Specifically, there are three steps of “entry” that HIV must accomplish: attachment, coreceptor binding, and fusion.
Attachment Inhibitors
The CD4 receptor is the primary receptor that HIV uses to bind to the cell and insert its genetic information. Experimental attachment inhibitors such as PRO 542 prevent HIV from ever attaching to the CD4 receptor.
Recent research has suggested that there are co-receptors other than CD4 that HIV must bind to in order to attach to the cell. One of the most prominent is the CCR5 co-receptor. There have been no uses for this receptor identified as of yet.
It has been found that people with the CCR5 gene missing or corrupted are generally resistant to the HIV virus. An experiment conducted on monkeys whose CCR5 receptors were inhibited resulted in the blocking of SHIV (Simian Human Immunodeficiency Virus), a similar strain to human HIV.
Current experimental drugs such as PRO 140 and TAK-779 are antibodies that block the interaction of HIV with the CCR5 coreceptor.
Even after HIV has attached to the cell, there are a complex series of reactions that occur to allow the viral genetic material to be injected into the cell. Fusion inhibitors serve to stop that.
T-20, or Fuzeon, is an experimental fusion inhibitor. It is a 36 amino acid synthetic peptide that corresponds to the protein gp41 on the surface of the HIV virion. (It is gp21 that allows the viral RNA to fuse with the cell.)
Future of Entry Inhibitors
At this time, there is one entry inhibitor on the market: Fuzeon (the brand name of T-20), which was approved in March 2003. Dr. Sally Hodder, Vice President of Bristol-Myers Squibb Virology, predicts that more entry inhibitors may become popular in the next five years.
For more information on the entry of HIV into the cell, please click here.
Sources:
- Boyle, Brian A. Potential Breakthroughs in Antiretroviral Therapy: The HIV Entry Inhibitors . 22 Sept. 2000. 10 Feb. 2004 <http://www.aidsmeds.com/news/v09220001.html>.
- "Co-Receptors - CCR5." Understanding HIV . Jan. 2003. Project Inform. 10 Feb. 2004 <http://www.projinf.org/fs/ccr5.html#fusin>.
- Grossman, Howard. Entry Inhibitors (including Fusion Inhibitors) . 06 Jan. 2003. 10 Feb. 2004 <http://www.aidsmeds.com/EIs.htm>.
- Hodder, Sally. Personal interview. 23 Jan. 2004.
- Pincock, Stephen. "CCR5 Inhibitor Is Effective HIV Microbicide in Monkeys." HIV/AIDS Top Stories . 16 July 2003. Reuters. 10 Feb. 2004 <http://www.hivandhepatitis.com/recent/experimental_drugs/071603j.html>.