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Dolutegravir Superior to Efavirenz in a Head-to-Head Study

Summary and Comment |
November 7, 2013

Dolutegravir Superior to Efavirenz in a Head-to-Head Study

  1. Paul E. Sax, MD

Both regimens were highly efficacious virologically, but the dolutegravir-based therapy was better tolerated.

  1. Paul E. Sax, MD

Dolutegravir is a potent, once-daily integrase inhibitor that was approved by the FDA earlier this year based on the results of three phase III clinical trials. In one of these trials (SINGLE), sponsored by the makers of dolutegravir, an abacavir/3TC plus dolutegravir regimen was compared with coformulated tenofovir/FTC/efavirenz.

The study was conducted in North America, Europe, and Australia; 844 treatment-naive, HLA*B5701-negative patients were randomized to receive the dolutegravir- or efavirenz-based regimen, along with matching placebos. The study population was well matched (overall, 84% men, 24% black; median viral load, 4.68 log copies/mL; median CD4 count, 338 cells/mm3).

At week 48, 88% of the dolutegravir group and 81% of the efavirenz group had viral loads <50 copies/mL using an FDA “snapshot” analysis; this 7% difference not only met the study's noninferiority threshold, but also allowed the investigators to conclude that the dolutegravir regimen was superior (P=0.003). Virologic failures were comparably rare in both arms, but 10% of the efavirenz group and 2% of the dolutegravir group discontinued the study drug because of adverse events. No resistance to either dolutegravir or the nucleoside reverse transcriptase inhibitors was detected in patients experiencing virologic failure on dolutegravir; five patients on tenofovir/FTC/efavirenz developed resistance.

Comment

This prospective clinical trial is the first in which an efavirenz-based initial regimen has been bested by a comparator. Although both regimens were highly efficacious virologically, the dolutegravir regimen was better tolerated, with fewer treatment discontinuations. An additional benefit was the lower incidence of resistance with dolutegravir than with efavirenz among patients with treatment failure. A coformulated single tablet of abacavir/3TC/dolutegravir is currently in development. Based on the results of this trial and the other phase III studies of this drug — SPRING-2 (NEJM JW AIDS Clin Care Feb 11 2013) and FLAMINGO — the recently updated Department of Health and Human Services Guidelines list both tenofovir/FTC plus dolutegravir and abacavir/3TC plus dolutegravir as preferred options for initial therapy (NEJM JW AIDS Clin Care Nov 4 2013).

  • Disclosures for Paul E. Sax, MD at time of publication Consultant / Advisory board Bristol-Myers Squibb; Gilead; GlaxoSmithKline; Janssen; Merck Grant / research support NIH; Bristol-Myers Squibb; Gilead; GlaxoSmithKline; Merck Editorial boards Medscape; UpToDate Leadership positions in professional societies Mass ID Society (Vice President)

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