A Study to Evaluate the Efficacy, Safety, and Tolerability of Using an Oral Once-daily 2 Drug Regimen Compared to an Oral Once-daily 3 Drug Regimen for the Treatment of Human Immunodeficiency Virus (HIV)-1 in Adults Who Have Not Previously Taken Antiretroviral Therapy

NCT05979311 | Active Not Recruiting Phase 3

• 1 other identifier: 219816
• Study Type: interventional
• Target: 473
• Locations: 17 countries
• Sites: 64

Brief Summary

This study will compare safety, efficacy, participant reported outcomes and implementation outcomes of a fixed dose combination (FDC) of a two-drug regimen dolutegravir (DTG) plus lamivudine (3TC) and a three-drug regimen FDC of bictegravir (BIC), emtricitabine (FTC) and tenofovir alafenamide (TAF) in HIV-1 infected adult participants who have not previously received antiretroviral therapy.

Conditions

HIV; HIV Infections

Keywords

Antiretroviral-naïve; Bictegravir; Dolutegravir; Emtricitabine; Human immunodeficiency virus 1 (HIV-1); Lamivudine; Virologic suppression; Tenofovir alafenamide

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with plasma HIV- Ribonucleic acid (RNA) less than (<)50 copies per milliliter (c/mL) as per snapshot algorithm at Week 48

  Week 48

Secondary Outcomes (41)

• Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Weeks 24 and 96

  Weeks 24 and 96

• Percentage of participants with HIV-RNA greater than or equal to (>=)50 c/mL as per snapshot algorithm at Weeks 24, 48, and 96

  Weeks 24, 48 and 96

• Change from Baseline in HIV-1 RNA at Weeks 24, 48 and 96

  Baseline (Day 1) and Weeks 24, 48 and 96

• Change from Baseline in Cluster of differentiation 4 positive (CD4+) cell count at Weeks 24, 48 and 96

  Baseline (Day 1) and Weeks 24, 48 and 96

• Change from Baseline in CD4/Cluster of differentiation 8 (CD8) at Weeks 24, 48 and 96

  Baseline (Day 1) and Weeks 24, 48 and 96

Study Arms (2)

DTG/3TC

EXPERIMENTAL

Participants will receive FDC of DTG/3TC once daily until Week 96.

Drug: Dolutegravir; Drug: Lamivudine

BIC/FTC/TAF

ACTIVE COMPARATOR

Participants will receive BIC/FTC/TAF once daily until Week 96.

Drug: Bictegravir; Drug: Emtricitabine; Drug: Tenofovir alafenamide

Interventions

Dolutegravir DRUG

Dolutegravir will be administered once daily.

DTG/3TC

Lamivudine DRUG

Lamivudine will be administered once daily.

DTG/3TC

Bictegravir DRUG

Bictegravir will be administered once daily.

BIC/FTC/TAF

Emtricitabine DRUG

Emtricitabine will be administered once daily.

BIC/FTC/TAF

Tenofovir alafenamide DRUG

Tenofovir alafenamide will be administered once daily.

BIC/FTC/TAF

Eligibility Criteria

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

You may qualify if:

• Participants with age \>=18 years (or older, if required by local regulations) at the time of obtaining informed consent.
• An individual participant is eligible to participate if they are not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at Screening and a negative urine hCG test at Enrollment) and not lactating.
• Antiretroviral-naïve (no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) person living with HIV.
• Participant (or participant's legally acceptable representative \[LAR\]) is capable of giving written informed consent.
• Eligible participants or their LAR must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrollment of participants who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.
• Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

You may not qualify if:

• Individuals who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates study participation.
• Ongoing or clinically relevant pancreatitis.
• Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
• Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
• History of liver cirrhosis with or without hepatitis viral co-infection.
• Alanine aminotransferase (ALT) \>=5 times the upper limit of normal (ULN) or ALT \>=3\*ULN and bilirubin \>=1.5\*ULN (with \>35% direct bilirubin).
• Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrollment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrollment.
• Participants who, in the investigator's judgment, pose a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
• Signs and symptoms which, in the opinion of the Investigator, are suggestive of active Coronavirus disease 2019 (COVID-19) (example fever, cough) infection within 14 days prior to enrollment.
• Evidence of Hepatitis B virus (HBV) infection based on the results of central lab testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B surface antibody (HBsAb) and HBV Deoxyribonucleic Acid (DNA) as follows:
• a. Participants positive for HBsAg are excluded; b. Participants negative for HBsAb and negative for HBsAg but positive for hepatitis B core antibody (HBcAb) may be excluded based on the following consideration: i. Exclude if HBV DNA is detected \[either \<Lower Limit of Quantification (LLoQ), \>Upper Limit of Quantification (ULoQ) OR numerical value (i.e., between LLoQ and ULoQ)\] ii. Not excluded if HBV DNA is negative, not detected
• Participants with Hepatitis C virus (HCV) co-infection at Screening are eligible only if:
• i. liver enzymes meet entry criteria; and ii. HCV disease is not anticipated to require on-study treatment with any agent(s) that have potential adverse drug-drug interactions (DDIs) with the study interventions; and iii. HCV disease has undergone appropriate work-up and is not advanced and will not require treatment prior to the primary endpoint or later visit. Additional information on participants with HCV co-infection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.
• iv. In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (64)

GSK Investigational Site

Ciudad Autonoma de Buenos Aire, C1425AWK, Argentina

Location

GSK Investigational Site

Córdoba, X5000JJS, Argentina

Location

GSK Investigational Site

Antwerp, 2000, Belgium

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GSK Investigational Site

Brussels, 1000, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Hvidovre, 2650, Denmark

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GSK Investigational Site

Bordeaux, 33000, France

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GSK Investigational Site

Bordeaux, 33076, France

Location

GSK Investigational Site

Lyon, 31059, France

Location

GSK Investigational Site

Montpellier, 34090, France

Location

GSK Investigational Site

Nice, 06202, France

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GSK Investigational Site

Nîmes, 30029, France

Location

GSK Investigational Site

Paris, 75012, France

Location

GSK Investigational Site

Paris, 75013, France

Location

GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Paris, 75970, France

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Cologne, 50668, Germany

Location

GSK Investigational Site

Frankfurt, 60590, Germany

Location

GSK Investigational Site

Hamburg, 20146, Germany

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GSK Investigational Site

München, 80336, Germany

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GSK Investigational Site

Athens, 106 76, Greece

Location

GSK Investigational Site

Athens, 11 527, Greece

Location

GSK Investigational Site

Thessaloniki, 54635, Greece

Location

GSK Investigational Site

Dublin, 7, Ireland

Location

GSK Investigational Site

Dublin, D09 V2N0, Ireland

Location

GSK Investigational Site

Haifa, 31096, Israel

Location

GSK Investigational Site

Ramat Gan, 52621, Israel

Location

GSK Investigational Site

Rehovot, 76100, Israel

Location

GSK Investigational Site

Tel Aviv, 64239, Israel

Location

GSK Investigational Site

Bari, 70124, Italy

Location

GSK Investigational Site

Bergamo, 24127, Italy

Location

GSK Investigational Site

Padua, 35128, Italy

Location

GSK Investigational Site

Pavia, 27100, Italy

Location

GSK Investigational Site

Sassari, 07100, Italy

Location

GSK Investigational Site

Aichi, 460-0001, Japan

Location

GSK Investigational Site

Osaka, 540-0006, Japan

Location

GSK Investigational Site

Tokyo, 108-8639, Japan

Location

GSK Investigational Site

Tokyo, 162-8655, Japan

Location

GSK Investigational Site

Mérida, 97070, Mexico

Location

GSK Investigational Site

Bydgoszcz, 85-030, Poland

Location

GSK Investigational Site

Lodz, 91-347, Poland

Location

GSK Investigational Site

Wroclaw, 50-136, Poland

Location

GSK Investigational Site

Aveiro, 3814-501, Portugal

Location

GSK Investigational Site

Porto, 4099-001, Portugal

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Elche Alicante, 03203, Spain

Location

GSK Investigational Site

La Laguna-Tenerife, 35010, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Marbella, 29603, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07120, Spain

Location

GSK Investigational Site

Palma de Mallorca, 7198, Spain

Location

GSK Investigational Site

Valencia, 46014, Spain

Location

GSK Investigational Site

Stockholm, SE-14186, Sweden

Location

GSK Investigational Site

Basel, 4031, Switzerland

Location

GSK Investigational Site

Zurich, 8005, Switzerland

Location

GSK Investigational Site

Glasgow, G12 OYN, United Kingdom

Location

GSK Investigational Site

London, E9 6SR, United Kingdom

Location

GSK Investigational Site

London, SE5 8AF, United Kingdom

Location

GSK Investigational Site

London, W1D 6AQ, United Kingdom

Location

GSK Investigational Site

London, W2 1NY, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

dolutegravir; Lamivudine; bictegravir; Emtricitabine; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: August 7, 2023
• Study Start: February 9, 2024
• Primary Completion: March 24, 2026
• Study Completion (Estimated): February 23, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

DK (1); JP (4); ME (1); ES (11); DE (5); AR (2); PT (2); IL (4); FR (10); GB (5); SE (1); PL (3); IT (5); IE (2); BE (3); GR (3); CH (2)