Evaluation of Safety, Pharmacokinetics, and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Patients Transitioning from Cabotegravir/Rilpivirine

The primary objective of this Phase 4 study is to assess the **safety** of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed participants who are unable or unwilling to continue on cabotegravir and rilpivirine (CAB+RPV) intramuscular injections or who wish to switch to oral therapy through Week 12. This is clinically relevant as it addresses the need for alternative oral treatment options for individuals with HIV-1 infection who may face challenges with injectable therapies.

Secondary objectives include:

• Assessing the pharmacokinetics of bictegravir (BIC), CAB, and RPV after switching to B/F/TAF from CAB+RPV.
• Evaluating the efficacy and persistence of B/F/TAF after switching from CAB+RPV.
• Assessing the safety of B/F/TAF after switching from CAB+RPV through Week 24.
• Evaluating treatment satisfaction of switching to B/F/TAF from CAB+RPV.

The clinical trial involves a total of **25 participants** diagnosed with **HIV-1 infection**. The study population includes both male and female subjects, aged 18 years and older, who are virologically suppressed and currently receiving cabotegravir and rilpivirine (CAB+RPV) intramuscular injections. Participants were selected based on their ability to understand and provide written informed consent, and their willingness to switch to an oral therapy regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). The trial does not include a vulnerable population. Participants are required to have adequate renal function and normal hepatic transaminase levels, and those assigned female at birth must adhere to specified contraceptive methods if engaging in heterosexual intercourse. The selection criteria ensure that participants have no documented resistance to the study drugs and are able to comply with all study requirements.

The clinical trial is designed to evaluate the **safety**, pharmacokinetics, and efficacy of switching to **bictegravir/emtricitabine/tenofovir alafenamide** (B/F/TAF) in participants with **HIV-1 infection** who are virologically suppressed and unable or unwilling to continue with cabotegravir and rilpivirine (CAB+RPV) intramuscular injections. This is a Phase 4, randomized, double-blind, controlled trial with an estimated duration of 24 weeks. The trial will commence with a screening visit to assess eligibility based on inclusion criteria such as age, renal function, and virological suppression status. Participants must be 18 years or older, with documented plasma HIV-1 RNA levels below 50 copies/mL for at least six months prior to the screening visit.

Following the screening, eligible participants will be randomized to receive B/F/TAF orally. Study visits are scheduled at baseline (Day 1), and follow-up visits will occur at Weeks 4, 12, and 24. The primary endpoint is the proportion of participants experiencing treatment-emergent Grade 3 or 4 adverse events through Week 12. Secondary endpoints include plasma concentrations of BIC, CAB, and RPV at specified intervals, and changes in HIV treatment satisfaction scores. The end-of-study visit will occur at Week 24, where final assessments will be conducted.

Participant involvement is expected to last approximately 24 weeks, with conditions for early termination including non-compliance with study requirements, withdrawal of consent, or the occurrence of significant adverse events. The trial aims to provide valuable insights into the safety and efficacy of B/F/TAF as an alternative oral therapy for individuals transitioning from CAB+RPV injections.

The clinical trial involves the administration of **Biktarvy** 50 mg/200 mg/25 mg film-coated tablets, which is an **antiretroviral** medication. The active substances in Biktarvy include **emtricitabine**, **tenofovir alafenamide**, and **bictegravir**. These components are chemically synthesized and are combined in a single pharmaceutical form, a film-coated tablet. The medication is administered orally. Participants in the trial will receive the medication as a single daily dose. The maximum treatment period for this study is 24 weeks. The trial aims to evaluate the safety, pharmacokinetics, and efficacy of Biktarvy in participants who are virologically suppressed and are transitioning from injectable cabotegravir and rilpivirine (CAB+RPV) to oral therapy.

In this study, no non-experimental treatments such as a placebo or comparator treatment are utilized. The focus is solely on the administration of Biktarvy as the experimental medication. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment regimen. The trial is designed to assess the safety of switching to Biktarvy in participants who are unable or unwilling to continue with CAB+RPV intramuscular injections or who prefer to switch to an oral therapy regimen.

Efficacy in this clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include the proportion of participants experiencing treatment-emergent Grade 3 or 4 study drug-related adverse events (AEs) and laboratory abnormalities through Week 12. Secondary endpoints will evaluate plasma concentrations of **bictegravir** (BIC), cabotegravir (CAB), and rilpivirine (RPV) at Day 1, Week 4, 12, and 24, as appropriate. Additionally, the proportion of participants with HIV-1 RNA levels ≥ 50 copies/mL at Weeks 12 and 24 will be measured, with missing data being excluded and discontinuation considered as failure. The number and proportion of participants discontinuing B/F/TAF by Weeks 12 and 24 will also be recorded, along with the proportion experiencing treatment-emergent Grade 3 or 4 laboratory abnormalities through Week 24. Furthermore, changes in HIV treatment satisfaction, as measured by the HIVTSQc score, will be assessed at Week 4.