The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

16 Feb 2017

Researchers link exhausted immune cells to HIV persistence in the gut

Researchers have uncovered a strong link between a marker of exhaustion of the immune system and HIV persistence in the gut, which could be key to developing new strategies to achieve remission of HIV, or find a way for people living with HIV to safely stop antiretroviral therapy.

Published in the Journal of Infectious Diseases, the study was a collaboration between the Peter Doherty Institute for Infection and Immunity (Doherty Institute), a joint venture of The University of Melbourne and The Royal Melbourne Hospital, and Monash University, University California San Francisco, and the University of Montreal.

Dr Gabriela Khoury, the first author who completed this work as part of her PhD at Monash University said blood, rectal tissue and lymph node biopsies were collected from healthy people living with HIV on effective antiretroviral therapy in San Francisco.

“The patient samples were then sent to Melbourne and Montreal where we carefully measured the amount of virus in hiding and recorded a range of immune markers,” Dr Khoury said.

“We found that a specific marker for an exhausted immune system called PD-1, was present in abundance in the gut, and this correlated with a large amount of HIV hiding in the gut.”

PD-1 plays an important role in keeping the brakes on the immune system, it stops the immune system from responding to a virus like HIV and it may help the virus to remain in hiding.

“We need to find new ways to eliminate virus that hides in people on antiretroviral therapy so it can be recognised by the immune system. One possibility is to block a protein like PD-1, to wake up the virus, and at the same time activate the immune system,” Dr Khoury explained.

University of Melbourne Professor Sharon Lewin, senior author of the study and Director of the Doherty Institute, said the study showed that rectal tissue is an important site for the virus to go into hiding and this might be because of the large number of cells that express the exhaustion marker PD1 in this tissue.

“This discovery provides further evidence that exhaustion of the immune system may be a key part of how the virus manages to hide for years in people with HIV infection on antiretroviral therapy. The rectal tissue seems to be where a lot of the action is happening,” she said.

“New drugs that can reverse immune exhaustion have recently shown to be very effective in treating certain cancers and are now licensed in the US, Europe and Australia. This new immunotherapy, called anti-PD1, may potentially play a role in eliminating HIV too.

“We are very keen to see the effects of these drugs in people living with HIV. These studies are just beginning in the US and Australia in people living with HIV who also have cancer.”