Evaluation of Safety and Efficacy in Switching from Dolutegravir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in HIV Patients with Neuropsychiatric Vulnerabilities

The primary objective of this Phase IV, randomized, multicenter, double-blind clinical trial is to evaluate the **safety** of switching from the antiretroviral regimen of Dolutegravir/Lamivudine (DTG/3TC) to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) in individuals with HIV who have good virological control and neuropsychiatric vulnerabilities. This is clinically relevant as it aims to ensure that the new regimen does not compromise patient safety, particularly in a population with specific vulnerabilities.

Secondary objectives include:

• Assessing the desirability of switching to BIC/FTC/TAF versus continuing treatment with DTG/3TC.
• Evaluating the efficacy of switching to BIC/FTC/TAF compared to continuing with DTG/3TC.
• Exploring brain integrity and functionality before and after switching to BIC/FTC/TAF.

The clinical trial involves **adult** participants over the age of 18 who have been diagnosed with **HIV** using standard microbiological techniques. The study population includes both male and female subjects, with no vulnerable populations selected. Participants are required to be on active antiretroviral treatment with DTG/3TC and must have a documented HIV viral load of less than 50 copies/mL within the six months prior to the screening visit. Additionally, participants may have a prior clinical diagnosis of insomnia, anxiety disorders, or depressive disorders, as confirmed by a qualified specialist physician. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is a **randomized**, double-blind, controlled study designed to evaluate the safety and appropriateness of switching from a regimen of dolutegravir/lamivudine (DTG/3TC) to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in individuals diagnosed with **HIV** who have good virological control and neuropsychiatric vulnerabilities. The trial is set to run from September 27, 2022, to May 2, 2024, with an estimated duration of 300 days for each participant. The study involves a series of visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, current antiretroviral treatment, and recent HIV viral load measurements. Participants must have a viral load of less than 50 copies/mL and a prior clinical diagnosis of insomnia, anxiety disorders, or depressive disorders.

Following the screening, participants will be randomly assigned to either continue their current DTG/3TC treatment or switch to BIC/FTC/TAF. The trial includes regular follow-up visits to monitor the safety and efficacy of the treatment, with primary endpoints focusing on the proportion of neuropsychiatric adverse effects graded 2-4, as defined by the AIDS Clinical Trials Group Adverse Events Grading Score. Secondary endpoints include the proportion of adverse effects leading to antiretroviral therapy (ART) discontinuation and the proportion of ART discontinuations for any reason. The end-of-study visit will assess the overall outcomes and gather final data on the safety and effectiveness of the treatment switch.

Participant involvement is expected to last for the full duration of the trial unless early termination is warranted. Conditions for early termination include significant adverse effects, withdrawal of consent, or any other medical reasons deemed necessary by the study investigators. The trial aims to provide valuable insights into the management of HIV in patients with neuropsychiatric conditions, ensuring that the switch to BIC/FTC/TAF is both safe and beneficial for this specific population.

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 300 days. The active substances are of chemical origin, and the product is not a paediatric formulation. Participant compliance with the dosing schedule is monitored throughout the trial.

In addition to the experimental treatment, the study includes a comparator treatment using **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. and are also administered orally. The dosage for Dovato is similarly set at one tablet per day, with a treatment duration of up to 300 days. The active substances in Dovato are also of chemical origin, and the formulation is not intended for paediatric use. Compliance with the administration schedule is similarly monitored to ensure adherence to the study protocol.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint focuses on the proportion of **neuropsychiatric adverse effects** graded 2-4, as defined by the AIDS Clinical Trials Group Adverse Events Grading Score11. Secondary endpoints include the proportion of grade 2-4 adverse effects, the proportion of antiretroviral therapy (ART) discontinuations due to neuropsychiatric adverse effects, and the proportion of ART discontinuations for any reason. These endpoints will be measured and analyzed to determine the safety and appropriateness of switching from DTG/3TC to BIC/FTC/TAF in individuals with HIV who have good virological control and neuropsychiatric vulnerabilities. The trial is designed as a Phase IV, randomized, multicenter, double-blind study, ensuring rigorous assessment of the treatment's efficacy and safety.