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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 Journal Watch. Journal Watch is a publication of the Massachusetts Medical Society.
 

Reader Comments:

Comment by: leslie m. (nashville tn) Mon., Sep. 10, 2012 at 4:27 pm EDT
The pronounciation is long "i" in the first syllable, and a short "i" in the second. Agree it doesn't roll off the tongue easily and wonder how it was conceived!
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Comment by: michael (los angeles) Sun., Sep. 2, 2012 at 8:22 am EDT
no thoughts on the cost? no doubt it will most likely be double the price of atripla, even though already warned by the govt to be careful of pricing it.....fearing that these "angels" who produce the quad might price it in the 32k/year range.......

ridiculous......
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Replies to this comment:
Comment by: John V. (Clarksville, TN) Thu., Sep. 6, 2012 at 1:27 pm EDT
Michael, cost was addressed in this article:

"...and in the future to pharmacoeconomic factors, as generic antiretroviral strategies will become increasingly available that might challenge use of coformulated regimens."

Quad (Stribild) is abusively costly, especially considering all components belong to Gilead.

Gilead is an innovator, or was at one time, and is simply striking while irons remain hot. After all, Gilead is an investor owned enterprise.

I am very much a capitalist, but there is a point where pricing becomes arbitrary. Arbitrarily stratospheric pricing, in excess of millions of middle class salaries, is simply working the system over with a metal pole before taking its wallet.

We can be thankful for Gilead's innovation, and no one is thankless here. However, we can be equally critical of Gilead's insult and injury to the HIV community, both of which are now in greater supply than their innovation.

Antiretrovirals have, with appreciation to all involved, become a mature market. Is Quad/Stribild such a fascinating pharmacological adventure as to warrant a $30,000 annual price? Is Atripla so much more advanced than in 2006 to warrant being sold for $7,000 more annually now?

The answer to both questions is no, and Gilead is adding as much blood to their hands as quantities of life saved.

Gilead knows HIV is, while currently not cured, on the run for a timely breakthrough comfortably within a decade (or two, perhaps). No man knows the hour HIV will be cured, or if it will in our lifetimes.

We do know generic options will be arriving within a few years which will provide more affordable options for giant swaths of people. Gilead will experience a tiny sting of undoing with each treatment-naive who chooses a multi-pill strategy at an 80% discount.

Until then, Gilead will keep a gun firmly to the heads of those with a gun already inside them.

Gilead is walking irony, a medical tragedy borne of uniquely American success.


Comment by: Gustavo P. (Belo Horizonte, Minas Gerais, Brasil) Thu., Aug. 30, 2012 at 2:55 pm EDT
Very hopeful news. I have been discussing with my doctor about the side-effects of the current treatments, and she said to me that the current drugs are part of a pool of drugs launched due to the urgency to treat the HIV infection effectively, but there wasn´t much knowledge yet about the side-effects. So now, it seems that it´s becoming easier to deal with that, based on practical data from the current users of ARTs.
I still didn´t started my treatment because my virus load and CD4 are under control yet. But I feel afraid, specially because of side-effetcs. So, that kind of news bring me, and I think for more people like me, some hope, so we can take an almost normal life after treatment starts.
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Comment by: ZacWolf (Durham, NC) Thu., Aug. 30, 2012 at 1:46 pm EDT
Is there any data comparing side-effects profile of this vs. a regimen of once-a-day Truvada, paired with twice-a-day Isentress?
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