Scientists have used a new technique to identify the cells inside which the HIV virus remains dormant, in patients treated with antiretroviral therapy. Knowing exactly where the virus is may allow them to "wake up" it up and make sure it is efficiently targeted by the immune system or by therapeutic drugs.
HIV is a worldwide epidemic, affecting around 37 million people across the globe. While antiretroviral therapy (ART) – a drug combination that suppresses the replication of the virus in the body – has improved the outcome for patients, it does not cure them entirely. This is partly due to the fact that HIV can remain in a latent form in different cells of the body, referred to as HIV reservoirs. If an individual discontinues treatment, the virus stops being dormant and the disease can come back in full force.
In the recent study published in the journal Cell Host and Microbes, scientists have implemented an innovative method to reactivate dormant HIV and identify the cells that are hiding it.
HIV is known to live, replicate and remain mostly in CD4+ T lymphocytes, a type of white blood cell. The challenge is to pinpoint where the virus is inside these populations of cells, as they are very diverse.
"CD4+ T lymphocyte populations are highly variable. To develop new, targeted treatments to eliminate these residual infected cells, we need to find exactly where in the CD4 T lymphocyte population the virus hides. Our research has uncovered these HIV hiding places. We were able to identify and quantify the cells containing hidden virus and then test drugs to wake up HIV," says lead author Dr Daniel Kaufmann, from the University of Montreal Hospital Centre (CHUM).
'Waking up' HIV – and killing it
With his team, he developed a technique for detecting HIV reservoirs – one that quickly identifies and examines each individual cell in the body, where the virus remains. The method has been described as a way of taking a "photo" of each individual cell hiding the virus. The scientists say they have thus been able to successfully identify HIV reservoirs in 30 people participating in the study, before and after they started ART.
Once the HIV reservoirs have been found, the idea is that scientists may be able to give patients drugs that can reverse the virus' state of latency. As the virus becomes visible again, the drugs – or the immune system – could target and kill it.
In cell cultures, researchers tested two latency reversal drugs to "wake-up" HIV. These drugs – bryostatin and a derivative of ingenol – were first developed against cancer, but there are suggestions they might also work for HIV.
"In the laboratory we found that the two drugs wake up different populations of CD4+ T lymphocytes, thus waking up different reservoirs. The ingenol derivative activates a population called central memory cells. These cells can live for years in patients, all the while hiding the virus. Therefore, it is particularly important to target these reservoirs," explains co-author Amy Baxter.
The strategy of identifying cells that can hide HIV, in order to wake the virus up and attack it appears to be promising. The next step will be to conduct clinical trials. This will involve testing the two drugs while patient continues taking ART, so that the reactivated virus does not infect other cells.