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July 14th, 2013
Will Dolutegravir Instantly Become the Integrase Inhibitor of Choice in Patients with Treatment Failure?
And here’s why.
In a randomized, double blind clinical trial just published in the Lancet — it’s called SAILING — once-daily dolutegravir was compared to twice daily raltegravir in treatment-experienced patients. The site investigators could choose one or two other fully active agents to develop an optimized background regimen (OBR). There was a protocol-specified stratification based on fully-active darunavir and baseline viral load.
There were over 700 study subjects; they were recruited from 156 sites, located in every continent except Antarctica.
(Yes, 156 sites. Hey, it’s hard to find patients who fail treatment who are good candidates for clinical trials!)
And here are the results:
- Virologic outcome: Dolutegravir was superior to raltegravir, 71% suppressed at 48 weeks, vs 64%, p=0.03.
- Those experiencing virologic failure had less resistance on dolutegravir than raltegravir.
- In the hardest-to-treat subgroups — those with no active darunavir in their OBR, or the higher viral load stratum — the differences favoring dolutegravir over raltegravir were even greater than in study overall.
- Adverse events, serious or otherwise — pretty much the same.
Now I’ve said before that raltegravir is one of our very best antiretroviral agents: it’s highly potent, well tolerated, has very few drug-drug interactions, an extensive safety record dating back to clinical trials that started in the mid-2000s, and and even more extensive favorable clinical experience since its approval in 2007.
But dolutegravir is once daily, seems just as well tolerated as raltegravir, has a similar drug-drug interaction profile — and based in the results of SAILING, is probably more potent and less prone to resistance.
Note that elvitegravir isn’t currently in the discussion, since it’s not available except as part of this one pill — TDF/FTC/EVG/COBI — which can’t be given with boosted PIs, so is a difficult choice in those with treatment failure.
Bottom line: barring some unexpected toxicity when it gets into broader use after approval — always a possibility — dolutegravir will instantly become the integrase inhibitor (II, INI, INSTI, InSTI) of choice in treatment experienced patients with treatment failure.
(Still need a good abbreviation for this drug class.)