Clinical Context

Persons with HIV-1 infection benefit more from individually tailored treatment regimens than from a "one-size-fits-all" approach. Approval of new antiretroviral drugs such as dolutegravir increases the range of available options in the treatment armamentarium.

In February 2013, the US Food and Drug Administration (FDA) granted dolutegravir priority review status. On August 12, it was approved, only 4 days after approval of the first rapid diagnostic test for HIV types 1 and 2 antibodies and for the HIV-1 p24 antigen.

Study Synopsis and Perspective

On August 12, The FDA approved a new drug called dolutegravir (Tivicay) as an adjunct to other antiretroviral drugs that treat individuals infected with HIV-1, the agency announced.

Dolutegravir, an integrase strand transfer inhibitor, interferes with an enzyme needed for HIV to multiply. It is a once-a-day pill.

The new drug is indicated for HIV-infected adults who have never taken HIV antiretroviral therapy as well as for HIV-infected adults who have previously received this therapy, including other integrase strand transfer inhibitors. Clinicians also can order dolutegravir together with other antiretrovirals for children aged 12 years or older, weighing at least 40 kg, who are treatment naive or treatment experienced but have not previously received other integrase strand transfer inhibitors, a restriction not found with adults.

"HIV-infected individuals require treatment regimens personalized to fit their condition and their needs," said Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research. "The approval of new drugs like Tivicay that add to the existing options remains a priority for the FDA."

In February, the agency granted priority review status to dolutegravir. Its approval comes 4 days after the FDA okayed the first rapid diagnostic test to spot antibodies to both HIV types 1 and 2 as well as the HIV-1 p24 antigen.

The FDA determined that dolutegravir is safe and effective on the basis of 4 clinical trials involving 2539 participants with HIV. Drug regimens for treating HIV that included dolutegravir proved effective in reducing viral loads, according to the agency. The pharmacokinetics, safety, and activity of the drug with regard to children defined in the pediatric indication were established in a fifth clinical trial.

Insomnia and headache were common adverse events observed in the clinical trials. Among the more serious adverse events were hypersensitivity reactions and abnormal liver functions among patients who also were infected with hepatitis B or C, or both. The drug's label contains instructions on how to monitor patients for such serious adverse events.

More information on the FDA decision is available on the agency Web site.

Clinical Implications

• The FDA has approved dolutegravir, an integrase strand transfer inhibitor, to treat HIV-1 infection when used as an adjunct to other antiretroviral drugs. This once-daily pill formulation is indicated for treatment-naive HIV-infected adults as well as for HIV-infected adults previously treated with integrase strand transfer inhibitors and/or other antiretroviral therapy. Children at least 12 years old and weighing at least 40 kg may receive dolutegravir along with other antiretroviral therapy if they are treatment naive or treatment experienced, but not if they previously received other integrase strand transfer inhibitors.
• Evidence from 4 clinical trials suggests that dolutegravir is safe and effective in reducing viral loads when used in drug regimens for treating HIV. A fifth clinical trial demonstrated the pharmacokinetics, safety, and activity of dolutegravir in children.
• Adverse events reported in clinical trials of dolutegravir used for HIV-1 infection included common adverse events of insomnia and headache. More serious adverse events included hypersensitivity reactions and abnormal liver functions in patients coinfected with hepatitis B and/or hepatitis C. The label for dolutegravir includes information regarding monitoring of patients for serious adverse events.

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