Stribild, a medication to treat HIV-1 infection for treatment-naïve adults, has been approved by the Food and Drug Administration (FDA). Stribild is a pill combination of four active ingredients – elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg – and is taken once a day. Treatment-naïve patients means those who have never been treated for HIV infection before.
What is the difference between HIV-1 and HIV-2 infection? – there are two types of HIV: HIV-1 and HIV-2. They are both transmitted through blood, by sexual contact, or from mother-to-child, and when they cause AIDS, the symptoms are indistinguishable. HIV-2 is less easily transmitted. Globally, most HIV infections are of HIV-1. HIV-2 is located in West Africa and hardly ever seen elsewhere. When referring to HIV without specifying, people are nearly always referring to HIV-1.
Elvitegravir, an HIV integrase strand transfer inhibitor, was discovered by Japan Tobacco and licenced to Gilead Sciences. The medication interferes with an enzyme that HIV needs to multiply. This is the first time anything created by Japan Tobacco has been approved by the FDA.
Emtricitabine, tenofovir disoproxil fumarate had already been FDA approved for HIV treatment; elvitegravir and cobicistat are new approvals.
Cobicistat inhibits an enzyme that breaks down some HIV medications – it prolongs elvitegravir’s effect – is a pharmacokinetic enhancer or pharmacoenhancing agent.
The emtricitabine and tenofovir disoproxil fumarate combination was approved in 2004 and had the brand name Truvada – it blocks another enzyme’s action which helps HIV replication in the human body. In combination, these medications provide a comprehensive treatment regimen for HIV infected patients.
Edward Cox, M.D., M.P.H., director of the Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research, said:
“Through continued research and drug development, treatment for those infected with HIV has evolved from multi-pill regimens to single-pill regimens. New combination HIV drugs like Stribild help simplify treatment regimens.”
Gilead says it is seeking approval for elvitegravir as a stand-alone medication.
FDA scientists evaluated two double-blind clinical trials which tested the safety and efficacy of Stribild, involving 1,408 HIV infected adults who had never been treated before. The participants were randomly selected into different groups, one was given Stribild and the other Trivada + atazanavir and ritonavir once daily in the second study.
The main aim of the trials was to see what percentage of participants had no measurable amounts of HIV in their blood at the end of 48 weeks.
The trials showed that at the end of 48 weeks:
- 88% and 90% of those in the Stribild groups had undetectable HIV amounts in their blood
- 84% of the Atripla and 87% of the Truvada + atazanavir and ritonavir groups had undetectable amounts of HIV
Principal investigator of one of the Stribild pivotal studies, Paul Sax, MD, Clinical Director of the Division of Infectious Diseases at Brigham and Women’s Hospital, Boston, and Professor of Medicine at Harvard Medical School, said:
“Over the past decade, co-formulated HIV medicines have simplified therapy for many patients and have become standard of care. Today’s approval of Stribild will provide physicians and their patients an effective new single tablet treatment option for individuals starting HIV therapy for the first time.”
This is the third single tablet HIV medication Gilead has developed. Atripla, the first, was approved in the USA in 2006, the second Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) was approved in 2011. Complera is a combination of Truvada, a Gilead drug, and rilpivirine, a Janssen medication.
Gilead says marketing approvals for Stribild are still pending in several major markets, including the European Union, Canada and Australia. Several Indian manufacturing partners have been granted permission to manufacture generic versions of Stibild for over 100 developing nations.
Stribild’s label has a Boxed Warning regarding an accumulation of lactic acid in the blood (lactic acidosis), as well as severe liver complications (hepatomegaly with steatosis). Doctors and patients are warned that both complications can be life-threatening. The label adds that Stribild is not approved for the treatment of chronic hepatitis B virus infection.
The following side effects are possible for patients taking Stribild – diarrhea, nausea, worsening kidney problems, immune reconstitution syndrome, decreased bone mineral density, and fat redistribution.
Giliead Sciences has to carry out further studies to evaluate Stribild’s safety in children and women, as well as potential interactions with other medications. The FDA also requires that Gilead organizes studies to see how resistance to Stribild develops.
Written by Christian Nordqvist