Therapeutic Areas

Controlling HIV Resistance

HIV drug resistance is the ability of the virus to mutate and replicate even in the presence of antiviral drugs. The consequences include treatment failure, greater healthcare costs, the imperative to move to alternative treatments, and the spread of resistant strains of HIV to other patients. Thus, there is pressing need to create new drugs for the changing HIV virus. Targeting RNP complexes in HIV give three significant advantages over current classes of HIV drugs:

Disrupting structured viral RNA. Structural RNA forms highly conserved but inherently unstable molecules. The RNA component of an RNP complex is more sensitive to point mutations than genes that encode proteins, thus imposing a high barrier to drug resistance.

Disrupting cooperative assembly of the RNP complexes. Formation of HIV RNP complexes requires the proper assembly of multiple proteins on the RNA. These proteins are highly conserved and the RNA-binding domains are even more invariant suggesting that mutations in these proteins are not tolerated.

Essential proteins encoded in overlapping regions of the HIV-1 genome. By utilizing RNA as a structural component and encoding many essential components in overlapping sequences, the virus has exposed a vulnerable drug target. The HIV genome contains critical RNA structures that overlaps the most highly conserved region of essential genes. Mutations in overlapping regions are more likely deleterious to multiple HIV-1 components and are therefore selected against.