Evaluation of Efficacy, Safety, and Tolerability of Switching from Bictegravir/Emtricitabine/Tenofovir Alafenamide to Dolutegravir/Lamivudine in Virologically Suppressed HIV Patients Aged 50+

The primary objective of this study is to evaluate the **maintenance of virologic suppression** at Week 48 following a switch from a bictegravir/emtricitabine/tenofovir alafenamide regimen to a dolutegravir/lamivudine (DTG/3TC) single tablet regimen in individuals aged 50 years and older living with **human immunodeficiency virus (HIV)** who are virologically suppressed. This is clinically relevant as maintaining virologic suppression is crucial for preventing disease progression and improving long-term health outcomes in individuals with HIV.

Secondary objectives include:

• Evaluating the **antiviral activity**, immunologic effects, and incidence of disease progression, including HIV-associated conditions, AIDS, and death, over time with DTG/3TC.
• Assessing **viral resistance** in participants experiencing protocol-defined virologic failure over time.
• Evaluating the **safety and tolerability** of DTG/3TC over time.

The clinical trial involves a total of **118 participants** diagnosed with **Human immunodeficiency virus (HIV)**. The study population includes both male and female adults, with an age requirement of at least 50 years at the time of obtaining informed consent. Participants are required to have a documented plasma HIV-1 RNA level of less than 50 copies/mL within three months prior to screening and must have been on uninterrupted antiretroviral therapy (ART) for at least one year. Additionally, they must have been on a regimen of BIC/FTC/TAF for at least six months prior to screening. The trial population was selected based on these criteria, ensuring that participants have no known prior regimen switches due to documented virologic failure. The study does not specify any particular lifestyle considerations such as diet or physical activity. Participants are required to be capable of providing written informed consent, and the trial includes a vulnerable population. The sponsor has not provided further details regarding the general health status or additional lifestyle factors of the participants.

The clinical trial is a **Phase 3b**, multicenter, single-arm, open-label study designed to evaluate the efficacy, safety, and tolerability of switching to a single tablet regimen of **dolutegravir/lamivudine** administered once daily from a **bictegravir/emtricitabine/tenofovir alafenamide** regimen in individuals living with **human immunodeficiency virus (HIV)** who are at least 50 years old and virologically suppressed. The trial aims to maintain virologic suppression at Week 48 post-switch. The study is expected to last until January 31, 2026, with recruitment starting on November 13, 2023.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, virologic suppression, and treatment history. The inclusion criteria require participants to have been on uninterrupted antiretroviral therapy (ART) for at least one year and on the bictegravir/emtricitabine/tenofovir alafenamide regimen for at least six months prior to screening. The primary endpoint is the proportion of participants with plasma HIV-1 RNA ≥ 50 copies/mL at Week 48, assessed using the Snapshot algorithm. Secondary endpoints include virologic suppression at Weeks 24, 48, and 96, changes in CD4+ cell count, and the occurrence of adverse events.

Participants will be involved in the study for a maximum of 96 weeks, with regular follow-up visits to monitor virologic suppression, safety, and tolerability. The end-of-study visit will conclude the participant's involvement, unless early termination is warranted due to adverse events, lack of efficacy, or withdrawal of consent. The trial is not categorized as low intervention, and participants must provide written informed consent before any protocol-specified assessments are conducted. The study is conducted in accordance with local legal and regulatory requirements, ensuring the safety and well-being of all participants.

The clinical trial involves the administration of **Dovato** 50 mg/300 mg film-coated tablets, which contain the active substances **lamivudine** and **dolutegravir sodium**. These tablets are manufactured by VIIV Healthcare B.V. and are administered orally. The dosage consists of one tablet taken once daily. The maximum treatment period for this regimen is 96 weeks. The pharmaceutical form is a film-coated tablet, ensuring ease of ingestion and protection of the active ingredients. Participant compliance is monitored through regular follow-ups and adherence assessments.

In addition to the experimental treatment, the study includes a comparator treatment using **Biktarvy** 50 mg/200 mg/25 mg film-coated tablets. This medication contains the active substances **emtricitabine**, **tenofovir alafenamide**, and **bictegravir**, and is produced by Gilead Sciences Ireland UC. Similar to Dovato, Biktarvy is administered orally, with a dosage of one tablet per day. The maximum treatment period for Biktarvy is 6 weeks. The pharmaceutical form is also a film-coated tablet, designed to maintain the stability and efficacy of the active compounds. Compliance with the dosing schedule is ensured through routine monitoring and participant education.

The efficacy of the clinical trial will be assessed by evaluating the maintenance of virologic suppression in participants who switch from a bictegravir/emtricitabine/tenofovir alafenamide regimen to a dolutegravir/lamivudine (DTG/3TC) single tablet regimen. The primary endpoint for efficacy is the proportion of participants with plasma **HIV-1 RNA** levels of 50 copies/mL or higher at Week 48, as determined by the Snapshot algorithm. Secondary endpoints include the proportion of participants with plasma HIV-1 RNA levels of 50 copies/mL or higher at Weeks 24 and 96, as well as those with levels below 50 copies/mL at Weeks 24, 48, and 96. Additionally, changes in CD4+ cell counts and CD4:CD8 ratios from baseline will be measured at these timepoints. The occurrence of disease progression, including HIV-associated conditions, AIDS, and death, will also be monitored through Weeks 24, 48, and 96.

Data collection will involve regular monitoring of plasma HIV-1 RNA levels and CD4+ cell counts at specified intervals. The occurrence of viral resistance in participants meeting confirmed virologic withdrawal criteria will be assessed over time. Safety and tolerability will be evaluated by recording non-serious adverse drug-related reactions, all serious adverse events (SAEs), and the proportion of participants who discontinue treatment due to adverse events (AEs). The trial is designed to ensure comprehensive assessment of the efficacy and safety of the DTG/3TC regimen in maintaining virologic suppression in the target population.