Extended-Release Niacin Versus Fenofibrate in HIV-Infected Participants With Low High-Density Lipoprotein Cholesterol: Effects on Endothelial Function, Lipoproteins, and Inflammation

In individuals infected with human immunodeficiency virus (HIV), low high-density lipoprotein cholesterol (HDL-C) is very common and is associated with disease progression, greater immunosuppression, and immune activation [1]. Antiretroviral therapy (ART) generally increases HDL-C levels; however, HDL-C levels do not return to normal even with prolonged ART. In the Multicenter AIDS Cohort Study, 55% of men had depressed HDL-C levels (<40 mg/dL) after 6–7 years of ART [2]. Depressed HDL-C levels predict future cardiovascular disease (CVD) events in HIV-infected patients [3, 4] and in the general population [5, 6]. However, current guidelines for managing dyslipidemia in the general [7] and in the HIV-infected population [8, 9] do not recommend drug intervention for low HDL-C; they focus on treating elevated levels of low-density lipoprotein cholesterol (LDL-C) and severe hypertriglyceridemia. Indeed, the clinical benefits of HDL-increasing therapies such as niacin and fibrates are not proven. Trials of fenofibrate [10, 11] and niacin [12, 13] among non-HIV-infected participants with well-controlled LDL-C on statins have not demonstrated a benefit on CVD events, and genetic studies have questioned the relationship between HDL-C and CVD risk [14–16]. Extended-release niacin [17–19] and fenofibrate [20, 21] are well tolerated and increase HDL-C and HDL particles in HIV-infected persons. Both drugs also reduce apolipoprotein B [17, 21], non–HDL-C, and triglyceride levels [17, 21, 22]. A pilot study of niacin in HIV-infected individuals [18] suggested that its use improved brachial artery endothelial function. To determine if treatment with extended-release niacin or fenofibrate could improve arterial endothelial function and cardiovascular inflammatory biomarkers, we performed a 24-week, open-label randomized trial in HIV-infected participants with low HDL-C and elevated triglycerides.