The Next Frontier in the Management of HIV/AIDS

The introduction of fusion inhibitors heralds a major milestone in the management of HIV. The first compounds in an entirely new treatment class to reach clinical testing, fusion inhibitors attack HIV at a recently identified viral stage – HIV’s fusion to the human immune cell. Fusion is an early stage in the viral life cycle in which the virus penetrates the protective membrane of a human CD4 cell, the immune cell targeted by HIV. Once HIV enters the cell, it commandeers the cell’s machinery to make more virus.

By preventing HIV from binding to and entering CD4 cells, fusion inhibitors make it possible to stop the process of viral replication before it starts.

Until now, there have been two main avenues of attacking HIV with antiviral drugs -- reverse transcriptase inhibitors (nucleoside, non-nucleoside, or nucleotide) and protease inhibitors. These drugs all interfere with various stages of HIV’s replication process. Combinations of these agents have yielded significant results in reducing HIV viral load and boosting CD4 counts, dramatically slowing disease progression and prolonging survival in millions of people.

While these drugs have provided significant benefits to millions, HIV can develop resistance over time; in addition, some have side effects that make them difficult for patients to take for extended periods of time. Driving the critical need for therapies that attack HIV at another point of entry, these agents typically engender resistance over time, making them less and less able to ward off the disease.

The World’s First Fusion Inhibitors: T-20 and T-1249

Two novel anti-HIV fusion inhibitors, T-20 and newer-generation T-1249, are currently in clinical trials. Preliminary data show that both compounds produce potent, durable anti-HIV effect, even in people who have had extensive previous exposure to existing HIV medications. Both compounds block the HIV receptors that link the virus to the CD4 cell and trigger the process by which HIV enters the cell.

In addition, unlike the recently introduced reverse transcriptase inhibitors or protease inhibitors, T-20 is not cross-resistant to any of the currently available agents. Because its mechanism of action works outside the cell membrane, this may contribute to the compound’s low side-effect profile.