Evaluation of Rilpivirine-Based Antiretroviral Regimen in HIV-Infected Patients with Metabolic Liver Disease Maintaining Undetectable Viral Load

The primary objective of this Phase IV comparative, randomized, open-label pilot study is to evaluate the **efficacy** of Rilpivirine (RPV) as part of an antiretroviral treatment regimen in individuals infected with **HIV** who also have metabolic liver disease. The study aims to determine whether Rilpivirine can slow the progression and/or reduce liver fibrosis of any degree, as measured by non-invasive tests. This is clinically relevant as it addresses the dual challenge of managing HIV while mitigating liver complications, which are common in this patient population and can significantly impact morbidity and mortality.

The clinical trial focuses on **metabolic liver disease** in individuals infected with HIV. The study population includes both male and female participants over the age of 18, who have never received antiretroviral treatment with Rilpivirine. Participants are required to have a stable antiretroviral therapy regimen for at least the last six months, with an HIV viral load of less than 50 copies/ml during this period. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must not have resistance mutations that could compromise the efficacy of Rilpivirine, Dolutegravir, Tenofovir, or Emtricitabine. Additionally, participants should have a diagnosed **hepatic steatosis** with some degree of fibrosis, as measured by non-invasive tests such as ultrasound or Fibroscan®. The trial population was selected based on these criteria, ensuring that participants can understand and comply with the study's requirements and have provided informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, open-label, comparative study to evaluate the efficacy and safety of a **rilpivirine**-based antiretroviral treatment regimen in patients with **HIV** infection and metabolic liver disease. The primary objective is to assess the ability of **rilpivirine** to slow the progression or reduce liver fibrosis, as measured by non-invasive tests. The trial will involve participants who have maintained an undetectable HIV viral load and have not previously received treatment with **rilpivirine**. The study is expected to last for 18 months, with an estimated end date of April 30, 2025.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as having a stable antiretroviral therapy regimen and no resistance mutations to the study drugs. Following the screening, participants will be randomized into different treatment arms. Regular follow-up visits will be conducted to monitor the participants' health status, adherence to the treatment regimen, and any changes in liver fibrosis. The end-of-study visit will occur at the 18-month mark, where the primary endpoint of no progression or regression of liver fibrosis will be evaluated.

The expected length of participant involvement is 18 months, during which they will be required to adhere to the study protocol and attend all scheduled visits. Conditions that may lead to early termination from the study include non-compliance with the study protocol, development of resistance mutations, or any adverse events that compromise the safety of the participant. The trial will utilize **oral** administration of the study drugs, which include **dolutegravir sodium**, **rilpivirine hydrochloride**, **emtricitabine**, and **tenofovir** derivatives, all in the form of film-coated tablets. The study aims to provide valuable insights into the management of metabolic liver disease in HIV-infected individuals using a **rilpivirine**-based regimen.

The clinical trial involves the administration of several **antiretroviral** medications, each provided in the form of film-coated tablets. The primary experimental medication is **Juluca**, which contains **dolutegravir sodium** and **rilpivirine hydrochloride**. Juluca is administered orally at a dosage of 50 mg/25 mg once daily. The maximum treatment period is 18 months, with a maximum daily dose of one tablet. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

Another treatment used in the study is **Emtricitabine/Tenofovir disoproxil Tillomed**, which contains **emtricitabine** and **tenofovir disoproxil**. This medication is also administered orally in the form of film-coated tablets at a dosage of 200 mg/245 mg once daily. The treatment duration and dosing schedule are consistent with the other medications in the trial.

**Truvada** is another comparator treatment, containing **emtricitabine** and **tenofovir disoproxil fumarate**. It is provided as film-coated tablets with a dosage of 200 mg/245 mg, administered orally once daily. The treatment period and monitoring procedures are aligned with the study protocol.

**Descovy** is included in the trial, comprising **emtricitabine** and **tenofovir alafenamide**. The film-coated tablets are administered orally at a dosage of 200 mg/25 mg once daily. The treatment duration is up to 18 months, with compliance monitored throughout the study.

**Eviplera** is another medication used, containing **emtricitabine**, **tenofovir disoproxil**, and **rilpivirine**. It is administered as film-coated tablets at a dosage of 200 mg/25 mg/245 mg once daily. The administration route and monitoring are consistent with the other treatments.

**Tivicay**, containing **dolutegravir sodium**, is also part of the trial. It is provided as film-coated tablets with a dosage of 50 mg, taken orally once daily. The treatment period and compliance monitoring are in line with the study's requirements.

**Odefsey** is included, comprising **emtricitabine**, **tenofovir alafenamide**, and **rilpivirine**. The film-coated tablets are administered orally at a dosage of 200 mg/25 mg/25 mg once daily. The treatment duration and monitoring procedures are consistent with the study protocol.

Finally, **EDURANT**, containing **rilpivirine**, is administered as film-coated tablets at a dosage of 25 mg once daily. The administration route and monitoring are consistent with the other treatments in the trial.

The efficacy of the antiretroviral treatment regimen containing **Rilpivirine** will be assessed in a clinical trial involving HIV-infected patients with metabolic liver disease. The primary endpoint for evaluating efficacy is the progression or regression of liver fibrosis, which will be measured using non-invasive tests. Specifically, the trial will assess changes in liver stiffness as measured by transient elastography (TE) or the FIB-4 index at the 18-month visit compared to baseline. The intervention group (arms 1 and 2) will be compared to the control group to determine any differences in liver stiffness changes.