Fusion inhibitors

After HIV’s gp120 envelope glycoprotein attaches to a CD4 receptor and a co-receptor on the cell, a different glycoprotein, called gp41 , is exposed. The glycoproteins then undergo shape changes that bring the virus and the cell closer together, allowing them to fuse.

There is a single licensed fusion inhibitor:

• T-20 (enfuvirtide, Fuzeon).

T-20, developed by Roche and Trimeris, binds to the gp41 glycoprotein and prevents the shape changes that enable virus-cell fusion. Since T-20 is a protein that would be destroyed by acids in the stomach, it must be administered by injection.

The TORO 1 and TORO 2 studies showed that adding T-20 to an existing antiretroviral regimen can improve response in treatment-experienced patients with drug-resistant HIV.^{1 2} Thus, it is often used as a component of ‘salvage therapy’.

A successor to T-20, known as T-1249, was discontinued due to difficulties with its formulation. However, researchers are working on new fusion inhibitor candidates in the hopes of developing either an oral drug or one that can be injected less often. Two such candidates, TRI-1144 and TRI-999, demonstrated good pharmacokinetics and antiviral potency in laboratory studies and appear to have a higher barrier to resistance than T-20.^{3 4}

For more information on this drug, see A to Z of antiretroviral drugs.