HIV discovery reveals virus hidden in immune system cells
Cancer-fighting drug romidepsin has been shown to expose hibernating HIV, making it susceptible to attack
The results revealed on Tuesday constitute one of the major scientific discoveries hailed at the Aids 2014 conference in Melbourne, as much of the language shifts away from finding a cure to focusing on big steps in HIV treatment and prevention.
HIV hides in a state of hibernation in CD4 cells, an essential part of the immune system. Yet CD4 cells are unable to fight HIV themselves – that role lies with the immune system’s killer T-cells.
But because killer T-cells can’t detect the HIV hidden within CD4 cells, they are unable to attack and eliminate it from the body. While HIV patients on antiretroviral drug treatment often go on to have undetectable levels of HIV in their system, it is never eliminated.
There is always a reservoir left hiding in cells, undetectable to current screening tools and ready to take hold of the immune system again should patients stop their antiretroviral therapy.
But a research team led by Ole Søgaard at Aarhus University’s department of infectious diseases in Denmark has used the anti-cancer drug romidepsin to activate the virus and bring it out of hiding.
In principle, this means that the killer T-cells should be able to detect the virus, because it leaves a trace on the outside of CD4 cells as it is activated and moves towards the bloodstream, Søgaard said.
“Despite very effective antiretroviral treatment, there is still this reservoir left of HIV cells that are infected but not producing the virus,” he said.
“Once you activate them, these particles will go to the surface and signal to the immune system that this cell is infected and needs to be cleared from the body. So this is a two-step system where we bring the cells to the surface, and then rely on the immune system to kill them.”
In the pilot study, researchers gave six patients three doses of romidepsin over three weeks.
Before each dose, no viral particles were detectable in the patients.
“But after the dose was given we easily measured the virus being released into the plasma in five of these six patients,” Søgaard said.
“We also saw the virus go back to undetectable levels after seven days, so it came up, then hid away again, returning back to a non-active state until the next dose of cancer drug was given.”
However, the researchers found the immune system did not seem to attack the virus after detecting it. Researchers found no significant reduction in the number of infected cells each time the cancer drug brought the virus out of hiding.
“This suggests when you do this reactivation, you also need to also target and activate the immune system and teach it to recognise these cells and attack,” Søgaard said.
“That’s what we’re doing next in this study. We will teach and prime the immune system to recognise HIV before we give patients the cancer drug, and we hope there will be a better chance the immune system can clear those cells when the HIV is reactivated.”
Søgaard emphasised it was unknown how much of the HIV reservoir the immune system would be able to clear even if it could be taught to recognise the virus and attack it. Virus left in just one cell might be enough to allow HIV to thrive again.
“We’re still learning about this disease and where it hides, and it is a really, really tricky disease to cure because it hides in so many places in the body, it hides really well and can hide for an indefinite period of time,” he said.
The difficulty of an HIV cure became particularly apparent with the now famous case of the Mississippi baby, born to an HIV-positive mother.
The child was placed on a strong course of antiretroviral drugs within 30 hours of birth. She continued the treatment for 18 months and when she stopped taking those drugs, she had no detectable virus in her system. It gave hope other infants treated early might be cured.
But 27 months later, the virus was detected and she was placed on antiretroviral drugs again.
In a similar case, two Boston patients received bone marrow transplants that appeared to rid them completely of HIV. They also relapsed, and are now back on antiretroviral treatment.
These cases have been referred to frequently during the AIDS 2014 conference, sometimes brandished as setbacks. But the cases reveal how far HIV treatment has come.
Achieving more than two years without antiretroviral treatment in an infant is unprecedented, especially since the Mississippi baby had no existing immunity to HIV. It has given researchers a new focus on where to fight HIV, as they now know it takes just a tiny amount of dormant virus for HIV to become active again.
The cases have shown that working out exactly where dormant HIV virus resides in the body, and being able to measure it, will be key to future research.
The development of HIV into lethal Aids was once considered inevitable, and less than 30 years after the epidemic began – not a long period in medical science – people living with HIV are able to lead long and healthy lives.
But that all depends on access to treatment, which has the added benefit of protecting against the transmission of HIV during unprotected sex by up to 96%.
The president of the International Aids Society, Françoise Barré-Sinoussi, won a Nobel prize for her role in discovering HIV and said she would not be drawn into talk about how far away a cure for HIV/Aids may be.
“I remember in 1984 someone said we would have a vaccine within two years, and we are now 30 years later,” she said.
“We should move on from this. We will need to collaborate and combine different approaches to HIV – work on cures as well as therapies, prevention and vaccines – and strengthen the relationship between researchers to continue to make progress in tackling HIV.”
This article appeared in The Guardian on July 22, 2014