HIV Mutates to Death With New Drug

[via discovery]

HIV is notorious for its ability to mutate and evade drugs designed to destroy it. Now scientists are testing a new drug that actually speeds up that rate of change in the hope that the deadly virus will mutate itself to death.

"The HIV virus is so dependent on mutation that it really lives on the edge of existence," said John Reno, Chief Operating Officer for Koronis Pharmaceuticals, the company developing a drug called KP-1461. "But we figured that if we could increase this mutation rate, [HIV] might finally fall off that edge."

KP-1461 is a mutagen, meaning it encourages mutation, and has been in development for several years by the scientists at Koronis Pharmaceuticals.

When any cell or virus reproduces, there are inevitable mistakes, or mutations, as the four building blocks of DNA pair together into a double helix. Usually, the base adenine pairs up with the base thymine, and one called guanine pairs with cytosine.

KP-1461 looks like both thymine and cytosine, and will occasionally replace one of the normal bases in DNA, causing more errors.

"It really mucks up the genetic information inside the viral DNA," said Reno.

Disrupting HIV's replication doesn't directly destroy the virus, however, at least not immediately. It's the build-up of genetic mistakes that finally destroys it.

That build-up can take time, and could vary depending on the patient and the strain of HIV. The results of the latest Phase Two clinical trial, completed last year with 13 patients, were mixed; some patients saw no drop in their viral load, while others saw a dramatic drop. The scientists are currently working to publish the study results.

What's clear is that KP-1461 does eventually destroy HIV in some patients, unlike the current batch of antiretroviral drugs, which limit the reproduction of the virus but fail to destroy it.

KP-1461 doesn't have any known side effects, but the worry from the Food and Drug Administration is that a drug that induces mutation in a virus could also cause dangerous mutations in the patient's own DNA.

So far it doesn't appear to cause short-term mutations in animal models, but longer-term studies are necessary to eliminate the possibility, said Robert Smith, a professor at the University of Washington who studies other lethal mutagenic drugs.

Mutagenic drugs could be used to fight other diseases as well, such as polio, hepatitis C and influenza. KP-1461 is at the forefront of this new avenue of research.

"Intellectually this is exciting; it's a very creative approach," said Smith. "From a practical perspective, there are still a lot of questions."

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