Integrase Inhibitor

Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment of HIV infection, but they could be applied to other retroviruses. The first integrase inhibitor approved by the U.S. Food and Drug Administration (FDA) was Raltegravir (brand name Isentress), approved on October 12, 2007. Research results published in the New England Journal of Medicine on July 24, 2008, concluded that "raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks." Since integrase inhibitors target a distinct step in the retroviral life cycle, they may be taken in combination with other types of HIV drugs to minimize adaptation by the virus. They are also useful in salvage therapy for patients whose virus has mutated and acquired resistance to other drugs. What are Integrase Inhibitors? In order for HIV to successfully take over a CD4 cell's machinery so that it can produce new viruses, HIV's RNA is converted into DNA by the reverse transcriptase enzyme (nucleotide/nucleoside reverse transcriptase inhibitors can block this process). After the "reverse transcription" of RNA into DNA is complete, HIV's DNA must then be incorporated into the CD4 cell's DNA. This is known as integration. As their name implies, integrase inhibitors work by blocking this process. Integrase inhibitors may offer a lot of hope for HIV-positive people, especially those who have developed HIV resistance to drugs that target HIV's two other major enzymes: reverse transcriptase and protease. Merck's Isentress (raltegravir) was approved by the U.S. Food and Drug Administration (FDA) in October 2007. Gilead's elvitegravir (GS-9137) is in advanced clinical trials and a third compound, ViiV Healthcare's GSK-572, is in Phase II studies.