Sometimes it takes three companies to take down a leader. Only time will tell whether that'll even be enough in the HIV space.

Shionogi set up a joint venture with ViiV to develop an HIV drug called dolutegravir. ViiV is itself an HIV-specialized joint venture between GlaxoSmithKline (NYSE: GSK) and Pfizer (NYSE: PFE).

In the first phase 3 trial, dolutegravir was deemed non-inferior to Merck's (NYSE: MRK) Isentress. Being just as good as Isentress is fine, since Merck's drug has to be taken twice daily while dolutegravir is taken only once a day. Isentress is a blockbuster, but it's not the top dog in the HIV space.

That spot clearly belongs to Atripla, which was developed by Gilead Sciences (Nasdaq: GILD) and Bristol-Myers Squibb (NYSE: BMY). If you're going to make headway in the HIV space, you have to at least match Atripla.

Dolutegravir did one better; it beat Atripla.

A three-drug combination containing dolutegravir and two older medications Kivexa and Epzicom trumped Atripla, a three-in-one drug. After 48 weeks of treatment, 88% of patients taking the dolutegravir-based regimen had reduced viral levels to the goal compared with 81% of patients taking Atripla. Given the large size of the trial, 414 patients in the dolutegravir arm and 419 in the Atripla arm, the difference was statistically significant.

Game over? Switch all the patents from Atripla to dolutegravir? Not so fast.

More patients taking Atripla dropped out of the study because of adverse events compared with those taking dolutegravir -- 10% versus just 2% -- which was the main driver of the difference in efficacy. Doctors aren't going to switch patients already on Atripla, because the medication is obviously working for them and they haven't had side effects that would cause them to discontinue.

The reduced side effects should give dolutegravir an advantage for new HIV patients going onto medication, which could slow Atripla's growth. But even there, being the entrenched leader has its perks. Doctors aren't going to change their habits overnight. They'll need to gain experience with dolutegravir -- once it's FDA-approved -- before turning it into their go-to HIV drug.

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