High Dose Atorvastatin Decreases Cellular Markers of Immune Activation Without Affecting HIV-1 RNA Levels: Results of a Double-Blind Randomized Placebo Controlled Clinical Trial

Antiretroviral therapy (ART) has transformed our clinical approach to human immunodeficiency virus (HIV) infection. Despite substantial advances in the management of HIV infection, concerns about transmitted drug resistance, ART-related toxic effects, and the consequences of chronic inflammation persist, emphasizing the need for ongoing research into alternate therapeutic targets and strategies to modulate the chronic immune activation/inflammation observed in this disease [1?3]. Strategies that block key interactions between the host and the virus, including those that target lipid rafts, are an area of interest. Lipid rafts are plasma membrane microdomains rich in sphingolipids and cholesterol that play a critical role in the replication of HIV type 1 (HIV-1) [4, 5]. In vitro models suggest that disruption of lipid rafts with cholesterol-depleting agents, such as 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), reduces HIV-1 particle production [5].
Published in the Journal of Infectious Diseases, v203 p756-764, 2011. Prepared in collaboration with Uniformed Services University, Bethesda, MD; SAIC, Frederick, MD; National Institute of Allergy and Infectious Diseases, Bethesda, MD; Drexel University, Philadelphia, PA; Merck Research Laboratories, North Wales, PA; Pharmaceutical Product Development Inc., Wilmington, DE; and National Cancer Institute, Frederick, MD. The original document contains color images.