Transcript Harris_presentation

Curing HIV requires overcoming
the virus’s ability to evolve
• There have been many attempts to cure HIV through as
many different mechanisms.
• A common fail point is that HIV is capable of evolving
around a therapeutic mechanism given appropriate
conditions.
• Any cure for HIV must overcome, or even better, utilize,
it’s penchant for change.
• Lethal mutagenesis uses HIV’s genomic promiscuity to
bring it down.
Viral Specificity and Lack of
Cytotoxicity are key in
implementing Lethal Mutagenesis
• In pushing HIV to evolutionary catastrophe, it’s
important to leave the human host unharmed.
• Viral mutagen must be administered in doses low
enough to avoid cytotoxicity.
• Viral mutagen must not be metabolized into a
harmful molecule.
• Viral mutagen must not alter genomic and
mitochondrial DNA.
Progression of Lethal Mutagenesis
has seen the development of more
potent viral mutagens
• Loeb, et. al. used 5’-OH-dC. While it
proved that viral ablation through evolution
was possible, the concentrations of drug
required were near the cytotoxity limit.
• Harris et. al. find in KP-1212 a drug that
can be used in much lower doses with
better results.