Fusion inhibitors are a new class of drugs offered to patients with HIV-1 strains resistant to standard drug treatment. The U.S. Food and Drug Administration (FDA) approved Trimeris and Hoffmann-La Roche’s Fuzeon (enfuvirtide) in March 2003 and Pfizer’s Selzentry (maraviroc) in August 2007 to accompany current antiviral regimens.

Fuzeon is injected into the body, while Selzentry is taken orally. Both drugs work by preventing the virus from entering and infecting human immune cells. Fuzeon binds to an HIV protein and blocks its necessary conformational change to bring the viral and cellular membranes together. Selzentry prevents the virus from binding to a host cell protein that HIV uses as a co-receptor to preferentially infect macrophages. This binding is necessary to form a stable interaction between the two membranes.

In addition to providing drug-resistant HIV patients with a new treatment alternative, Fuzeon and Selzentry have been proven effective in clinical trials. Results published in July of 2007 showed 64 percent of participants taking Fuzeon achieved undetectable levels of HIV, which is less than 50 copies of the virus per mL of blood. Selzentry clinical trial results in February earlier that year showed significant increases in HIV suppression and CD4 T cell counts in comparison to control groups.

Drawbacks to fusion inhibitors include their administration, side effects, and restricted application. Fuzeon requires injection twice a day and causes injection site reactions. During clinical trials, participants taking Fuzeon had increased incidences of bacterial pneumonia. Selzentry is broken down by the liver and may cause complications with other medications. Its usage is limited by the type of HIV virus and will be much less effective against strains that use a different co-receptor. Additionally, both of these drugs are not recommended for people undergoing therapy for the first time.

Other experimental drugs are still awaiting FDA approval. Schering-Plough’s Vicriviroc, Progenics’s PRO140, and Tanox’s TNX-355 all inhibit different proteins involved in HIV attachment and fusion, which is necessary for the virus to infect healthy human cells and cause the disease.