One of the critical steps in the HIV life cycle is the integration of the virus's genetic information into the host cell DNA. This allows the host cell to turn into a "HIV factory" and produce many, many virions each hour. The enzyme integrase is the enzyme that accomplishes this task. Integrase inhibitors serve to stop this enzyme.
Integrase inhibitors are oligonucleotides, which are small segments of DNA or RNA that are synthetically prepared. Modified oligonucleotides can serve to block RNA/DNA interactions and modify protein or enzyme synthesis.
One drawback to integrase inhibitors is that it only has one chance to act for each cell. If it fails, any further attempts are futile since the genetic information is already incorporated. In contrast, NRTI's have thousands of opportunities to act during the process of reverse transcription.
Merck has developed an experimental integrase inhibitor called L-870,812. The drug was tested on six HIV positive monkeys. At the end of 75 days, four of the monkeys reached undetectable levels of HIV. The other two monkeys didn't receive the same amount of the drug, but still showed improvement over the control group.
Currently, there are no integrase inhibitors available on the market. Dr. Sally Hodder, Vice President of Bristol-Myers Squibb Virology, predicts that if the development of integrase inhibitors result in marketed products, these drugs may become popular in the next 5 to 10 years.
Sources:
- Hodder, Sally. Personal interview. 23 Jan. 2004.
- Oligonucleotides . 18 July 2000. 21 Feb. 2004 <http://www.hivpositive.com/f-Treatment/5-Treatments/f-Integrase/oligos.html>.
- "Third and Final Enzymatic Target." . Apr. 1995. Treatment Action Group. 21 Feb. 2004 <http://www.thebody.com/tag/tagapr2.html>.
- Kresge, Kristen. "Integrase Inhibitors Update." Treatment Insider . 2004. American Foundation for AIDS Research. 21 Feb. 2004 <http://www.amfar.org/cgi-bin/iowa/td/newsan/record.html?record=72>.