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 Ant

• Status: Not yet recruiting
• Trial end date: 2026-08-24
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ViiV Healthcare
• Treatments: Dolutegravir; Emtricitabine; Lamivudine; Tenofovir

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Individuals who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.

• Any evidence of a current Centers for Disease Control and Prevention (CDC) Stage 3 disease; with the exception of cutaneous Kaposi's sarcoma not requiring systemic therapy, and CD4+ count <200 cells per cubic millimeter (neither is exclusionary).

• 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.

• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the Investigator and the Medical Monitor for inclusion of the participant prior to enrollment.

• 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 [eitherUpper 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

1. Fib-4 score >3.25 is exclusionary;

2. Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation.

Fibrosis 4 score Formula:

(Age * Aspartate aminotransferase [AST]) / (Platelets * (square root of ALT)

• Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment) are excluded. Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor. Participants who completed treatment at least 7 days prior to Screening are eligible.

• Presence of any major resistance-associated mutations as defined by the International Antiviral Society-United States of America (IAS-USA) resistance guidelines to DTG, 3TC, BIC, FTC or TAF in the Screening result.

• Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent (whichever is longer), prior to first dose of study treatment.

• Treatment with any of the following agents within 28 days of Screening:

i. radiation therapy; ii. cytotoxic chemotherapeutic agents; iii. tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH); iv. immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons.

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

• Treatment with any agent with documented activity against HIV-1 in vitro within 28 days of first dose of study treatment. Treatment withacyclovir/valacyclovir is permitted.

• Participants receiving any protocol-defined prohibited medication and who are unwilling or unable to switch to an alternate medication.

• Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities.

• Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in an interventional clinical trial.

• Participant has estimated creatine clearance <30 milliliter per minute (mL/min) per 1.73 square meter using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R) method.

• Participants known or suspected to have acquired HIV-1 concurrent with use of Pre-exposure prophylaxis (PrEP) or Post-exposure prophylaxis (PEP) must be discussed with the Medical Monitor prior to enrollment.

• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.

• Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.

• Participant is currently participating in, or anticipates being selected for, any other interventional study.