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.