The Effect of 12 weeks of Mesalamine Therapy on the Endothelial Function of HIV Infected Patients on Highly Active Antiretroviral Therapy
With modern antiretroviral therapy (ART), HIV-infected individuals can now achieve durable viral suppression. Despite this, they continue to have higher rates of many chronic conditions including coronary artery disease and other cardiovascular conditions 2,5 . Persistent immune activation and inflammation, likely mediated by ongoing HIV RNA replication and/or release in lymphoid tissues and persistent microbial translocation 6 , are strong predictors of these complications and have been proposed as important mediators of increased cardiovascular risk 7 . Mesalamine (5-aminosalicylic acid), commonly used for the treatment of ulcerative colitis, decreases gut associated lymphoid tissue (GALT) inflammation in HIV-uninfected individuals. Since the inflammatory microenvironment of the gut may propagate microbial translocation and systemic immune activation, Dr. Peter Hunt is currently conducting a trial of mesalamine in HIV-infected individuals with incomplete CD4+ T cell recovery on suppressive ART to determine whether decreasing the inflammatory microenvironment of the gut reduces microbial translocation and systemic immune activation. We hypothesized that through a similar mechanism, mesalamine might also improve endothelial function in this setting. To address this, we propose adding measures of vascular function as assessed by flow mediated dilation (FMD) of the brachial artery?a strong predictor of cardiovascular disease - to Dr. Hunt's trial. In Aim 1, we will assess the effects of oral mesalamine on brachial artery FMD. In Aim 2, we will assess the relationship between mesalamine-induced changes in soluble markers of endothelial function and FMD. In the parent trial, 30 HIV-infected individuals with incomplete CD4+ T cell recovery despite undetectable plasma HIV RNA levels for at least one year are randomized to either 12 weeks of mesalamine or placebo therapy followed by crossover into the other arm of the study for 12 weeks. Addition of endothelial function measures to the already funded parent trial is a cost efficient approach to studying the impact of mesalamine on cardiovascular risk.