A Randomized Open-Label Trial Comparing Dolutegravir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide for Maintenance of Virological Suppression in HIV

The primary objective of this clinical trial is to evaluate the efficacy of **DTG/3TC** (Dolutegravir/Lamivudine) for the maintenance of virological suppression in adults with **HIV** infection compared to **BIC/FTC/TAF** (Bictegravir/Emtricitabine/Tenofovir Alafenamide). The study aims to demonstrate the non-inferiority of DTG/3TC versus BIC/FTC/TAF in maintaining virological suppression, with the potential to claim superiority. This is clinically relevant as it may provide an alternative maintenance therapy option for individuals living with HIV, potentially improving patient outcomes and treatment adherence.

Secondary objectives include:

• Evaluating the efficacy of DTG/3TC for maintaining virological suppression compared to BIC/FTC/TAF.
• Assessing changes in weight and BMI from baseline with both therapies.
• Evaluating absolute values and changes from baseline in CD4+ cell count and CD4:CD8 ratio.
• Assessing changes in total and regional fat and fat-free mass.
• Evaluating changes in subcutaneous and visceral fat.
• Assessing changes in lumbar and hip bone mineral density and trabecular bone score.
• Evaluating changes in fasting glucose, insulin, HOMA-IR, HbA1c, plasma lipids, and FIB-4 score.
• Assessing changes in estimated glomerular filtration rate (CKD-EPI) and urinary protein/creatinine.
• Evaluating changes in blood pressure.
• Assessing changes in sleep quality, anxiety, depression, and quality of life at each visit.
• Evaluating the tolerability of DTG/3TC and BIC/FTC/TAF.
• Assessing genotypic resistance mutations in case of viral failure.

The clinical trial involves a study population of adults diagnosed with **HIV** infection, with an age range of 18 years and older. The trial includes both male and female participants, and the sponsor has not provided the total number of participants. The participants are required to have maintained virological suppression, with HIV RNA levels below 50 copies/mL for at least 24 weeks prior to screening. They must be on a regimen for HIV that includes more than one pill a day or a single tablet regimen with specific components for at least 24 weeks before screening. The study population is composed of individuals who are clinically stable and healthy, aside from their HIV condition, as determined by a medical evaluation. Participants are not part of a vulnerable population, and females of childbearing potential must adhere to effective contraception methods. The selection criteria ensure that participants have no history of viral failure or known resistance to the study drugs. Lifestyle factors such as diet and physical activity are not specified in the trial data provided.

The clinical trial is designed to evaluate the efficacy of **DTG/3TC** for the maintenance of virological suppression in adults with **HIV** infection compared to **BIC/FTC/TAF**. This study is an open-label, randomized clinical trial with the objective of demonstrating the non-inferiority of DTG/3TC versus BIC/FTC/TAF, with the potential to claim superiority. The trial is structured to include a series of study visits, beginning with an inclusion (screening) visit, followed by regular follow-up visits, and concluding with an end-of-study visit. The trial is expected to run from June 22, 2021, to January 1, 2025, with recruitment having started on July 14, 2021, and ending on January 31, 2023.

Participants will be involved in the study for a maximum treatment period of 96 weeks. The trial employs a randomized design, ensuring that participants are randomly assigned to receive either the test product, Dovato 50 mg/300 mg film-coated tablets, or the comparator product, Biktarvy 50 mg/200 mg/25 mg film-coated tablets. Both products are administered orally, with a maximum daily dose of one tablet. The study is not a low-intervention trial, as it involves the use of approved and marketed drugs under their usual clinical practice conditions.

The sequence of study visits includes an initial screening to confirm eligibility, which requires participants to have a confirmed **HIV** infection, be at least 18 years of age, and have maintained an **HIV RNA** level of less than 50 copies/mL for at least 24 weeks prior to screening. Participants must also be on a stable antiretroviral regimen. Follow-up visits will monitor the primary endpoint, which is the proportion of patients with plasma **HIV-1 RNA** ≥50 copies/mL, using the FDA Snapshot method with a 4% non-inferiority margin. The end-of-study visit will assess the overall outcomes and any adverse events.

Participants may be terminated early from the study if they exhibit evidence of previous viral failure, known or suspected resistance to the study drugs, or if they do not adhere to the study protocol. Females of childbearing potential must use highly effective contraception throughout the study and for at least four weeks after the last study visit. The trial is conducted in accordance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants.

The clinical trial involves the administration of **Biktarvy** 50 mg/200 mg/25 mg film-coated tablets, which contain the active substances **emtricitabine**, **tenofovir alafenamide**, and **bictegravir**. These tablets are manufactured by Gilead Sciences Ireland Unlimited Company. The pharmaceutical form is a film-coated tablet, and the route of administration is oral. The dosage regimen involves a maximum daily dose of one tablet, with a total treatment period of up to 96 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to Biktarvy, the trial also includes the administration of **Dovato** 50 mg/300 mg film-coated tablets, which contain the active substances **lamivudine** and **dolutegravir sodium**. These tablets are produced by ViiV Healthcare B.V. Similar to Biktarvy, Dovato is administered orally in the form of a film-coated tablet. The dosage is one tablet per day, with a treatment duration of up to 96 weeks. Compliance with the dosing schedule will be closely monitored to ensure adherence to the treatment protocol.

The trial is designed to compare the efficacy of Dovato as a test treatment against Biktarvy, which serves as the comparator. Both treatments are authorized for use in the European Union and are not classified as orphan drugs. The study aims to evaluate the maintenance of virological suppression in adults living with HIV, assessing the non-inferiority and potential superiority of Dovato compared to Biktarvy.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the proportion of patients with plasma **HIV-1 RNA** levels of ≥50 copies/mL, using the FDA Snapshot method with a 4% non-inferiority margin. This endpoint is designed to determine the effectiveness of the DTG/3TC regimen compared to the BIC/FTC/TAF regimen in maintaining virological suppression in adults living with HIV. The trial aims to demonstrate the non-inferiority of DTG/3TC versus BIC/FTC/TAF, with the potential to claim superiority if applicable.