Raltegravir-based regimen may be effective in treatment-naive patients

Raltegravir performed well in head-to-head comparison with efavirenz.

Issue: December 2008

WASHINGTON — HIV RNA levels were reduced to less than 50 copies/mL in 86% of treatment-naive patients who were treated with raltegravir, according to results of a new study.

The study results were presented at the 2008 ICAAC/IDSA Meeting by Jeffrey Lennox, MD, professor of medicine at Emory University School of Medicine in Atlanta. An international group of researchers enrolled 563 patients in the STARTMRK trial. There were 281 patients in the raltegravir (Isentress, Merck) arm and 282 patients in the efavirenz (Sustiva, Bristol-Myers Squibb) arm. Eligible patients had a baseline viral load of more than 5,000 copies/mL and were required to be screened for non-nucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor resistance. Patients were randomly assigned in a 1:1 ratio to receive therapy with either 400 mg twice-daily raltegravir or placebo or 600 mg once-daily efavirenz or placebo. Both treatment groups also received fixed-dose emtricitabine/tenofovir (Truvada, Gilead).

Results from 48 weeks were presented, but the trial is ongoing. The primary endpoint was suppression of HIV RNA levels to less than 50 copies/mL. The noninferiority margin was 12%.

Eighty-six percent of patients in the raltegravir arm had HIV RNA levels less than 50 copies/mL compared with 82% of patients in the efavirenz arm at the 48-week mark.

There was an 8.5% discontinuation rate in the raltegravir group and a 12.4% discontinuation rate in the efavirenz group.

Results also showed that raltegravir performed statistically better than efavirenz with regard to tolerability.

Positive outlook

Paul Volberding, MD, professor and vice chair of the University of California at San Francisco department of medicine and a member of the Infectious Disease News editorial advisory board, said the results of this study are promising. “The field is ready for this. HIV treatment research is a field where there have been real benchmark studies and benchmark drugs,” Volberding said. “Efavirenz has been that benchmark since 1998 or so. It has been a longstanding drug that has been incredibly helpful, but in raltegravir we have a drug that may stand up against it in treatment. It will be interesting to see how the results play out.”

Volberding discussed the mechanism of action of raltegravir, an integrase inhibitor, and said that it can work against a virus that is resistant to other drugs. Also, raltegravir appears to be more potent in suppressing the virus and may act more rapidly than efavirenz. He said that it may be a natural step for raltegravir to move from its current approval status as a salvage therapy drug to a first-line therapy for treatment-naive patients. “This does not mean that raltegravir should be preferred initial therapy, but it puts it up there for continued serious discussion,” he said.

Further, researchers are gathering data in support of raltegravir as a once-daily treatment. “Evidence demonstrating extended cellular activity of raltegravir is mounting. This may make it a likely candidate for once-daily dosing,” Volberding said. “The future looks bright for raltegravir, and the future looks bright for HIV therapy.” – by Rob Volansky

For more information:

Lennox J. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive HIV-1 infected patients: STARTMRK protocol. Presented at: the 2008 ICAAC/IDSA Meeting; Oct. 25-28,