A potential role for fat tissue as an HIV reservoir and source of chronic inflammation

The establishment and persistence of low-grade inflammation in HIV-positive individuals on ART are not well understood. Given that adipose tissue (which makes up between 15 and 20% of the body weight in healthy people) is a source of inflammation in obese individuals, Christine Bourgeois and Olivier Lambotte, from the University Paris SUD, France, and colleagues, decided to investigate a possible role of the adipose tissue in humans infected with HIV and in macaques infected with simian immunodeficiency virus (SIV, an HIV relative that causes AIDS-like disease in some non-human primates).

They found that SIV infection in macaques is associated with changes in the composition of the adipose tissue: Fat tissue from infected animals has higher densities of both adipocytes (fat storage cells) and a mix of differentiated and undifferentiated cells called stromal vascular fraction or SVF that contains a large proportion of immune cells.

Moreover, these immune cells (CD4+ T cells, CD8+ T cells, and macrophages) show enhanced immune activation and/or inflammatory profiles compared with non-infected animals. The researchers were also able to detect SIV DNA and RNA in the combined total SVF as well as in isolated adipose tissue macrophages and CD4+ T cells.

They observed similar results in ART-controlled, HIV-infected patients who had undergone elective abdominal surgery: their SVF samples are positive for HIV DNA, and the researchers could show the presence of infected and virus-producing cells within the patients' adipose tissue and more specifically among adipose CD4+ T cells.

The researchers conclude that they "identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection," and propose that "modulating adipose tissue may constitute a valuable means of limiting both viral persistence and chronic inflammation in ART-receiving HIV-infected patients."