Research in early HIV infection has pointed investigators towards the gut as a site of initial damage, inflammation, and microbial translocation. Microbial translocation is when bacteria in the gut pass into the general blood stream, contributing to harmful immune activation and inflammation. This makes the gut a potential target for interventional strategies. CTN 257 assessed the impact of HIV infection and ART on mucosal (gut) and circulating immune cells in the early stages of HIV infection.
CTNPT 022b is determining whether a probiotic supplement in combination with ART can help reduce inflammation and harmful immune activation, a potential component of a functional cure. Reducing inflammation may reduce the number of immune cells targeted by HIV for infection and return the gut to a condition of relative health, therefore preserving immune function.
In a recent pilot trial (CTNPT 031), CTN Postdoctoral Fellow Dr. Michaeline McGuinty tested whether vedolizumab, an anti-α4β7 integrin monoclonal antibody currently used to treat inflammatory bowel disease, is effective as a functional cure for HIV. It is believed to work by targeting and preventing CD4 cells from localizing in the lining of the bowel. The project was initiated after a 2016 publication showed that a similar treatment in monkeys induced viral load suppression and maintained CD4 count after stopping antiretrovirals. Presented at CROI 2019, initial results did not show this treatment to be as effective as in the monkey studies. However, vedolizumab did appear to slow down the viral load rebound time and lower the peak viral load rebound after stopping ART. These results suggest that future studies with vedolizumab should investigate a larger dose and longer treatment duration with a greater number of participants. In response to these findings, the CTNPT 031 team added a high-dose arm to the study, which is currently underway.
Dr. Routy and CTN Postdoctoral Fellow Dr. Stéphane Isnard are leading two pilot studies about HIV and gut health. CTNPT 032 is studying the effect of Camu Camu, an Amazonian fruit with antioxidant and anti-inflammatory properties, on the health, microbiota, inflammation and viral reservoir in the gut tissue. In CTNPT 038, they are investigating whether a fecal microbiota transplantation can reduce inflammation and improve gut health in people living with HIV who have a low CD4 count.