Effect on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir
Condition: HIV Seropositivity; Metabolic Syndrome; Fatty Liver
MeSH terms: HIV Seropositivity; Fatty Liver; Metabolic Syndrome; Syndrome
Intervention: Raltegravir
Intervention description: The aim of this study is to investigate whether switching a protease inhibitor (PI) or efavirenz to raltegravir has effect on liver fat and metabolism in HIV-infected patients who are overweight or obese and have at least one metabolic syndrome component .
Intervention MeSH terms: Raltegravir Potassium
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study is a randomized, open, parallel design study.
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will provide data on the switch from a protease inhibitor or efavirenz to the new
      formulation of raltegravir (RAL) dosed once daily. The study group consists of patients with
      metabolic risk factors and co-morbidities, in need of optimization of their current ART to
      minimize the drug-related metabolic side effects as standard of care.

      The primary objective of this study is to investigate whether switching a protease inhibitor
      (PI) or efavirenz to raltegravir once daily reduces liver fat in patients who are overweight
      or obese and have at least one metabolic syndrome component. For this purpose, the liver fat
      content will be analyzed using the proton magnetic resonance spectroscopy.

      In addition, the aim is to clarify the change in the body composition and metabolism in this
      study group. For this purpose the visceral adipose tissue (VAT) and subcutaneous adipose
      tissue (SAT) volumes will be measured and subcutaneous tissue samples will be collected for
      future analyses of adipose tissue function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent (IC) obtained.

          -  HIV-positive adult (age over 18) 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 viral load < 50 cop/ml without the need to initiate a change
             in ART and no blip within 12 month window period prior to screening.

          -  Documented evidence of at least two HIV viral load < 50 cop/ml measurements during the
             past 12 months prior to inclusion: one within 6 months prior to screening.

          -  HIV viral load < 50 cop/ml at screening.

          -  BMI>25 kg/m2 and one metabolic syndrome condition, which are

               -  BP ≥ 130/≥ 85 mmHg or hypertension medication currently in use or

               -  fasting glucose ≥ 5.6 mmol/l or B-HbA1C > 42 mmol/mol or diabetes medication
                  currently in use or

               -  HDL < 1.0 mmol/l in men and < 1.3 mmol/l in women or triglycerides ≥ 1.7 mmol/l
                  or a cholesterol-lowering regimen currently in use or

               -  waist circumference > 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.

        Exclusion Criteria:

          -  Within 12 month window period prior to screening, HIV viral load measurement of >50
             cop/ml.

          -  More than one consecutive HIV viral load 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.