Potential HIV Cure Under Investigation

New treatments for HIV infection are desperately needed.

Fortunately, researchers have now identified a step in the infectious process that seems promising.

HIV integrase undergoes small ubiquitin-like modifier cleavage before it is able to incorporate its viral nucleic acids into the host genome. This process is an emerging and different target for drug therapy.

The journal Scientific Reports recently published a study documenting the novel small ubiquitin-like modifier protease inhibitor drug class in its December 2015 issue.

Small ubiquitin-like modifier protease inhibitors use a mechanism that has no effect on the virus’s cellular entry or the initial intracellular production of virions. In other words, the virus still enters the cell and produces virions.

This drug class targets a host factor, not a viral factor, so the host genome would have to mutate in order for the virus to become resistant. The protein involved is a human protein; therefore, it is unlikely to mutate during the course of an infection compared with a viral protein.

The researchers exposed peripheral blood mononuclear cells to HIV virions and determined the viral count at 4, 7, 10, 12, and 15 days post-infection.

The protein content of the virions was determined through polyethylene glycol concentration, centrifugation, and western blot analysis.

The prototype member of the drug class inhibits the removal of small ubiquitin-like modifier moieties, causing the release of modified virions and curtailing the spread of virions within the body (eg, infectivity).

Over 8 weeks, the researchers saw no drug resistance develop. The prototype small ubiquitin-like modifier protease inhibitors employed did not induce resistance when HIV was exposed to a known protocol to induce AZT and raltegravir resistance.

Modification to small ubiquitin-like modifiers affected neither enzymatic activity nor integrase nuclear localization. Theoretically, any process that might lead to resistance would produce a similar result as the drug mechanism itself.

Virions that develop a mutated integrase site would critically compromise their reproductive fitness.

The study authors noted that this drug class may have a role in curing HIV through a method that is currently under investigation. This method calls for reactivating CD4⁺ cells and targeting cells expressing HIV antigen.

Activated cells produce virions that spread elsewhere in the body, thereby undermining curative efforts without a medication such as a small ubiquitin-like modifier protease inhibitor.