FDA Approves 2 HIV-1 Cocktail Drugs

September 25, 2014

The US Food and Drug Administration (FDA) has approved 2 new HIV-1 cocktail drugs from Gilead Sciences, one an integrase inhibitor called elvitegravir (Vitekta) and the other a protease-inhibitor booster called cobicistat (Tybost), the agency announced today.

Both drugs received market clearance last year from the Committee for Medicinal Products for Human Use of the European Medicines Agency.

As an integrase inhibitor, elvitegravir prevents HIV-1 from inserting its DNA into the DNA of the cells it has infected. The FDA approved it for patients with HIV-1 who have previously received antiretroviral treatment. Rather than acting as a stand-alone drug, elvitegravir is indicated in combination with an HIV protease inhibitor coadministered with ritonavir (a booster) and another antiretroviral. It must be taken once a day with the other drugs, along with food. It comes in 85- and 150-mg tablets.

The FDA based its approval on a phase 3 clinical trial in which 712 adults with HIV-1 and a history of antiretroviral treatment received either elvitegravir once daily or a 400-mg dose of raltegravir twice daily in combination with a fully active protease inhibitor, ritonavir, and another antiretroviral drug for at least 96 weeks.

"Virologic outcomes were similar across the treatment arms through 96 weeks," the agency stated in a news release.

Diarrhea (7%), nausea (4%), and headache (3%) were the most common adverse event for patients receiving elvitegravir. The rates of these adverse events were comparable with those for raltegravir.

The FDA does not recommend elvitegravir for patients with severe hepatic impairment because it has not been studied in this population.

Cobicistat Approval

Cobicistat is indicated in a 150-mg dose for patients with HIV-1 to increase blood levels of the protease inhibitors atazanavir or darunavir in a once-a-day regimen.

In a clinical trial, the combination of a 150-mg dose of cobicistat, a 300-mg dose of atazanavir, and emtricitabine/tenofovir (Truvada, Gilead Sciences) in treatment-naive adults proved noninferior to ritonavir and the other 2 drugs. A multiple-dose trial in healthy patients comparing a 150-mg dose of cobicistat and an 800-mg dose of darunavir with a 100-mg dose of ritonavir and darunavir justified the use of cobicistat as a booster, according to the FDA.

Jaundice, ocular icterus, and nausea were the most common adverse events observed in combination with atazanavir.

There is a long list of drugs contraindicated for patients taking cobicistat and either atazanavir or darunavir, including dronedarone, rifampin, cisapride, and triazolam.

How Much Effect?

The 2 newly approved HIV-2 drugs "are unlikely to have a major effect on clinical practice," said Paul Sax, MD, a professor of medicine at Harvard Medical School and clinical director of the Infectious Diseases Division at Brigham and Women's Hospital in Boston, Massachusetts.

"Elvitegravir...already comes coformulated with 3 other drugs as part of a complete regimen given as 1 pill," Dr. Sax said to Medscape Medical News. "As a separate entity, it does not have clear benefits over either raltegravir or dolutegravir.

"Additionally, coformulated versions of cobicistat with both darunavir and atazanavir are expected to be approved by the FDA soon; they will be more convenient than giving the drugs separately."


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