The drug inhibits the enzyme HIV-1 integrase, making it effective against multi-drug resistant strains of HIV-1 and particularly CCR5-tropic and CXCR4-tropic strains, said investigator David Cooper, MD, director, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
In a presentation on February 28th, Dr. Cooper discussed the study -- Blocking integrase in treatment Experienced patients with a Novel Compound against HIV: MeRcK, MK-0518 (BENCHMRK)-1 -- which included patients in Europe, Asia/Pacific, and Peru.
In addition, Roy T. Steigbigel, MD, professor of medicine, State University of New York at Stony Brook, Stony Brook, New York, United States, presented the findings from BENCHMRK-2, which involved patients from North America and the remainder of South America.
Both studies were randomised, double-blind, placebo-controlled comparisons in which patients took optimised background therapy (OBT) -- which could include enfuvirtide and darunavir -- plus raltegravir 400 mg twice daily or a placebo plus OBT.
The 2 studies combined a total of 462 patients taking raltegravir and 237 patients taking placebo. Key inclusion criteria were HIV RNA >1,000 copies/mL and documented genotypic or phenotypic resistance to at least 1 protease inhibitor, nucleoside reverse transcriptase inhibitor, and non-nucleoside reverse transcriptase inhibitor. Patients were evaluated at 16 weeks for viral load, CD4 count, and adverse effects.
The 2 studies yielded almost identical virological responses at 16 weeks: HIV RNA levels <400 copies/mL were achieved by 77% of patients in the raltegravir groups and 42% of the placebo groups (P < .001). CD4 levels increased by an average of 85 cells/mm3 from baseline among in the raltegravir groups and 36 cells/mm3 in the placebo groups (P < .001).
The incidence of adverse events did not differ significantly between the experimental and control groups in either study. In both studies, 1.7% of patients taking raltegravir discontinued due to adverse events compared with 3.4% of the placebo group in BENCHMRK-1 and 0.8% in BENCHMRK-2. Diarrhoea, injection site reactions, nausea, and headache were the most common complaints.
These findings suggest that raltegravir in combination with OBT exerts a potent and superior antiviral effect compared with placebo in patients who fail other antiviral therapies and have drug-resistant HIV, and is generally well tolerated, the investigators said.