Study to Evaluate the Efficacy and Safety of a Rilpivarine-based Antiretroviral Tratment Regimen in HIV- Infected Patients With Liver Metabolic Disease Who Maintain Udetectable HIV Viral Load

Fundacion SEIMC-GESIDA63 enrolled

Overview

In HIV-infected people with metabolic fatty liver disease and liver fibrosis of any degree, as measured by non-invasive testing, antiretroviral treatment that includes rilpivinire for 18 months results in a slowing of progression and/or reduction of fatty metabolic liver disease, attenuating inflammation and liver fibrosis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infections Fatty Liver Disease

Interventions

Dolutegravir (DTG) 50 mg/day + Rilpivirine (RPV) 25mg per dayDRUG

DTG/RPV will be administered in combination as 50/25 mg/day tablets or separately as DTG 50 mg/d tablets together with RPV 25 mg/d tablets. There will be no problem if during the course of the study the patient is switched from the combined form to the separate form and vice versa as long as the HAART (Highly Active Antiretroviral Therapy) components are respected.

Tenofovir disoproxil fumarate (TDF) 245 mg per day or Tenofovir alafenamide (TAF) 25 mg per day + Emtricitabine (FTC) 200 mg per day + Rilpivirine 25 mg per dayDRUG

TDF 245 mg/d or TAF 25mg/d together with FTC 200 mg/d and RPV 25 mg/d. They may be administered as single tablets or in combination forms where one tablet contains TDF/TAF and FTC and another RPV tablet. There will be no problem if during the course of the study the patient is switched from the combined form to the separate form and vice versa as long as the HAART components are respected.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients over 18 years of age with HIV infection who have never received antiretroviral treatment with Rilpivirine. * Have a stable ART pattern for at least the last 6 month Exclusion Criteria: * Not having received more than three previous lines of antiretroviral treatment * No resistance mutations that compromise the efficacy of Rilpivirine, Dolutegravir, Tenofovir (TDF and/or TAF) or Emtricitabine. * Have an HIV viral load \< 50 copies/ml for at least the last 6 months, 1 blip below 500 copies/ml is allowed during this period. * Have an ultrasound-diagnosed fatty liver metabolic disease or a CAP (Controlled Attenuation Parameter®) measurement \> 238 dB/m with an IQR \< 30 dB/m. * Have an fatty liver metabolic disease with some degree of fibrosis diagnosed by ET (Fibroscan®) \> 5.2 kPa. In patients in whom ET is not possible, have a FIB-4 \>1.3. * Be able to understand and comply with the requirements and instructions of the protocol. * Understanding long-term commitment to study * Acceptance of their participation in the study by signing an informed consent form. Exclusion Criteria: * Have chronic HBV infection (presence of HBsAg+) or HCV (detectable HCV viral load). Patients with past treated HCV are also not allowed to be included (does not include patients with spontaneously resolved HCV infection). * Have diabetes mellitus on treatment with SGLT2, GLP1 or plioglitazone of less than 6 months duration. * Have a history of alcohol abuse * Harmful alcohol consumption, defined as \>30 grams of alcohol per day in men and \>20 grams of alcohol per day in women. * Have chronic decompensated liver disease, defined as any of the following: presence of encephalopathy, ascites, coagulopathy, oesophageal or gastric varices, or persistent jaundice. * Any previous physical or mental condition (such as habitual drug use) that the investigator believes may interfere with the patient's ability to comply with the study protocol. * Pregnancy or breastfeeding at the screening visit or at any time during the study or intention to become pregnant during the study period. * Prior history of Rilpivirine use of any duration.

Locations (4)

Hospital Universitario Gregorio Marañon

Madrid, Spain

Hospital universitario Infanta Leonor

Madrid, Spain

Hospital Universitario Infanta Sofía

Madrid, Spain

Hospital Universitario La Paz

Madrid, Spain

Outcomes

Primary Outcomes

To evaluate the efficacy of Rilpivirine (RPV) as part of the antiretroviral treatment regimen in VIH-infected people, to slow the progression and/or reduce liver fibrosis of any degree

To measure the no progression and/or regression of liver fibrosis: No change in liver stiffness as measured by ET (Transient Elastography) or FIB4 at the 18-month visit with respect to the baseline, the intervention group (branches 1 and 2) compared to the control group.

Time frame: 18 months

To evaluate the efficacy of Rilpivirine (RPV) as part of the antiretroviral treatment regimen in VIH-infected people, to slow the progression and/or reduce liver fibrosis of any degree

Reduction in liver stiffness measured by ET or FIB4 at the 18-month visit from baseline in the intervention group (arms 1 and 2) versus the control group.

Time frame: 18 months

Secondary Outcomes

Efficacy of RPV in reducing liver fibrosis of any grade

To evaluate the efficacy of RPV in reducing liver fibrosis of any grade, as measured by non-invasive tests, in HIV-infected people: * as part of a nucleoside analogue-free antiretroviral treatment regimen * as part of an antiretroviral treatment regimen that includes tenofovir Proportion of subjects with ET measurement \< 5.2 kPa in the intervention group (arms 1 and 2) compared to the control group at 12 and 18 months from the start of treatment.

Time frame: 12-18 months

Efficacy of RPV in reducing liver fibrosis of any grade

Proportion of subjects with a FIB4 measurement \< 1.3 in the intervention group (arms 1 and 2) compared to the control group at 12 and 18 months from the start of treatment.

Time frame: 12-18 months

Efficacy of RPV in reducing liver fibrosis of any grade

The mean reduction in the APRI measure in the intervention group (arms 1 and 2) versus the control group at 12 and 18 months after the start of treatment.

Data from ClinicalTrials.gov

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Patients who are randomised to this treatment arm will continue with the HAART they were receiving prior to signing the informed consent. As in arms 1 and 2, a change in the form of HAART administration (from a combined to a separate form and vice versa) will be allowed as long as the HAART components are respected.

Time frame: 12-18 months

Efficacy of RPV in reducing liver fibrosis of any grade

Proportion of subjects with an APRI measure \< 0.5 in the intervention group (arms 1 and 2) versus the control group at 12 and 18 months from the start of treatment.

Time frame: 12-18 months