Brand name: Not yet established
Generic name: elvitegravir/cobicistat/emtricitabine/tenofovir, or EVG/COBI/FTC/TDF
Class: Boosted integrase inhibitor and NRTI -- single-tablet regimen (STR)
Manufacturer: Gilead Sciences, www.gilead.com, (800) GILEAD-5 (445-3235)
AWP: TBD; drug not yet approved at press time.
Standard Dose: One tablet (150 mg elvitegravir/150 mg cobicistat/200 mg emtricitabine/300 mg tenofovir ) once daily has been selected in the Phase 3 studies. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. Dose cannot be adjusted for people with kidney problems.
Potential side effects and toxicity: See the individual drugs contained in the Quad: elvitegravir, Emtriva, Viread, and cobicistat. Seen in clinical study: Fatigue, diarrhea, headache, nausea, abdominal distention, rash, elevated lipid levels (cholesterol and triglycerides), increased serum creatinine, and decreased estimated glomerular filtration rate (e-GFR) -- the last two are signs of possible kidney malfunction (see cobicistat page for more, and reassuring, information). Available data are limited due to investigational drug status. See chart for potential drug class side effects.
Potential drug interactions: Do not take this drug with Atripla, cobicistat, Combivir, Complera, elvitegravir, Emtriva, Epivir, Epivir-HBV, Epzicom, Trizivir, Truvada, or Viread, since these medications are already in this fixed dose pill or it has equivalent medications. Because the Quad has cobicistat in it and cobicistat is a potent CYP3A4 inhibitor, there are expected to be numerous drug interactions. A complete list will be available in the package insert once the Quad is FDA approved. Again, available data are limited due to its investigational drug status.
More information: Still in experimental study, Gilead's New Drug Application for the Quad was accepted by the FDA on December 23, 2011 and it has set a target review date of August 27, 2012. If approved, the Quad would be the third (see Atripla and Complera) once-daily, single-tablet HIV regimen and the only one containing an integrase inhibitor (INSTI). Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Isentress is the only INSTI currently on the market. In 2011, 48-week data showed the Quad was non-inferior (no better, no worse), as shown by achieving undetectable viral load of less than 50 copies per mL, to Atripla (Study 102, 88% for the Quad vs. 84% for Atripla) and to Norvir-boosted Reyataz with Truvada (Study 103, 90% for the Quad vs. 87% for boosted Reyataz). Complete Quad data are expected to be presented this year at a scientific conference. Elvitegravir must be taken with a booster medication to raise its blood levels; in the Quad, the booster is cobicistat. The Quad pill will be smaller in size than Atripla. See package insert, when available, for more complete information on potential side effects and drug interactions.
The so-called "Quad" is expected to be approved later this year, which will make it the third approved single-tablet regimen. In recent clinical trials, it was well tolerated and as effective as Atripla or the combination of Truvada plus Reyataz/Norvir for initial therapy. Interestingly, the Quad will be approved before its novel component drugs, elvitegravir and cobicistat. It's important to monitor kidney function when taking the Quad. As we know, the tenofovir component can sometimes cause kidney toxicity, and cobicistat, while not toxic to kidneys, does decrease creatinine secretion. This causes a small rise in the serum creatinine, which can give the appearance of kidney toxicity.
-- Joel Gallant, M.D., M.P.H.
Okay, I'm all for single-tablet regimens (STRs), they help most folks stay on track and avoid missing doses. We were all hoping this was going to be The One. Now we hear the booster is no better than the existing one, and there are some unsettling side effects from the other drugs. I guess it's not going to be the blockbuster we were hoping to have (sigh). I'm sure it will do wonders for some, but if you have kidney problems, this one may be a pass for you.
-- Joey Wynn