What are Attachment and Entry Inhibitors?
Entry inhibitors work by preventing HIV from entering healthy CD4 cells (T-cells) in the body. They work differently than many of the approved anti-HIV drugs—the protease inhibitors (PIs), the nucleoside reverse transcriptase inhibitors (NRTIs), and the non-nucleoside reverse transcriptase inhibitors (NNRTIs)—which are active against HIV after it has infected a CD4 cell.
Entry inhibitors work by attaching themselves to proteins on the surface of CD4 cells or proteins on the surface of HIV. In order for HIV to bind to CD4 cells, the proteins on HIV's outer coat must bind to the proteins on the surface of CD4 cells. Entry inhibitors prevent this from happening. Some entry inhibitors target the gp120 or gp41 proteins on HIV's surface. Some entry inhibitors target the CD4 protein or the CCR5 or CXCR4 receptors on a CD4 cell's surface. If entry inhibitors are successful in blocking these proteins, HIV is unable to bind to the surface of CD4 cells and gain entry into the cells.
Two entry inhibitors have been approved by the the U.S. Food and Drug Administration (FDA). Roche's Fuzeon (enfuvirtide), approved in March 2003, targets the gp41 protein on HIV's surface. Pfizer's Selzentry (maraviroc), approved in August 2007, targets the CCR5 protein. Experimental drugs include Tobira Therapeutics' cenicriviroc, Progenics's CCR5-blocking monoclonal antibody PRO 140, and Tanox's TNX-355, a drug that targets the CD4 protein on CD4 cells.
HIV-positive people who have become resistant to PIs, NRTIs, and NNRTIs will likely benefit from the entry inhibitors because they are a different class of drugs. This is good news for HIV-positive people who have tried and failed many of the currently approved anti-HIV medications.
To learn more on how HIV infects a CD4 cell and begins to create more viruses, and where each class of anti-HIV drugs blocks this process, click on the following lesson link:
The HIV Life Cycle (and the targets of each class of anti-HIV drugs)