[LINK] "Cancer drug shocks HIV out of hiding"

[rfmcdonald]

Not Rocket Science's Ed Yong highlighted a pretty interesting new finding from the realm of HIV/AIDS medical research. The cancer drug vorinostat, it turns out, can disrupt the reservoirs of HIV contained in the white blood cells of infected people, reservoirs which can replenish the infection even after antiretroviral treatments clear the virus from the rest of the human organism. The ability to disrupt these reservoirs means that a drug treatment that could clear HIV infection entirely might be possible.

A team of US scientists led by David Margolis has found that vorinostat – a drug used to treat lymphoma – can [. . . shock] HIV out of hiding. While other chemicals have disrupted dormant HIV within cells in a dish, this is the first time that any substance has done the same thing in actual people.

[. . .]

To see if the drug could do the same for patients, the team extracted white blood cells from 16 people with HIV, purified the “resting CD4 T-cells” that the virus hides in, and exposed them to vorinostat. Eleven of the patients showed higher levels of HIV RNA (the DNA-like molecule that encodes HIV’s genes) – a sign that the virus had woken up.

Eight of these patients agreed to take part in the next phase. Margolis gave them a low 200 milligram dose of vorinostat to check that they could tolerate it, followed by a higher 400 milligram dose a few weeks later. Within just six hours, he found that the level of viral RNA in their T-cells had gone up by almost 5 times.

These results are enough to raise a smile, if not an outright cheer. We still don’t know how extensively vorinostat can smoke HIV out of hiding, or what happens to the infected cells once this happens. At the doses used in the study, the amount of RNA might have gone up, but the number of actual viral particles in the patients’ blood did not. It’s unlikely that the drug made much of a dent on the reservoir of hidden viruses, so what dose should we use, and over what time?

Vorinostat’s actions were also very varied. It did nothing for 5 of the original 16 patients. For the 8 who actually got the drug, some produced 10 times as much viral RNA, while others had just 1.5 times more. And as you might expect, vorinostat comes with a host of side effects, and there are concerns that it could damage DNA. This study could be a jumping point for creating safer versions of the drug that are specifically designed to awaken latent HIV, but even then, you would still be trying to use potentially toxic drugs to cure a long-term disease that isn’t currently showing its face. The ethics of doing that aren’t clear.