Evaluation of Doravirine on Hepatic Steatosis and Fibrosis in Asymptomatic HIV Patients: A Pilot Study

The primary objective of this study is to evaluate the impact of a **Doravirine**-based regimen on liver steatosis and fibrosis in asymptomatic individuals with **Human Immunodeficiency Virus** (HIV) who exhibit confirmed liver steatosis (>=S1-238 to 260 dB/m) or liver fibrosis (>=F2->7Kpa). This is assessed through changes in liver steatosis measured by Controlled Attenuation Parameter (CAP) and liver fibrosis measured by transient elastography. The clinical relevance of this objective lies in understanding the potential benefits of Doravirine in managing liver conditions associated with HIV, which could inform treatment strategies and improve patient outcomes.

Secondary objectives include:

• Determining changes in fat liver content by MRI in a subset of 40 participants who switch to a Doravirine-based regimen.
• Assessing changes in lipoprotein particles at week 48.

The clinical trial involves participants diagnosed with **Human Immunodeficiency Virus** (HIV) who are asymptomatic and present with confirmed liver steatosis or liver fibrosis. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically encompass adults. The trial does not involve a vulnerable population. Participants were selected based on the presence of liver steatosis, measured by Fibroscan with a Controlled Attenuation Parameter (CAP) of >=S1-238 to 260 dB/m, or liver fibrosis, with a measurement of >=F2->7 Kpa. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The trial aims to assess changes in liver steatosis and fibrosis, as well as general HIV outcomes and metabolic results, following a switch to a Doravirine-based regimen.

The clinical trial is designed to evaluate the impact of **Doravirine** on liver steatosis and fibrosis in individuals living with **Human Immunodeficiency Virus** (HIV). This study is a low-intervention, randomized, double-blind, controlled trial with an estimated duration of 48 weeks. Participants will be randomly assigned to receive either the test product, Pifeltro 100 mg film-coated tablets, or the comparator product, Delstrigo 100 mg/300 mg/245 mg film-coated tablets, both administered orally. The trial aims to assess changes in liver steatosis and fibrosis using the Controlled Attenuation Parameter (CAP) and transient elastography, respectively, as primary endpoints. Secondary endpoints include the evaluation of fat liver content by MRI and lipoprotein particles at week 48.

The sequence of study visits includes an initial screening visit to confirm eligibility based on the presence of liver steatosis or fibrosis. Participants will then undergo baseline assessments before randomization. Follow-up visits will occur at regular intervals to monitor safety, adherence, and efficacy outcomes. The end-of-study visit will involve comprehensive assessments to evaluate the primary and secondary endpoints. The expected length of participant involvement is approximately 48 weeks, with conditions for early termination including adverse events, non-compliance, or withdrawal of consent.

Inclusion criteria require participants to have confirmed liver steatosis or fibrosis, while exclusion criteria are not specified. The trial is set to commence recruitment on January 1, 2024, with an estimated completion date of May 31, 2025. The study is conducted under the guidelines of the Clinical Trials Regulation, ensuring adherence to ethical and scientific standards.

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**. This medication is administered orally once daily. The pharmaceutical form is a film-coated tablet, and the maximum treatment period is 48 weeks. Participant compliance is monitored through regular follow-ups and adherence assessments.

**Descovy** 200 mg/25 mg film-coated tablets serve as a comparator treatment in the study. This medication comprises the active substances **emtricitabine** and **tenofovir alafenamide**. It is also administered orally once daily in the form of a film-coated tablet, with a maximum treatment period of 48 weeks. Compliance is ensured through similar monitoring methods as the experimental medication.

**Pifeltro** 100 mg film-coated tablets, containing the active substance **doravirine**, are used as part of the experimental regimen. The administration is oral, with a dosage of one tablet per day. The treatment duration is set for 48 weeks, and participant adherence is tracked through scheduled visits and medication logs.

Additionally, **Delstrigo** 100 mg/300 mg/245 mg film-coated tablets are included in the trial. This medication contains **lamivudine**, **doravirine**, and **tenofovir disoproxil** as active substances. It is administered orally once daily, with a treatment period extending up to 48 weeks. Compliance is monitored through regular assessments and adherence checks.

Efficacy in this clinical trial will be assessed by evaluating changes in liver steatosis and fibrosis in people living with HIV (PLWH) who switch to a regimen based on **Doravirine**. The primary endpoints include liver steatosis measured by Controlled Attenuation Parameter (CAP), expressed in dB/m, and liver fibrosis measured by transient elastography, expressed in Kpa. These measurements will be taken at baseline and at week 48 to determine the impact of the treatment regimen.

Secondary endpoints will include the assessment of fat liver content using MRI and the evaluation of lipoprotein particles at week 48. The trial aims to provide insights into the metabolic outcomes and general HIV-related health changes associated with the treatment switch. The study is designed as a low-intervention trial, adhering to the conditions outlined in the Clinical Trials Regulation, and is expected to conclude by May 31, 2025.