Fatty Liver Disease, HIV Infections
Conditions
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.
Interventions
DRUGDolutegravir (DTG) 50 mg/day + Rilpivirine (RPV) 25mg per day
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.
DRUGTenofovir 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
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.
DRUGContinue 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.
Sponsors
Fundacion SEIMC-GESIDA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the efficacy of Rilpivirine (RPV) to reduce hepatic steatosis | 18 months | The mean reduction in the percentage of liver fat, measured by magnetic resonance imaging, which measures the proton density fraction of fat (MRI-PDFF), between the beginning and the end of the study comparing the intervention group (arms 1 and 2) vs control group |
| To evaluate the efficacy of Rilpivirine (RPV) to decrease the insulin resistance | 12-18 months | The mean reduction of the HOMA-IR value 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 improve the lipid metabolism | 12-18 months | The mean reduction in fasting triglycerides (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 ALT value (IU/mL) in the intervention group (arms 1 and 2) vs. the control group at 12 and 18 months from baseline |
| Efficacy of RPV in reducing liver fibrosis of any grade | 12-18 months | 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. |
| 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 | . Analyse the gene expression of inflammatory and fibrogenic markers in peripheral blood polymorphonuclear cells by RT-PCR: IL1-gamma, IL6, IL10, MCP1, P AI-1, TGF-beta, TNF-alpha. |
| 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. |
| 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. |
Countries
Spain
Outcome results
None listed