Mutation: HIV's Achilles' Heel

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The development of HIV drugs is an expensive and a lengthy process.  The AIDS virus, which causes HIV, mutates quickly and regularly, resembling a 'hide-and-seek' scenario making it very difficult to kill with drugs. 

At first glance, this quickly mutating aspect of the virus appears to be advantageous to its growth and ability to spread throughout the body by hiding in the brain and bone marrow, thus inhibiting the human immune system to stop it. 

However, frequent and rapid mutation may actually be HIV's Achilles' heel.  Rather than trying to slow down or prevent the mutations, speeding them up may cause them to kill themselves.

In a new study, Professor Louis Mansky, Director of the Institute for Molecular Virology at the University of Minnesota used drug repositioning, a process whereby a drug approved to treat one condition is used to treat a different condition, to identify clinically approved drugs that have anti-HIV activity.

“HIV has this propensity for rapidly mutating and evolving, and is really in a lot of ways the main reason why there hasn’t been an effective vaccine developed and why there’s continual problems with drug resistance,” reports Mansky.

Researchers identified two drugs that, when combined, may serve as an effective treatment for HIV.  Cancer drugs Decitabine and Gemcitabine were used on HIV in tissue samples in the lab.

“Well, we were specifically looking for drugs that had already been approved by the FDA  for other purposes.  And we were screening to look for ones that may have been overlooked in the past for anti-HIV activity,” says Mansky.

The data,  published in this month's Journal of Virology, reveals that "a combination of the two clinically approved drugs, reduced HIV infectivity by 73% at concentrations that had minimal antiviral activity when used individually.  Decreased infectivity coincided with a significant increase in mutation frequency and a shift in the HIV mutation spectrum." 

Mansky explains, “The drugs do not directly inhibit the virus from replicating.  What they do is to basically cause the virus to elevate its mutation rate.  And through that process, allow it to continue to replicate and basically kill off its infectivity by this process of lethal mutagenesis, which is elevating the mutation rate to the point to where the virus is no longer infectious."

Researchers found that the drugs Decitabine and Gemcitabine were profoundly effective against HIV cultures in lower doses than currently administered for cancer treatment, with no measurable cell toxicity. 

Researchers are currently in the process of converting the drugs into pill form which is how most anti-retroviral drugs are administered. 

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