Biomarkers predict HIV return when treatment is stopped

Melbourne: Scientists have identified biomarkers that can help predict how quickly the HIV virus will return after individuals stop treatment.

Researchers at University of New South Wales, Australia and the University of Oxford believe the research opens up new avenues for understanding why the HIV virus persists in some patients and remains dormant and undetectable in others.

While existing antiretroviral therapy (ART) stops the HIV virus from replicating, it does not completely remove the virus. Destroying the 'hidden' reservoirs of the virus remains one of the 'holy grails' of HIV research.

Previous research has shown the treatment of HIV with ART in the weeks following transmission produces a state of 'post-treatment control' in some patients. However, the mechanisms that induce and maintain this state of remission remain unclear.

Led by Oxford researcher Professor John Frater, the international research team retrospectively analysed data from a randomised study of patients with primary HIV infection involved in the SPARTAC trial.

SPARTAC (Short Pulse Anti Retroviral Therapy at HIV Seroconversion), is the largest randomised controlled trial ever undertaken in primary (recent) HIV infection. The study ran between 2003 and 2011 across eight countries.

In the new study, researchers compared the T-cells of 154 patients in Europe, Brazil and Australia who had their ART treatment interrupted after 12 or 48 weeks.

After coming up with a shortlist of 18 immune system biomarkers, researchers discovered three of them - PD-1,Tim-3 and Lag-3 - were statistically significant predictors of when the virus would rebound.

The researchers found that high levels of these biomarkers, attached to 'exhausted' T-cells prior to patients commencing ART, were associated with earlier rebound of the virus following treatment interruption. This has never been shown before.

Dean of Medicine at UNSW, Professor Rodney Phillips, played an instrumental role in the discovery of the association of the biomarkers with an earlier rebound of the virus.

His 2003 proposal to conduct immunology and virology of the patients receiving ART during the SPARTAC trial, provided researchers with the data they needed to make the discovery 10 years later.

UNSW Kirby Institute's Professor Anthony Kelleher, one of the study's co-authors, said understanding the mechanisms that allow HIV to remain in 'remission' is essential if the virus is to be eradicated.

"We want to be able to predict how the virus will behave before we take patients off ART to test drug therapies aimed at eradicating HIV," Kelleher said.

The study is published in the journal Nature Communications.