Hiding HIV virus 'flushed out' by skin cancer drug

"HIV flushed out by cancer drug", BBC News reports. This headline was prompted by laboratory research showing the promising results of a cancer drug being used to treat HIV.

In the early stages of HIV infection, some of the virus effectively goes into hiding in so-called HIV "reservoirs". These viruses are not "active", so standard anti-HIV drug treatments do not kill them.

In this study, researchers found viruses in blood samples from people with HIV infection could be reactivated using a cancer drug. They believe this would mean the viruses could then be identified by standard drug treatments, and killed. The drug did not appear to be toxic to other blood cells, although it wasn't tested on living humans.

While these are promising results, the experiments are at an early stage and it is not known if it would be safe to use the drug in this way for people infected with HIV.

The drug is currently used on the skin to treat a condition called actinic keratoses, which makes it unclear what effects the drug would have if used internally.  

Where did the story come from?

The study was carried out by researchers from the University of California, the San Francisco Veterans Affairs Medical Center, and Williams College, all in the US.

It was jointly funded by the National Institute of Health, UC Davis Research Investments in Science and Engineering (RISE), the Brazilian Federal Agency, and the Swiss National Science Foundation. Researchers say the funding organisations had no role in the study design, data collection and analysis.

The study was published in the peer-reviewed medical journal PLoS Pathogens.

In general, the media reported the story accurately, but the study's limitations were not fully explained.

The BBC reported an interesting quote from one of the researchers, Dr Satya Dandekar, who said: "We are excited to have identified an outstanding candidate for HIV reactivation and eradication that is already approved and is being used in patients. This molecule has great potential to advance into translational and clinical studies."

But although the drug is being used on patients, it is currently just applied to the skin. The effects may be very different if the whole body is exposed to the drug, as would be required to locate hidden reservoirs of HIV. 

What kind of research was this?

This laboratory study aimed to assess whether a drug currently used to treat a skin condition could be used to reactivate the HIV virus.

Currently available forms of anti-retroviral therapy (ART) are effective in stopping HIV replication, but they do not eliminate "latent" reservoirs of the virus in people infected with HIV. Other studies suggest starting ART early may not prevent latent virus reservoirs forming, or eliminate them.

More recent studies have looked at how some compounds may disrupt the cell signalling pathways that allow HIV to become latent in someone infected with the virus.

Researchers say some of these compounds effectively induce latent HIV reactivation in laboratory settings. One of these compounds is ingenol-3-angelate (PEP005), which is currently approved for clinical use and is used to treat a skin condition called actinic keratoses. This can develop into skin cancer if left untreated.

In this type of study, using cells in a lab, treatments sometimes show positive results, but don't always prove effective in living humans. 

What did the research involve?

The research included a cell culture of latent HIV with "defective" genes. Researchers say this clone is widely used for HIV latency studies.

The researchers collected blood samples from 13 people who were infected with HIV and receiving ART – 12 of these had been on ART for more than three years.

All the individuals had had "suppressed" viral activity for more than six months. The researchers also collected cells from uninfected individuals to act as a control.

All the human and cultured cells were incubated, with compounds being tested for 24 or 72 hours to see whether the cells were dead or alive after the tests.

To determine the potential of PEP005, cells were treated with increasing concentrations of PEP005. 

What were the basic results?

PEP005 increased the reactivation of the cell culture of latent HIV. The effect was even greater when PEP005 was combined with other compounds that also activate latent HIV.

When PEP005 was tested on blood samples from people with HIV infection, it activated latent HIV-infected cells in most of the samples. Again, the effects were higher when PEP005 was used in combination with other compounds.

Researchers also assessed potential side effects of PEP005 and found no significant toxicity or side effects on other blood cells from these samples. 

How did the researchers interpret the results?

Researchers concluded that PEP005 "effectively reactivated HIV from latency in primary CD4+ T cells from HIV-infected individuals receiving ART", and a combination of this and another compound increased this reactivation. They say these results "represent a new group of lead compounds for combating HIV latency". 


This laboratory study found the cancer drug PEP005 may be able to activate latent HIV. This could mean conventional anti-HIV treatments should then be able to eradicate it.

The drug has so far only shown positive results in the laboratory setting and has not been tested on humans in this way. As such, it's too early to tell if this really will help people infected with HIV to be free of the virus for good.

While these are some positive results, the side effects of this drug in humans has not been fully explored.

There is currently no cure for HIV, but there are treatments that can delay the start of symptoms. The World Health Organization (WHO) reports there are 35 million people currently living with HIV globally. Even if effective treatments were available, it's wise to practice safer sex using barrier contraception.

NHS Attribution