Research Tries ‘Shock and Kill’ to Eliminate HIV

Researchers working on a one-two punch to eliminate HIV say their first punch has landed and they can start working on the second, though plenty of work will be needed on both fronts before a cure is available.

HIV spreads just like other viruses: It takes over a cell’s DNA and uses the cell’s infrastructure to make copies of itself. Most HIV treatments work by blocking new cells from getting infected.

The cells that are actively producing HIV are constantly being killed, either by HIV or by the immune system. So once you stop new cells from getting infected, the patient can achieve a viral load close to zero.

Viral reservoir remains hidden

That’s not a total cure though, because some HIV-infected cells go into a resting state, and stop actively producing the virus. This viral reservoir remains hidden from the immune system. The problem is that if treatment stops, the latent virus will eventually reactivate and the disease will be able to spread again.  

Doctors have gotten pretty good at stopping HIV from infecting new cells, but they still haven’t figured out how to eliminate these reservoirs, and so patients must take medication for their entire life.

That’s why maintaining health care access for everyone living with HIV is a major public health challenge. And even for those who can access life-long care, over time these drugs can damage the liver, kidneys, heart and brain.

‘Shock and kill’

In 2012, a University of North Carolina research group published a proof of concept for a cure called “shock and kill.” They showed that a cancer drug called Vorinostat can “shock” some infected cells into producing HIV again. That brings the virus out of hiding so it can be “killed.”

They described their work in the Journal of Clinical Investigation. “What we did in this study was to determine the optimal dosing regimen — how often the drug should be given — in order to measure consistent reactivation of HIV,” co-author Nancie Archin said to VOA.

Once reactivated, those cells should self-destruct or be killed by the immune system, just like in a typical HIV treatment. But the UNC team’s findings confirm previous evidence showing that isn’t happening.

It’s not yet clear why that is.  

One theory was that Vorinostat was weakening the immune system, so that it wasn’t able to kill the infected cells. But the report ruled that out — relevant parts of the immune system, the study found, were not weakened.

Drug found to be safe

On the bright side, the research demonstrated that Vorinostat is safe to use with HIV-positive patients at doses that can effectively shock cells. The researchers have already begun trials pairing Vorinostat with drugs that might be able to kill the shocked cells. There is a high safety standard for these trials because the participants have their HIV level under control and are generally healthy.

But it’s still not clear if the shock is effective enough if all the reservoir is being activated. The researchers stress that it will likely be a long time before effective treatments are available. And because the treatment involves activating HIV, it will, at least at first, only be available to those who have their viral load under control.

Sharon Lewin, who researches HIV latency at the University of Melbourne and was not associated with this study, told VOA she wished the researchers had used more methods to measure whether the cells were being shocked. “You can measure virus inside the cell and you can measure virus that’s being released from the cell,” she said. “They measure virus just inside the cell.”

It is possible that the cell is producing HIV, but that the HIV virus isn’t leaving the cell. If so, that could explain why the cells aren’t dying.

Treatment successes are few

HIV has been eliminated in a handful of people. At least two infants who received aggressive treatment within hours of contracting HIV never developed viral reservoirs. One man in Germany has been HIV-free for several years following a pair of bone marrow transplants he received during cancer treatment. This has failed in other patients though, and bone marrow transplants are life-threatening procedures.

Lewin said other approaches to eliminating HIV, like editing a person’s genome, or aggressive early treatment, would not be as widely available as a shock and kill approach.

“Those are approaches that will be difficult to roll out to the 37 million people living with HIV,” said Lewin. “An approach that’s just tablets, and tablets that are relatively cheap, that is an approach that could be available.”


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