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 HIVs 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 cells
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 HIVs
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 Worlds 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 compounds low side-effect profile.
It is anticipated that fusion inhibitors in combination with protease inhibitors and/or
reverse transcriptase inhibitors may provide more effective suppression of HIV and protect
against disease progression.