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NCT03547908: Alliance

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

Completed Phase 3 Results posted Last updated 19 March 2025
What this trial tests

Phase 3 trial testing B/F/TAF in HIV-1/HBV Co-Infection in 244 participants. Completed in 7 March 2024.

Timeline
30 May 2018
Primary endpoint
25 February 2022
7 March 2024

Quick facts

Lead sponsorGilead Sciences
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment244
Start date30 May 2018
Primary completion25 February 2022
Estimated completion7 March 2024
Sites69 locations across France, Hong Kong, Japan, Dominican Republic, Greece, Malaysia, Taiwan, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with HIV-1/HBV Co-Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · Week 48

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.

GroupValue95% CI
Blinded Phase: B/F/TAF95.0
Blinded Phase: DTG + F/TDF91.0
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) Primary · Week 48

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.

GroupValue95% CI
Blinded Phase: B/F/TAF63.0
Blinded Phase: DTG + F/TDF43.4
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm Secondary · Week 96

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.

GroupValue95% CI
Blinded Phase: B/F/TAF87.4
Blinded Phase: DTG + F/TDF87.7
Change From Baseline in CD4 Cell Count at Week 48 Secondary · Baseline, Week 48
GroupValue95% CI
Blinded Phase: B/F/TAF200± 139.3
Blinded Phase: DTG + F/TDF175± 124.7
Change From Baseline in CD4 Cell Count at Week 96 Secondary · Baseline, Week 96
GroupValue95% CI
Blinded Phase: B/F/TAF261± 161.6
Blinded Phase: DTG + F/TDF229± 174.0
Change From Baseline in Percentage of CD4 Cells at Week 48 Secondary · Baseline, Week 48
GroupValue95% CI
Blinded Phase: B/F/TAF8.43± 4.1
Blinded Phase: DTG + F/TDF7.75± 4.3
Change From Baseline in Percentage of CD4 Cells at Week 96 Secondary · Baseline, Week 96
GroupValue95% CI
Blinded Phase: B/F/TAF10.69± 5.047
Blinded Phase: DTG + F/TDF10.42± 5.096
Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96 Secondary · 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.

GroupValue95% CI
Blinded Phase: B/F/TAF74.8
Blinded Phase: DTG + F/TDF70.5
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 by American Association for the Study of Liver Diseases (AASLD) Criteria Secondary · Week 48

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.

GroupValue95% CI
Blinded Phase: B/F/TAF73.3
Blinded Phase: DTG + F/TDF55.3
Percentage of Participants With ALT Normalization at Week 96 Secondary · 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.

GroupValue95% CI
Blinded Phase: B/F/TAF71.7
Blinded Phase: DTG + F/TDF57.4
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 Secondary · 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.

GroupValue95% CI
Blinded Phase: B/F/TAF12.6
Blinded Phase: DTG + F/TDF5.8
Percentage of Participants With HBsAg Loss at Week 96 Secondary · 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.

GroupValue95% CI
Blinded Phase: B/F/TAF22.7
Blinded Phase: DTG + F/TDF14.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events: Up to the last dose date plus 30 days (maximum exposure: 5.1 years); All-Cause Mortality: Up to 5.3 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Blinded Phase: B/F/TAF
Serious: 17/121 (14%)
Deaths: 2/122
Blinded Phase: DTG + F/TDF
Serious: 16/122 (13%)
Deaths: 1/122
Open-Label Extension Phase: B/F/TAF From B/F/TAF
Serious: 4/95 (4%)
Deaths: 1/95
Open-Label Extension Phase: B/F/TAF From DTG+F/TDF
Serious: 2/89 (2%)
Deaths: 0/89

Serious adverse events (39 terms)

ReactionSystemBlinded Phase: B/F/TAFBlinded Phase: DTG + F/TDFOpen-Label Extension Phase…Open-Label Extension Phase…
Covid-19Infections and infestations
HaemorrhoidsGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Myocardial ischaemiaCardiac disorders
Rhegmatogenous retinal detachmentEye disorders
Anal fistulaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
EnteritisGastrointestinal disorders
Haemorrhoids thrombosedGastrointestinal disorders
Irritable bowel syndromeGastrointestinal disorders
Lumbar herniaGastrointestinal disorders
Death, not otherwise specifiedGeneral disorders
Influenza like illnessGeneral disorders
Anal abscessInfections and infestations
AppendicitisInfections and infestations
Bacterial sepsisInfections and infestations
Cytomegalovirus chorioretinitisInfections and infestations
Dengue haemorrhagic feverInfections and infestations
GastroenteritisInfections and infestations
Groin abscessInfections and infestations
Hepatic amoebiasisInfections and infestations
Meningitis cryptococcalInfections and infestations
MycotoxicosisInfections and infestations
OrchitisInfections and infestations
Pneumocystis jirovecii pneumoniaInfections and infestations
Other adverse events (25 terms — click to expand)

ReactionSystemBlinded Phase: B/F/TAFBlinded Phase: DTG + F/TDFOpen-Label Extension Phase…Open-Label Extension Phase…
Covid-19Infections and infestations
Upper respiratory tract infectionInfections and infestations
NasopharyngitisInfections and infestations
PyrexiaGeneral disorders
Alanine aminotransferase increasedInvestigations
DiarrhoeaGastrointestinal disorders
Weight increasedInvestigations
HeadacheNervous system disorders
SyphilisInfections and infestations
Aspartate aminotransferase increasedInvestigations
DizzinessNervous system disorders
RashSkin and subcutaneous tissue disorders
Acute hepatitis CInfections and infestations
Back painMusculoskeletal and connective tissue disorders
GastritisGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
HaemorrhoidsGastrointestinal disorders
Influenza like illnessGeneral disorders
FolliculitisInfections and infestations
Latent syphilisInfections and infestations
Secondary syphilisInfections and infestations
Vaccination complicationInjury, poisoning and procedural complications
HyperuricaemiaMetabolism and nutrition disorders
Abnormal weight gainMetabolism and nutrition disorders

Most-reported serious reactions: Covid-19, Haemorrhoids, Anaemia, Myocardial ischaemia, Rhegmatogenous retinal detachment, Anal fistula, Diarrhoea, Enteritis.

Data from ClinicalTrials.gov NCT03547908 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. HBV/HIV Coinfection: Impact on the Development and Clinical Treatment of Liver Diseases.
    Cheng Z, Lin P, Cheng N. · · 2021 · cited 44× · PMID 34676223 · DOI 10.3389/fmed.2021.713981
  2. 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.
    Avihingsanon A, Lu H, Leong CL, Hung CC, et al · · 2023 · cited 34× · PMID 37494942 · DOI 10.1016/s2352-3018(23)00151-0
  3. Selected nucleos(t)ide-based prescribed drugs and their multi-target activity.
    Pastuch-Gawołek G, Gillner D, Król E, Walczak K, et al · · 2019 · cited 23× · PMID 31634460 · DOI 10.1016/j.ejphar.2019.172747
  4. Meta-Analysis of Efficacy and Safety of Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Among People Living with HIV.
    Chen IW, Sun HY, Hung CC. · · 2021 · cited 13× · PMID 33977505 · DOI 10.1007/s40121-021-00449-z
  5. Special Issue: Abstract Supplement HIV Glasgow 10-13 November 2024, Glasgow, UK/Virtual.
    · 2024 · cited 8× · PMID 39513741 · DOI 10.1002/jia2.26370
  6. Efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-based three-drug regimens in people with HIV with varying adherence to antiretroviral therapy.
    Andreatta K, Sax PE, Wohl D, D'Antoni ML, et al · · 2025 · cited 6× · PMID 39556192 · DOI 10.1093/jac/dkae407
  7. Renal Outcomes in People With HIV-1 and Renal Impairment Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide: Integrated Analysis From 9 Phase 3/3b Clinical Trials.
    Post FA, Wohl D, Liegeon G, Brar I, et al · · 2026 · PMID 42182842 · DOI 10.1093/ofid/ofag265
  8. 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.
    D'Antoni ML, Boopathy AV, Andreatta K, Chang S, et al · · 2025 · PMID 40857111 · DOI 10.1097/qai.0000000000003749

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