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Cancer drug vorinostat flushes HIV virus out of hiding, according to recent clinical trial

Scott Hixson

Cancer drug vorinostat flushes out the HIV virus from its dormant state

The finding marks the first step in a search for a cure for AIDS

The cancer drug vorinostat is reported to flush out the HIV virus from its “hiding” places in white blood cells, according to scientists within the U.S. who have said this finding marks the beginning of work to find a cure for AIDS.

The cancer drug is able to expose the virus as it hides dormant in patients’ white blood cells. The ability of the HIV genome, or reproductive code, to remain dormant in cells and revive after decades poses a grave threat to the search for a cure.

Being able to target the virus as it lies hidden within a patient’s white blood cells allows scientists to target the host white blood cells and effectively flush out the virus.

HIV is a retrovirus that inserts its DNA into the genome of host white blood cells, CD4+T cells in this study, and causes the cells to produce more of the virus while some of it may go dormant.

In this recent study, scientists used the chemotherapy cancer drug vorinostat to highlight the HIV virus as it lay dormant in the CD4+T cells of eight trial patients.

The patients were also given antiretroviral drugs, which prevents the HIV virus from multiplying. These antiretroviral drugs must be taken for life as they do not kill the virus that is hidden away lying dormant.

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

“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. As of yet, vorinostat is the first drug ever shown to flush the HIV virus out of hiding.

”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,” Margolis added.

The researchers who conducted the study cautioned that this was simply an early indication and that vorinostat may have some toxic effects.

“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.

“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,” Margolis said of the study.

According to HIV researcher Steven Deeks, the research provides “the first evidence that […] a cure might one day be feasible.”

“These data from the lab of David Margolis are genuinely exciting for those exploring pathways to achieving a cure for AIDS,” said Oxford University HIV researcher John Frater.

As is common with many early clinical trials, the study raised many concerns, including the ethical dilemma of giving a possibly toxic drug to HIV patients as well as whether other types of reservoir cells, including those in the brain, would respond to the vorinostat 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,” said HIV immunologist Quentin Sattentau.

Over 34 million people around the world are infected with the HIV virus, which has caused approximately 30 million AIDS-related deaths since the disease first emerged in the early 1980s.

According to Margolis’ press release, “This work provides compelling evidence for a new strategy to directly attack and eradicate latent HIV infection. Long-term, widespread use of antiretrovirals has personal and public health consequences, including side effects, financial costs, and community resistance. We must seek other ways to end the epidemic, and this research provides new hope for a strategy to eradicate HIV completely from the body.”

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