Probiotics and ARVs

The detrimental effects of chronic immune activation, which is the result of HIV infection, have become increasingly clear. Structural damage to the gut is thought to contribute to this immune activation because of microbial translocation—the leakage of endotoxins and other microbial products across the gastrointestinal barrier and into systemic circulation—but the precise mechanisms driving immune activation, and ways to alleviate among HIV-infected individuals is still not clear.

Two years ago, nonhuman primate studies conducted by Jason Brenchley’s laboratory at the National Institute of Allergy and Infectious Diseases identified a previous unidentified cell in the gut that can produce interleuken-17—a cytokine that is concentrated in mucosal tissues and produced in response to bacterial and fungal antigens. The research showed evidence that in rhesus macaques infected with simian immunodeficiency virus (SIV), the monkey form of HIV, loss of IL-17 producing CD4+ and CD8+ T cells was associated with damage to the colon epithelium and with immune activation (see Monkey Matters, IAVI Report, Nov.-Dec. 2010).

At a March 25 session at the Keystone Symposia’s HIV Vaccines conference, Brenchley presented new data from a study of pigtail macaques chronically infected with the highly pathogenic SIVmac239 strain that suggests probiotics in combination with antiretroviral therapy (ARVs) enhance mucosal immunity and could possibly improve the long-term prognosis of people with HIV.

Probiotic bacteria are live organisms thought to be beneficial to the host, which is why they are often referred to as friendly bacteria. Probiotics are commonly consumed as part of fermented foods with specially added live cultures, such as soy or yoghurt. While yoghurt easily finds its way to the top of healthy menus, it is only recently that researchers have begun to gather scientific data on probiotics and gut health (see A Gut Response to Vaccines, IAVI Report, Nov.-Dec. 2011).

Brenchley said probiotics are considered to be beneficial in the treatment of irritable bowel disease and fatty liver disease.

The monkey study consisted of two arms: one given a daily oral ARV regimen of four different drugs and the other given the same ARV regimen along with a probiotic supplement. Brenchley said after five months the macaques treated with ARVs and probiotics had “enhanced reconstitution” of CD4+ T cells in the colon compared to the ARV-only arm. A biomarker used to measure cell proliferation found a decrease in the activation of CD4+ T cells in the colon of the monkeys given both ARVs and probiotics while a cytokine test found the “overall functionality” of the CD4+ T cells in the colon of the probiotic arm had improved.

Brenchley said the results of the study suggest that supplementing highly active antiretroviral therapy with probiotics might improve the long-term prognosis of HIV-infected individuals.