Cancer drug flushes out lurking AIDS virus: study

Scientists in the United States said Wednesday they had used a cancer drug to flush out the AIDS virus lurking dormant in trial patients’ white blood cells — a tentative step towards a cure.

The ability of the HIV genome, or reproductive code, to hide out in cells and be revived after decades poses a major obstacle in the quest for a cure.

Being able to expose the virus in its hiding place would allow scientists to target the host white blood cells in a killing blitz.

“It is the beginning of work toward a cure for AIDS,” David Margolis, co-author of the study published in the journal Nature, told AFP as the International AIDS Conference was under way in Washington.

HIV is a retrovirus, inserting its DNA into the genome of host white blood cells, CD4+T cells in this case, and turning them into virus factories. Sometimes it goes into hiding in some cells even as others keep on producing.

Some 34 million people around the world are living with HIV, which destroys the immune system and has caused about 30 million AIDS-related deaths since the disease first emerged in the early 1980s.
In the latest study, researchers in the United States used the chemotherapy drug vorinostat to revive and so unmask latent HIV in the CD4+T cells of eight trial patients.

The patients were also on antiretroviral drugs, which stops HIV from multiplying but have to be taken for life because they do not kill the virus hidden away in reservoirs.

“After a single dose of the drug, at least for a moment in time, (vorinostat) is flushing the virus out of hiding,” Margolis said of the trial results — the first drug ever shown to do so.

“This is proof of the concept, of the idea that the virus can be specifically targeted in a patient by a drug, and essentially opens up the way for this class of drugs to be studied for use in this way.”
The drug targets an enzyme that allows the virus to lie latent.

The researchers cautioned that vorinostat may have some toxic effects and stressed this was merely an early indication of feasibility that had to be explored further.

Exactly what would happen after the virus was unveiled in reservoir cells was also not certain, said Margolis.

“We know that many cells that produce HIV die in the process. We know many cells that produce HIV can be identified and killed by the immune system. As far as we can tell, all the viruses floating around while patients are taking therapy don’t get into cells because they are blocked by the therapy,” he said.

Without a host cell, the virus would die within a few minutes.

“There is a possibility that this could work. But … if it is only 99 percent true and one percent of the virus escapes, it won’t succeed. That is why we have to be careful about our work and what we claim about it.”

In a comment published with the study, HIV researcher Steven Deeks said the research provided “the first evidence that … a cure might one day be feasible”.

But, as is common with early clinical trials, the study raised more questions than answers — including ethical concerns about giving potentially toxic drugs to HIV-infected people who are otherwise healthy, he said.

“These data from the lab of David Margolis are genuinely exciting for those exploring pathways to achieving a cure for AIDS,” Oxford University HIV researcher John Frater told AFP, calling for investment in further research.

HIV immunologist Quentin Sattentau called the findings promising, but said other types of reservoir cells, including in the brain, may not respond to this treatment.

“Thus there is a long way to go before we will know if this can work to completely eradicate HIV from an infected person.” mlr/gk