciences. Alternatively, if genotype results from a local laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype will be acceptable to fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been confirmed
HBV co-infection:
Must be hepatitis B virus (HBV) treatment naive (defined as < 12 weeks of oral antiviral treatment)

Show all 9Show fewer

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

Who cannot join

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
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

69 sites in 14 countries.

Country

City, postcode or hospital

69 sites in 14 countries

China10 sites

Beijing Ditan Hospital Capital Medical University
Beijing, 100015
Beijing YouAn Hospital, Capital Medical University
Beijing, 100069
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Beijing, 100730
The First Hospital of Changsha
Changsha, 410005
Chengdu Public Health Clinical Center
Chengdu, 610066
Guangzhou Eighth people's Hospital
Guangzhou, 510060
1st Affiliated Hospital of Zhejiang University
Hangzhou
The Second Hospital of Nanjing
Nanjing
Shanghai Public Health Clinical Center
Shanghai, 201058
Third People's Hospital Of Shenzhen
Shenzhen, 518040

Other trials in China

Malaysia9 sites

Hospital Raja Permaisuri Bainun
Ipoh, 31350
Hospital Raja Perempuan Zainab II
Kota Bharu, 15580
Queen Elizabeth Hospital
Kota Kinabalu, 88200
University Malaya Medical Centre
Kuala Lumpur, 50603
Hospital Kuala Lumpur
Kuala Lumpur, 53000
Hospital Sultanah Nur Zahirah
Kuala Terengganu, 20400
Sarawak General Hospital
Kuching, 93586
Hospital Pulau Pinang
Pulau Pinang, 10450
Sungai Buloh Hospital
Sungai Buloh, 47000

Other trials in Malaysia

Taiwan9 sites

Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 80756
Kaohsiung Veterans General Hospital
Kaohsiung City, 81362
Far Eastern Memorial Hospital
New Taipei City, 22060
Taichung Veterans General Hospital
Taichung, 40705
National Cheng Kung University Hospital
Tainan, 70403
National Taiwan University Hospital
Taipei, 10048
Taipei City Hospital Linsen, Chinese Medicine and Kunming Branch
Taipei, 10844
Taipei Veterans General Hospital
Taipei, 11217
Ministry of Health and Welfare Taoyuan General Hospital
Taoyuan City, 33004

Other trials in Taiwan

Japan8 sites

National Hospital Organization Nagoya Medical Center
Aichi, 460-0001
University of the Ryukyus Hospital
Okinawa, 903-0215
Osaka City General Hospital
Osaka, 534-0021
National Hospital Organization Osaka National Hospital
Osaka, 540-0006
The Jikei University Hospital
Tokyo, 105-8471
Juntendo University Hospital
Tokyo, 113-8431
Center Hospital of the National Center for Global Health and Medicine
Tokyo, 162-8655
Yokohama City University Hospital
Yokohama, 236-0004

Other trials in Japan

Spain8 sites

Hospital Clinic de Barcelona
Barcelona, 08036
Hospital General Universitario Santa Lucia
Cartagena
Fundacion Jimenez Diaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital de Canarias
Santa Cruz de Tenerife, 38320
Hospital General Universitario de Valencia
Valencia, 46014
CHUVI - Hospital Universitario Alvaro Cunqueiro
Vigo, 36312

Other trials in Spain

Thailand7 sites

Thai Red Cross AIDS Research Centre (HIV-NAT)
Bangkok, 10330
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Bangkok, 10400
Siriraj Hospital
Bangkok, 10700
Faculty of Medicine, Chiang Mai University
Chiang Mai, 50200
Chiang Rai Reginal Hospital
Chiang Rai, 57000
Srinagarind Hospital
Khon Kaen, 40002
Bamrasnaradura Infectious Diseases Institute
Nonthaburi, 11000

Other trials in Thailand

United States4 sites

Be Well Medical Center
Berkley, Michigan, 48072
Midway Immunology & Research
Ft. Pierce, Florida, 34982
The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA)
Houston, Texas, 77098
Triple O Research Institute, P.A.
West Palm Beach, Florida, 33401

Other trials in United States

Greece4 sites

Evaggelismos General Hospital of Athens
Athens, 10676
Korgialenio-Benakio Greek Red Cross General Hospital
Athens, 11526
Laiko General Hospital
Athens, 11527
AHEPA University Hospital of Thessaloniki
Thessaloniki, 546 36

Other trials in Greece

Hong Kong3 sites

Prince of Wales Hospital
Hong Kong
Queen Elizabeth Hospital (QEH)
Hong Kong
Princess Margaret Hospital
Kowloon

Other trials in Hong Kong

South Korea2 sites

Pusan National University Hospital
Busan, 49241
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591

Other trials in South Korea

Turkey (Türkiye)2 sites

Istanbul University Cerrahpasa Medical Faculty
Istanbul, 34098
Marmara University Pendik Training and Research Hospital
Istanbul, 81190

Other trials in Turkey (Türkiye)

Dominican Republic1 site

Instituto Dominicano de Estudios Virologicos (IDEV)
Santo Domingo, 10103

Other trials in Dominican Republic

France1 site

Hôpital de la Croix Rousse
Lyon, 69004

Other trials in France

Puerto Rico1 site

Hope Clinical Research
San Juan, 00909

Other trials in Puerto Rico

About this study

Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Fixed Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment Naïve, HIV-1 and Hepatitis B Co-Infected Adults

Conditions: HIV-1/HBV Co-Infection
Being tested: B/F/TAF, Placebo to match DTG, Placebo to match F/TDF, DTG, F/TDF

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

B/F/TAFDrug
Also called Biktarvy®
50/200/25 mg B/F/TAF FDC tablet administered orally once daily, without regard to food
Placebo to match DTGDrug
Tablet administered orally once daily, without regard to food
Placebo to match F/TDFDrug
Tablet administered orally once daily, without regard to food
DTGDrug
50 mg tablet administered orally once daily, without regard to food
F/TDFDrug
Also called Truvada®
200/300 mg tablet administered orally once daily, without regard to food
Placebo to match B/F/TAFDrug
Tablet administered orally once daily, without regard to food

Study groups in NCT03547908
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: B/F/TAF

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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
The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which was defined as 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.
Measured: Week 96
Change From Baseline in CD4 Cell Count at Week 48
Measured: Baseline, Week 48
Change From Baseline in CD4 Cell Count at Week 96
Measured: Baseline, Week 96
Change From Baseline in Percentage of CD4 Cells at Week 48
Measured: Baseline, Week 48
Change From Baseline in Percentage of CD4 Cells at Week 96
Measured: Baseline, Week 96
Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96
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.
Measured: Week 96
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 by American Association for the Study of Liver Diseases (AASLD) Criteria
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given post baseline visit. The upper limit of the normal range (ULN) for ALT using the 2018 AASLD normal range was ≤ 25 U/L for females and ≤ 35 U/L for males. The Missing = Failure approach was used for this analysis. Percentages were rounded off.
Measured: Week 48
Percentage of Participants With ALT Normalization at Week 96
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given post baseline visit. The upper limit of the normal range (ULN) for ALT using the 2018 AASLD normal range was ≤ 25 U/L for females and ≤ 35 U/L for males. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Measured: Week 96
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a post baseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative or missing at baseline to positive at a post baseline visit. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Measured: Week 48
Percentage of Participants With HBsAg Loss at Week 96
HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a post baseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative or missing at baseline to positive at a post baseline visit. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Measured: Week 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 May 20187 Mar 2024

First posted6 Jun 2018
Study start30 May 2018
Primary completion25 Feb 2022
Study completion7 Mar 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for HIV-1/HBV Co-InfectionStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 244 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03547908
Sponsor's protocol ID: GS-US-380-4458
Other IDs: 2018-000926-79, 2018
Acronym: Alliance
Status last verified: Feb 2025
First submitted: 24 May 2018
Last updated: 19 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment

Publications

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.
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.
PubMed 37494942
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.
PubMed 40788226
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.
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.
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.
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.
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.
Avihingsanon A, Leong CL, Hung CC, Kiertiburanakul S, Lee MP, D'Antoni ML, Madera S, Wang H, Hindman JT, Li T. B/F/TAF in people with both HIV-1 and hepatitis B: outcomes from the ALLIANCE open-label extension phase. AIDS Res Ther. 2026 Jul 16. doi: 10.1186/s12981-026-00891-4. Online ahead of print.
PubMed 42464361
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.
PubMed 40857111