Effect of PCSK9 Inhibition on Cardiovascular Risk in Treated HIV Infection (EPIC-HIV Study)
Atherosclerosis in the setting of HIV infection is distinct and includes increased vascular inflammation, worsened endothelial function, and a predominance of non-calcified plaque. These outcomes can be assessed using specialized noninvasive imaging which strongly predict future CV events in the general population. PCSK9 has emerged as an important pharmacologic target for cholesterol lowering in the general population and recent studies among individuals without HIV have shown that PCSK9 inhibitor therapy is safely tolerated and significantly reduces major CV events in the general population. The investigators will perform a clinical trial of PCSK9 inhibition in the setting of HIV infection. This will be a randomized, placebo-controlled study to evaluate the effects of PCSK9 inhibition on vascular inflammation, endothelial function, and non-calcified plaque using a PCSK9 inhibitor called alirocumab. This study will recruit 140 treated individuals with HIV who are aged 40 and older, with known CVD or risk factors for CVD and who have evidence of vascular inflammation at baseline. The primary and secondary objective of this study is to determine whether PCSK9 inhibition can improve arterial inflammation as assessed by FDG-PET/CT and endothelial function as assessed by flow mediated vasodilation. The investigators will correlate changes in arterial inflammation and endothelial function with lipids and markers of inflammation and immune activation. The tertiary objective is to perform a pilot evaluation of the impact of PCSK9 inhibition on non-calcified plaque as measured by coronary CT angiography. Non-calcified plaque measurements will be correlated with changes in lipid parameters and markers of inflammation and immune activation.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Males and females equal or greater than 40 years of age.
• Documented HIV infection.
• HIV-1 RNA level below 200 copies/mL for at least 12 weeks prior to study entry
• CD4 T Cells ≥200 cells/mm3 at screening
• Continuous ART for at least 12 weeks with no change in regimen prior to study entry.
• Moderate or high CVD risk defined as: documented CVD as assessed by meeting at least 1 of 3 criteria below:
∙ Coronary artery disease (CAD)
‣ Cerebrovascular disease
‣ Peripheral arterial disease
• OR any one of the following CVD risk factors:
‣ Controlled type II diabetes mellitus (HbA1C ≤ 8.0%)
‣ Family history: a first degree relative who had a heart attack, stroke, or documented CVD as defined in the previous section that occurred: a. When they were age 55 years or younger for males (father, uncle, or brother) b. When they were age 60 years or younger for females (mother, aunt, or sister)
‣ Current smoking
‣ Hypertension
‣ Dyslipidemia
‣ A hsCRP ≥ 2mg/L at screening.
• Lipids at screening visit:
‣ Fasting LDL-C ≥ 70 mg/dL (1.81 mmol/L);
⁃ Fasting TG ≤ 600 mg/dL (6.78 mmol/L).
⁃ If subjects meet ACC/AHA criteria for statin therapy and are not currently on a statin, subjects must be taking a stable dose of statin for at least 4 weeks, unless they are statin intolerant, refuse to take a statin, or have a medical condition (e.g. chronic hepatitis) where a statin is contraindicated.