Fatty liver disease in people with HIV infection Digestive System Human immunodeficiency virus [HIV] disease
Conditions
Interventions
The trialists plan to recruit people with well controlled HIV (that is, an undetectable viral load) and evidence of NAFLD on a scan, who attend care at Brighton and Sussex University Hospitals NHS Tru
Sponsors
University Hospitals Sussex NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 02/02/2022: 1. Aged 18 years and older – male or female 2. HIV-1 infected with durably suppressed (=6 months) HIV VL (<50 copies/ml) NB. One HIV VL blip (50-200 copies/ml) is allowed in the 6 months prior to screen 3. Has evidence of NAFLD on hepatic imaging (USS, CT or MRI) or liver biopsy either at screen or in the 6 months prior to screen 4. Provides written, informed consent to participate 5. Is willing to comply with the protocol requirements 6. If female and of child bearing potential, is using effective birth control methods (as agreed by the investigator) and willing to continue practising these birth control measures during the trial and for at least 30 days after the end of the trial. Note: Women who are postmenopausal for least 2 years, women with a total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential 7. If male, and sexually-active with female partners of child bearing potential, is using effective barrier contraception, and willing to continue using this during the trial and for at least 30 days after the end of the trial Previous participant inclusion criteria: 1. Aged 18 years and older – male or female 2. HIV-1 infected with durably suppressed (= 6 months) HIV VL. NB. One HIV VL blip is allowed in the 6 months prior to screen 3. Has evidence of NAFLD on hepatic imaging (USS, CT or MRI) either at screen or in the 6 months prior to screen 4. Provides written, informed consent to participate 5. Is willing to comply with the protocol requirements 6. If female and of child bearing potential, is using effective birth control methods (as agreed by the investigator) and willing to continue practising these birth control measures during the trial and for at least 30 days after the end of the trial. Note: Women who are postmenopausal for least 2 years, women with a total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential 7. If male, and sexually-active with female partners of child bearing potential, is using effective barrier contraception, and willing to continue using this during the trial and for at least 30 days after the end of the trial
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 02/02/2022: 1. Severe cardiovascular disease including known angina or history of myocardial infarction 2. History of postural hypotension, defined as a reduction in the systolic blood pressure of > = 20mmHg after standing for at least one minute 3. Individuals already receiving MVC at screening 4. HIV viral load detectable (one blip within 6 months prior to screen is allowed) 5. Current HCV or HBV (HBcAb-positive, HBsAg-negative is permitted; anti-HCV Ab positive with HCV RNA negative for > = 12 months following treatment or spontaneous clearance is permitted) 6. Other chronic liver disease including but not exclusively: cirrhosis, alcohol-related liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, haemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, non-cirrhotic portal hypertension, drug-induced as deemed by a hepatologist 7. ALT or AST >5x the ULN (where ULN is defined locally as 41 IU/L) 8. Severe renal insufficiency (creatinine clearance = 20mmHg after standing for at least one minute 3. Individuals already receiving MVC at screening 4. HIV viral load detectable (one blip within 6 months prior to screen is allowed) 5. Current HCV or HBV (HBcAb-positive, HBsAg-negative is permitted; anti-HCV Ab positive with HCV RNA negative for > = 12 months following treatment or spontaneous clearance is permitted) 6. Other chronic liver disease including but not exclusively: cirrhosis, alcohol-related liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, haemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, non-cirrhotic portal hypertension, drug-induced as deemed by a hepatologist 7. ALT or AST > 3x the ULN (where ULN is defined locally as 41 IU/L) 8. Severe renal insufficiency (creatinine clearance < 30 mL/min) 9. HIV-2 infection 10. Known allergy or intolerance to MVC or its constituents including hypersensitivity to peanuts or soya 11. If female, pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 02/02/2022: 1. Proportion of eligible individuals approached who are successfully recruited using MACRO electronic case report form at week 96 2. Monthly participant recruitment rate collected by completed CRFS up to recruitment completion 07/01/2020 3. Participant retention collected through eCRF completion in the study at 48 and 96 weeks in the maraviroc and non-maraviroc assigned groups 4. Proportion of participants for whom there is missing data collected by eCRF at 48 and 96 weeks in the maraviroc and non-maraviroc assigned groups 5. Proportion of participants reporting adverse events collected by eCRF at 48 and 96 weeks in the maraviroc and non-maraviroc assigned groups 6. Level of self-reported adherence to the study drug as collected by patient questionnaire at 48 and 96 weeks in those allocated to the maraviroc group Previous primary outcome measure: 1. Proportion of eligible individuals approached who are successfully recruited using MACRO electronic case report form at week 96 2. Monthly participant recruitment rate collected by completed CRFS up to recruitment completion 30/09/2019 3. Participant retention collected through eCRF completion in the study at 48 and 96 weeks in the maraviroc and non-maraviroc assigned groups 4. Proportion of participants for whom there is missing data collected by eCRF at 48 and 96 weeks in the maraviroc and non-maraviroc assigned groups 5. Proportion of participants reporting adverse events collected by eCRF at 48 and 96 weeks in the maraviroc and non-maraviroc assigned groups 6. Level of self-reported adherence to the study drug as collected by patient questionnaire at 48 and 96 weeks in those allocated to the maraviroc group | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. ELF score using ELF blood test at baseline, 48 and 96 weeks 2. Fibroscan stiffness fibroscan test at baseline, 48 and 96 weeks 3. Fibroscan Controlled Attenuation Parameter (CAP) using fibroscan test score at baseline, 48 and 96 weeks 4. % with a CT liver: spleen attenuation ratio <1.0 measured using patient notes and CT of liver at baseline and 96 weeks 5. Blood-derived biochemistry (fasting HDL:chol ratio, LDL, HDL, TG, glucose, plus Hb1AC and ALT) measured using blood test at baseline, 48 and 96 weeks 6. Clinical signs of the metabolic syndrome (BMI, waist circumference and weight) measured at baseline, 48 and 96 weeks 7. HIV parameters (CD4 cell count and % with undetectable HIV VL) measured using a blood test at baseline, 24, 48, 72, 96 weeks 8. Quality of life assessed using the chronic liver disease questionnaire for NAFLD (CLDQ:NAFLD), and the SF-36 and WPAI:SHP questionnaires at baseline, 48 and 96 weeks | — |
Countries
England, United Kingdom
Outcome results
None listed