Specialty: Hepatology, Primary sub-specialty: Hepatology
Conditions
Interventions
This is an multicentre single arm open label study. All participants have a baseline liver biopsy followed by 48 weeks treatment with Maraviroc in addition to their existing antiretroviral regimen. A
Sponsors
Imperial College of Science, Technology and Medicine
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. HIV-1 infected individuals (males and females) aged 18-75 years 2. Stable antiretroviral therapy for at least one year on a regimen that is unlikely to change in the next 12 months 3. At least two consecutive undetectable HIV viral loads defined by HIV RNA =50 copies/mm3 for at least 6 months prior to the date of inclusion 4. CD4 count = 200 cells/mm3 5. Histological evidence of NASH based on liver histology performed within 12 months prior to visit 1 (Week 0) with a NAFLD activity score (NAS) = 4 with a score of at least 1 in each component (steatosis, lobular inflammation, and hepatocyte ballooning)[26] and <10% weight loss since the time of liver biopsy (see appendix 2 for criteria for offering liver biopsy) 6. Consent to second liver biopsy after 48 weeks treatment with MVC. 7. Patient able to understand and sign a consent form
Exclusion criteria
Exclusion criteria: Liver co-morbidities: 1. Positive HBs antigen (HBsAg) 2. Positive HCV antibody (HCVAb), with the exception of subjects with the presence of HCVAb but negative hepatitis C virus RNA without treatment (i.e. spontaneous clearance following acute infection). 3. Underlying acute or chronic liver disease including non- B non- C viral hepatitis (A & E), autoimmune liver disease, biliary disease, hemochromatosis, Wilson´s disease, alpha-1-antitrypsin deficiency. 4. History of decompensated cirrhosis including ascites, hepatic encephalopathy, or variceal bleeding. 5. Suspicion of drug-related toxicity defined by abnormal LFTs following the recent introduction of a new medication. Additional co-morbidities: 1. Active, serious infections that require parenteral antibiotic or antifungal therapy within 30 days prior to screening visit. 2. Active AIDS-defining disease other than oesophageal candidiasis. 3. Any active life- threatening disease 4. Active malignancy (except for early dysplastic lesions eg anal dysplasia) 5. Congestive cardiac failure 6. Platelet count 1.4 7. Severe renal impairment with CrCl< 30mL/min Lifestyle: Excessive alcohol consumption during the last 6 months prior inclusion defined by more than 14 units/week for women or 21 units/week for men Concomitant medications: 1. Patients actively treated with Maraviroc or having received Maraviroc over the last 12 months. 2. Weight reduction through bariatric surgery in the past 5 years or planned during the conduct of the study. 3. Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents or immunomodulating agents. 4. Receiving any experimental medications within 30 days prior to screening or anticipated use during the trial. 5. Patients receiving pioglitazone, rosiglitazone, vitamin E 800 IU/day, , and/or ursodeoxycholic acid since these drugs may have confounding effect on efficacy of MVC Others 1. Females who are pregnant or breastfeeding 2. Allergy to the study drug or its components (including peanut and soya) 3. Participation in any other clinical trial at Screening without approval from the Sponsor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in the number of hepatic immune cells- including CD3+, CD4+, CD8+, T-bet+, CD56, CD68, CD163 and myeloperoxidase positive cells, identified using immunohistochemistry- in the liver biopsies after 48 weeks of treatment with Maraviroc as compared to baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Improvement in biochemical (fasting glucose, lipids and HOMA index) metabolic parameters at 48 weeks as compared to baseline 2. Modification of circulating inflammatory cytokines, adipokines and markers of macrophage activation (high sensitive IL6, sTNFR1/2, sCD14, sCD163, hsCRP, Leptin, Total and High molecular weight adiponectin) at 48 weeks as compared to baseline 3. Number of subjects with a reduction in the NAS score by =2 points without worsening of fibrosis at 48 weeks as compared to baseline 4. Number of subjects with a reduction in the degree of liver steatosis, inflammation and/or ballooning at 48 weeks as compared to baseline 5. Number of subjects with a reduction of at least one stage of liver fibrosis in patients with fibrosis at 48 weeks as compared to baseline 6. Number of subjects with a reduction of Fibroscan® values and biochemical markers of fibrosis (APRI, Fib-4, NAFLD Fibrosis Score[5]) from at 48 weeks as compared to baseline 7. Number of subjects with normalization of Fibroscan values at 48 weeks 8. Number of subjects with a reduction in liver transaminases (ALT and AST) levels at 48 weeks as compared to baseline | — |
Countries
England, Germany, United Kingdom
Outcome results
None listed