Thoughts on "Quad" Approval by FDA

August 28, 2012

Paul E. Sax, M.D.

Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.

We now have a third single-pill treatment available for HIV treatment, co-formulated tenofovir/emtricitabine/elvitegravir/cobicistat. From the FDA announcement:

The U.S. Food and Drug Administration today approved Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate), a new once-a-day combination pill to treat HIV-1 infection in adults who have never been treated for HIV infection. Stribild contains two previously approved HIV drugs plus two new drugs, elvitegravir and cobicistat ... Together, these drugs provide a complete treatment regimen for HIV infection.

A few quick thoughts about this approval, with the disclosure that I was an investigator on one of the phase III studies that led to its approval:

  • The combination -- which I'll continue to call "Quad", at least for now -- is just as active virologically as two preferred initial regimens -- TDF/FTC/EFV (the first of the single pill treatments), and TDF/FTC + atazanavir/r (the most commonly used boosted PI regimen).
  • The side effect profile was different from TDF/FTC/EFV, with less CNS disturbance and rash, and more nausea; the side effects were quite similar to the boosted ATV/r regimen -- except for hyperbilirubinemia from atazanavir, of course -- possibly because cobicistat and ritonavir are related.
  • The renal issues with cobicistat are potentially tricky, as it causes a 0.1-0.2 mg/dL increase in creatinine that is related to inhibition of tubular secretion of creatinine, and hence does not actually decrease GFR. As a result, the regimen should not be used in patients with impaired renal function, and they were not studied in the Quad trials.
  • One potentially helpful number to remember is 0.4, as the small number of patients with tenofovir tubular toxicity in the Quad studies also had an increase in serum creatinine of at least this much -- hence distinguishing them from the more benign smaller increase from cobicistat.
  • Separate studies of Quad in patients with renal insufficiency and in women are planned (only a small proportion of study patients were women).

The bottom line is that Quad is an effective, very convenient option for initial HIV treatment. I suspect how much traction it gets from providers will depend on their experience in clinical practice related to safety and tolerability, and in the future to pharmacoeconomic factors, as generic antiretroviral strategies will become increasingly available that might challenge use of coformulated regimens.

(How about that name, "Stribild"? Pronounced with a long or short "I"? Wonder what the runner-ups were for that brand name.)

Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.

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This article was provided by NEJM Journal Watch. NEJM Journal Watch is a publication of the Massachusetts Medical Society.


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