Immune activation, HIV persistence, and the cure

Abstract

HIV infection is characterized by persistent immune activation, even in the context of suppressive antiretroviral therapy. This persistent activation, which appears to be fueled by microbial translocation from the gut resulting from HIV-related damage, is associated with deficits in immune function that in turn contribute to persistent activation. The presence of latent HIV reservoirs in lymphoid tissues also provokes immune activation in the context of immune suppression, resulting in expansion of the viral reservoir and potential viral replication, even with suppressive antiretroviral therapy. Therapeutic strategies are being devised to reduce persistent immune activation and limit the size of the HIV reservoir. This article summarizes a presentation by Daniel C. Douek, MD, PhD, at the IAS-USA continuing education program held in San Francisco, California, in March 2013.

Figure 1.

The effects of HIV infection in the gastrointestinal tract. Adapted from Mowat, and Brenchley and Douek.

Figure 2.

The role translocatof microbialion from the gut in fueling immune activation. CMV indicates cytomegalovirus; TCM, central memory T cells; TEM, effector memory T cells. Adapted from Klatt et al.

Figure 3.

Markers of inflammation and gastrointestinal dysfunction that predict mortality in HIV infection. hsCRP indicates high-sensitivity C-reactive protein; iFABP, intestinal fatty acid binding protein; IL, interleukin; KT, kynurenine-to-tryptophan; sCD14, soluble CD14; TNF R1, tumor necrosis factor receptor 1. Adapted with permission from Hunt et al.

Figure 4.

The effects of raltegravir intensification on immune activation (top) and HIV RNA levels (bottom) in peripheral blood mononuclear cells (PBMCs) and gut tissue sites. Adapted from Yukl et al.

Figure 5.

The central role of persistent immune activation in HIV infection. Adapted from Klatt et al.