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 have been applied to other retroviruses. The class of integrase inhibitors called integrase strand transfer inhibitors are in established medical use. Other classes, such as integrase binding inhibitors, are still experimental. The development of integrase inhibitors led to a first approval for the class by the U.S. Food and Drug Administration on October 12, 2007, for raltegravir. Research published at the time supported the conclusion 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.
Raltegravir, brand name Isentress, developed by Merck & Co., was the first INSTI approved by the FDA on October 2007. Two formulations of raltegravir are currently available: 400 mg tablets and 600 mg tablets.
On August 27, 2012, following a successful Phase 3 clinical trial, Elvitegravir, licensed by Gilead Sciencesfrom Japan Tobacco, was approved by the U.S. Food and Drug Administration for use in adult patients starting HIV treatmentfor the first time as part of the fixed dose combination with emtricitabine and tenofovir disoproxil. Elvitegravir is a low-molecular-weight, highly selective integrase inhibitor that shares a core structure with quinolone antibiotics. A similar fixed dose combination containing tenofovir alafenamide instead of tenofovir disoproxil is offered under the brand name Genvoya. In every case, elvitegravir is given together with the "booster" cobicistat. Boostering of elvitegravir with cobicistat is similar to that of protease inhibitors by ritonavir.
Dolutegravir, brand name Tivicay, licensed by ViiV Healthcare, was approved by the FDA in 2013 and has recently gained European approval in January 2014. Dolutegravir is marketed as 50 mg tablets as a once or twice daily in a combination ART therapy together with two NRTIs. One dose daily is often sufficient, though in cases of viral resistance, a twice dose daily regimen—taken together with food, to further increase bioavailability—is recommended. A fixed combination therapy of dolutegravir with the NRTIs abacavir and lamivudine is available under the brand name Triumeq, a one-pill, once-daily complete ART regimen.
