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
- Conditions
- Fatty Liver DiseaseHIV Infections
- Interventions
- Drug: Continue with their previous treatment. Any previous HAART that does not contain Rilpivirine.
- Registration Number
- NCT05898841
- Lead Sponsor
- Fundacion SEIMC-GESIDA
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 75
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TDF 245 mg /day or TAF 25 mg /day + FTC 200 mg /day + RPV 25 mg / day 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 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) Dolutegravir (DTG) 50 mg/day + Rilpivirine (RPV) 25mg per day Dolutegravir (DTG) 50 mg/day + Rilpivirine (RPV) 25mg per day 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) Continue with their previous treatment. Any previous HAART does not contain RILPIVIRINE. Continue with their previous treatment. Any previous HAART that does not contain Rilpivirine. 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.
- Primary Outcome Measures
Name Time Method 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 18 months 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.
- Secondary Outcome Measures
Name Time Method Efficacy of RPV in reducing liver fibrosis of any grade 12-18 months 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.
To evaluate the efficacy of Rilpivirine (RPV) to reduce hepatic steatosis 12-18 months Proportion of subjects with hepatic steatosis measured as TyG score \> 8.38 in the intervention group (arms 1 and 2) compared to the control group at 12 and 18 months from the start of treatment.
To evaluate the efficacy of Rilpivirine (RPV) to decrease the insulin resistance 12-18 months The reduction in the measurement of abdominal circumference and waist ratio/in the intervention group (arms 1 and 2) compared to the control group at 12 and 18 months after the start of treatmen
To evaluate the efficacy of Rilpivirine (RPV) to improve the lipid metabolism 12-18 months Difference in the proportion of subjects with elevated non-LDL cholesterol (value \> 160 mg/dL) in the intervention group (arms 1 and 2) compared to the control group at 12 and 18 months after the start of treatment
To evaluate the efficacy of Rilpivirine (RPV) to decrease the liver inflammation 12-18 months The mean change in AST value (IU/mL) in the intervention group (arms 1 and 2) versus the control group at 12 and 18 months from the baseline visit
To evaluate the efficacy of Rilpivirine (RPV) to decrease the liver inflammation. 12-18 months The change of the gene expression value of: IL1-beta, IL6, IL10, MCP1, PAI-1, TGF-alpha, TNF-alpha in PBMCs in the intervention group (arms 1 and 2) compared to the control group at 12 and 18 months compared to the baseline visit.
Efficacy of RPV to reduce hepatic steatosis/fibrosis. 18 months To assess the efficacy of RPV as part of the antiretroviral treatment regimen in HIV-infected individuals to reduce hepatic steatosis/fibrosis based on the presence of PNPLA3 and MBOAT7-TMC4 genetic polymorphisms.
To characterise the effects of RPV on the expression of inflammatory and fibrogenic markers in peripheral blood mononuclear cells 18 months . Measurement of ALT, AST and GGT in plasma as markers of inflammation.
Efficacy of RPV to reduce the progression to steatohepatitis 18 months In previous studies it has shown that PNPLA3, TM6SF2, and MBOAT7-TMC4 polymorphisms are associated with elevated ALT levels and histologic parameters of nonalcoholic steatohepatitis and fibrosis severity.
On the baseline visit will be collected biological samples for genetuic study. A 3 ml blood sample will be drawn into an EDTA tube at baseline visit for determination of PNPLA3 (C, G alleles) and MBOAT7-TMC4 (G, A alleles) genetic polymorphisms.
Trial Locations
- Locations (4)
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Infanta Sofía
🇪🇸Madrid, Spain
Hospital Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital universitario Infanta Leonor
🇪🇸Madrid, Spain