Attacking HIV in the Gut

Dr. Mirko Paiardini

Dr. Mirko Paiardini

Most research approaching an HIV cure has centered on T cells in the blood. This is understandable, given ready access to such samples. But it is now apparent that, both in HIV-infected humans and in SIV-infected monkey models, one of the very first immunologic events early after infection is severe depletion in the intestines of certain specialized T cells, Th17 and Th22. These cells are recognized by their production of two immune hormones, the interleukins IL-17 and IL-22, respectively. Writing in the February issue of the journal PLoS Pathogens, amfAR-funded scientist Dr. Mirko Paiardini of Emory University, together with colleagues there and at the University of Montreal, report on the function of these cells and the ability of antiretroviral therapy to maintain the cells’ function after infection.

The researchers found that these cell types in healthy monkeys and humans produced at least five critical cytokines necessary to maintain integrity of the intestinal lining. The level of their depletion after an SIV infection in their experimental monkey model directly correlated with levels of immune activation, established early after an infection. Following treatment with ART, improvement in terms of Th17 T-cell number and function inversely correlated with levels of virus in the animal’s blood. In other words, the higher the level of virus, the less recovery there was in the function of IL-17-producing cells. On the flipside, more of those intact cells predicted less of the virus.

Of great significance for studies of potential HIV cures, it was found that after stopping ART in the infected monkeys—as would be done as part of an analytic treatment interruption, or ATI (to help establish that an individual with no detectable virus after an experimental cure trial was truly virus-free)—both Th17 and Th22 T cells were rapidly and severely damaged.

The authors concluded that it was important to preserve intestinal T17 and T22 T-cell function during HIV infection. They emphasized the need for “therapeutic strategies aimed at improving these cells’ function in future HIV cure research.”