Twisha S Patel, Rustin D Crutchley, Anne M Tucker, Jessica Cottreau, Kevin W Garey

Diarrhea is a common comorbidity present in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) who are treated with highly active antiretroviral therapy. With a multifactorial etiology, this diarrhea often becomes difficult to manage. In addition, some antiretrovirals are associated with chronic diarrhea, which potentially creates an adherence barrier to antiretrovirals and may ultimately affect treatment outcomes and future therapeutic options for HIV. A predominant type of diarrhea that develops in HIV patients has secretory characteristics, including increased secretion of chloride ions and water into the intestinal lumen. One proposed mechanism that may lead to this type of secretory diarrhea is explained by the activation of the cystic fibrosis transmembrane conductance regulator and calcium-activated chloride channels. Crofelemer is a novel antidiarrheal agent that works by inhibiting both of these channels. The efficacy and safety of crofelemer has been evaluated in clinical trials for various types of secretory diarrhea, including cholera-related and acute infectious diarrhea. More recently, crofelemer was approved by the US Food and Drug Administration for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Results from the ADVENT trial showed that crofelemer reduced symptoms of secretory diarrhea in HIV/AIDS patients. Because crofelemer is not systemically absorbed, this agent is well tolerated by patients, and in clinical trials it has been associated with minimal adverse events. Crofelemer has a unique mechanism of action, which may offer a more reliable treatment option for HIV patients who experience chronic secretory diarrhea from antiretroviral therapy.