Study subjects are HIV infected patients with BMI>25kg/m2 and who have at least one metabolic syndrome component or a fatty liver disease.
Conditions
Interventions
Trade Name: Isentress
Pharmaceutical Form: Coated tablet
Sponsors
Helsinki University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent (IC) obtained • HIV-positive adult (over 18 years) subjects currently on stable ART, with no changes in the ART regimens during the past 6 months • Current ART includes either a protease inhibitor or efavirenz • No documented or suspected resistance to integrase inhibitors or to NRTIs • No prior history of virologic failure. Failure is defined as a confirmed plasma viral load > 200 cop/ml measured no less than six months after initiation or modification of therapy • Virological blips accepted only if a single viral load measurement has been between 50-200 cop/ml followed by VL 25 kg/m2 and at least one metabolic syndrome condition, which are o BP = 130/= 85 mmHg or hypertension medication currently in use or o fasting glucose = 5.6 mmol/l or B-HbA1C > 42 mmol/mol or diabetes medication currently in use or o HDL 94 cm in men and >80 cm in women (or respective cut off values for non-European ethnic groups as defined by International Diabetes Federation) OR • ultrasound or biopsy proven hepatosteatosis Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: • Within 12 month window period prior to screening, one or more HIV VL measurement of >50 cop/ml • More than one consecutive HIV VL measurements of > 50 cop/ml in the treatment history after initial viral suppression with ART • Chronic hepatitis B or C • Daily alcohol consumption = 30 g for men and = 20 g for women • Pregnancy or planned pregnancy during the study period • Lipid or glucose lowering regimen or hormonal supplement started within 3 months before the planned study start • Psychiatric disorder, which prevents a study subject to understand the study protocol • Other serious disease, which prevents a study subject to participate in the study • For MRI/spectroscopy imaging: metal objects in the body or claustrophobia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the effect of ART switch (a protease inhibitor or efavirenz to raltegravir) on 1. Liver Stiffness 2. Body Composition including subcutaneous and visceral adipose tissue volume 3. Glucose Metabolism 4. Lipid Profile 5. Metabolic and Inflammatory Biomarkers 6. Subcutaneous adipose tissue metabolic gene expression 7.Stool microbiome, saliva and urine 10. Basal metabolic rate. In addition, 8. To collect safety and tolerability data related to the switch to raltegravir. 9. To analyze the fatty liver adipose allele (B-PNPLA3) in this study group. ;Primary end point(s): The change in liver fat content measurered by the proton magnetic resonance spectroscopy after 24 weeks of changing a protease inhibitor or efavirenz to raltegravir versus continuing a protease inhibitor or efavirenz -containing regimen.;Timepoint(s) of evaluation of this end point: Baseline and 24 weeks.;Main Objective: To evaluate the effect of switching from a protease inhibitor or efavirenz to raltegravir on liver fat content. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Baseline to 24-week Change in Body Composition (subcutaneous and visceral adipose tissue volume measured by magnetic resonance imaging), total body fat and lean tissue mass measured by Bioelectrical Impedance Analysis 2.Baseline to 24-week Change in Liver Stiffness measured by transient elastography (Fibroscan ®) 3.Baseline to 24-week Change in Glucose Metabolism including fasting glucose, insulin, 2-h oral glucose tolerance test 4.Baseline to 24-week Change in Lipid Profile (LDL and HDL cholesterol, Triglyceride) 5.Baseline to 24-week Change in Metabolic and Inflammatory Biomarkers (e.g. high-sensitivity C-reactive protein (hsCRP), adiponectin, etc) 6.Baseline to 24-week Change in subcutaneous adipose tissue gene expression (focusing in metabolic and inflammatory gene expression panels) 7.Baseline to 24-week Change in stool and saliva microbiomes 8. Determination of basal metabolic rate by indirect calorimetry at screening and at the end of study 9. Monitoring safety and tolerability throughout the study 10. Determination of the fatty liver adipose allele (B-PNPLA3) ;Timepoint(s) of evaluation of this end point: Baseline and 24 weeks. | — |
Countries
Finland
Contacts
Public ContactDr. Jussi Sutinen
Helsinki University Hospital
Outcome results
None listed