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 (MAFALDA-R)

Fundacion SEIMC-GESIDA

Status and phase: Active, not recruiting; Phase 4

Conditions: HIV Infections; Fatty Liver Disease

Treatments: Drug: Dolutegravir (DTG) 50 mg/day + Rilpivirine (RPV) 25mg per day; Drug: Continue with their previous treatment. Any previous HAART that does not contain Rilpivirine.; Drug: 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 day

Study type: Interventional

Funder types: Other

Identifiers

NCT05898841

GESIDA 12422

Details and patient eligibility

About

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.

Enrollment: 75 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 3 patient groups

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

Experimental group

Description:

Dolutegravir (DTG) 50 mg/day + Rilpivirine (RPV) 25mg per day. They may be administered in combination as 50/25 mg/day tablets (Juluca 50/25) or separately as Dolutegravir 50 mg/d tablets together with Rilpivirine 25 mg/d tablets (Tivicay 50 + Edurant 25)

Treatment:

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

TDF 245 mg /day or TAF 25 mg /day + FTC 200 mg /day + RPV 25 mg / day

Experimental group

Description:

Tenofovir disoproxil fumarate (TDF) 245 mg per day or Tenofovir alafenamide (TAF) 25 mg per day + Emtricitabina (FTC) 200 mg/d + Rilpivirina (RPV) 25 mg/d. They may be administered as single tablets (EVIPLERA 200 mg/25 mg/245 mg) or in combination forms where one tablet contains TDF/TAF and FTC and another RPV tablet (TDF/FTC + Edurant 25 or Descovy 25/200 + Edurant 25)

Treatment:

Drug: 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 day

Continue with their previous treatment. Any previous HAART does not contain RILPIVIRINE.

Active Comparator group

Description:

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.

Treatment:

Drug: Continue with their previous treatment. Any previous HAART that does not contain Rilpivirine.