CROI: Integrase Inhibitor 'Striking' in Early Results

February 28, 2007

LOS ANGELES -- Raltegravir (MK-0518), an investigational anti-retroviral drug that targets the HIV enzyme integrase, seems highly effective in patients resistant to existing classes of drugs.

LOS ANGELES, Feb. 28 -- Raltegravir (MK-0518), an investigational antiretroviral drug that targets the HIV enzyme integrase, seems highly effective in patients resistant to existing classes of drugs.

In two international phase III trials, the drug significantly lowered HIV RNA levels and increased the number of immune cells in patients resistant to at least one drug in each of the approved classes of medications, according to David Cooper, M.D., of the University of New South Wales in Sydney, Australia.

Raltegravir blocks the integration of HIV DNA into the host cell genome, and is the first drug to target integrase, Dr. Cooper told the Conference on Retroviruses and Opportunistic Infections here.

The drug generated excitement when results from phase II trials were presented at the International AIDS Conference in Toronto last summer and later at the Interscience Conference on Anti-microbial Agents and Chemotherapy (ICAAC: Investigational Integrase Inhibitor Reduces HIV Load).

Dr. Cooper was principal investigator of the BENCHMRK-1 study, which enrolled 350 highly treatment-experienced patients in Europe and Australia and randomized them to an optimized background therapy plus either placebo or 400 milligrams of raltegravir twice daily.

A second study with the same design, BENCHMRK-2, enrolled 349 patients in North and South America, according to principal investigator Roy Steigbigel, M.D., of the State University of New York at Stony Brook.

Although the studies are intended to continue for several months, Drs. Cooper and Steigbigel presented data from the first 16 weeks. Nonetheless, Dr. Steigbigel characterized the results as "very striking."

Dr. Cooper said the BENCHMRK-1 study found:

  • 77% of patients getting raltegravir achieved a viral load of less than 400 copies of HIV RNA per milliliter of blood, compared with 41% of those on placebo.
  • On the stricter criterion of less than 50 copies, 61% of raltegravir patients met the target, compared with 33% of placebo patients.
  • Raltegravir patients had a mean increase of 83 CD4 cells, compared with 31 for those getting placebo.
  • All the comparisons were statistically significant at P

Adverse events were similar between the arms in both studies, Dr. Steigbigel said.