Impact of Pitavastatin on Hepatosteatosis as Measured by Computed Tomography in Patients with Human Immunodeficiency Virus - Results from the REPRIEVE trial

• Applicant: Dr. Jana Taron
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 404127893

With 36.7 million people living with the human immunodeficiency virus (HIV) HIV remains the most serious of infectious diseases. Overall survival has drastically improved due to new therapies, however, diseases not related to HIV itself remain largely elevated. Nonalcoholic fatty liver disease (NAFLD) has a prevalence of 30-40% among HIV-infected individuals and has emerged as one of the leading causes of death in this population. This highlights the need for preventive measures in the development of NAFLD in HIV-positive individuals. In this respect, statins, a group of lipid-lowering drugs, has proven particularly suited. A recently conducted study at my host institution (Massachusetts General Hospital/Harvard Medical School) was able to demonstrate the effect of atorvastatin on fatty liver disease in HIV-infected individuals with NAFLD. However, larger randomized studies have been lacking and are critical in determining efficacy and potential adverse effects. With the REPIREVE trial, the largest clinical trial of HIV-related cardiovascular disease, we now have to opportunity to address this pressing question. In this trial, participants are randomized to pitavastatin (a member of the statin drug family which is known to not interfere with the HIV-treatment) or placebo and scheduled for regular study visits. In a mechanistic substudy, 800 subjects additionally receive Computed Tomography (CT) imaging at baseline and after 24 months. We plan to use these images to determine the effects of 2 years of pitavastatin on NAFLD. Liver fat can be easily quantified by measuring liver density on CT images – an established and routinely used method. Changes in liver fat content will then be correlated to the corresponding treatment arm (i.e., pitavastatin or placebo) as well as to the assessed biological factors (i.e., patient characteristics, metabolic parameters, and markers of immune function). This will enable us to evaluate the effect of statin-therapy and gain further insight on potential disease-modulating markers such as the participants` constitution and immune function.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Udo Hoffmann