A study led by Roy T. Steigbigel, M.D., Professor of Medicine, Pathology, Microbiology and Pharmacological Sciences at Stony Brook University Medical Center, and colleagues worldwide demonstrated that raltegravir, a new medication to treat HIV infection, combined with other anti-HIV medications, provided superior suppression of HIV-1 in patients with highly resistant virus compared to placebo used with other anti-HIV medications. The results, reported in the July 24 edition of the New England Journal of Medicine, are for 48 weeks of therapy from two pivotal Phase III studies of 699 patients.
Resistance to antiretroviral therapies against HIV infection remains a problem for millions worldwide being treated for the infection. In fall 2007, the U.S. Food and Drug Administration granted approval of raltegravir for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients with HIV-1 strains resistant to multiple antiretrovial agents. The approval was based on analyses of viral load reductions and CD4 cell count increases from the start of treatment to 24 weeks in Phase III studies of the drug, which are ongoing. The 48-week data, reported in NEJM, adds to those studies.
“HIV disease is very complex and is especially difficult to manage in patients whose virus has become resistant to therapy,” says Dr. Steigbigel, Principal Investigator. “This new drug and approach, however, offers enormous hope for patients living with and being treated for HIV infection for many years.”
Dr. Steigbigel emphasizes that the 48-week results for raltegravir shows that when paired with other anti-HIV medicines, the drug effectively lowered the amount of virus in the blood to undetectable levels in 62 percent of the patients taking raltegravir plus other anti-HIV medicines, versus 33 percent of the patients receiving placebo plus other anti-HIV medicines. In total, 462 patients received the new drug and 237 received placebo.
Dr. Steigbigel also says the combination therapy with the drug helped the immune system to rebound in most patients, as CD4 cell counts were more than doubled in patients receiving raltegravir plus other anti-HIV medicines compared to patients receiving placebo plus other anti-HIV medicines.
The overall results stem from two major ongoing clinical trials (BENCHMRK-1 and BENCHMRK-2) that compares the drug in combination with other anti-HIV medicines to placebo plus other anti-HIV medicines. Patients in BENCHMRK-1 were enrolled in Europe, Asia, Australia, and South America. Patients in BENCHMRK-2 were enrolled in North and South America. Both of these studies are supported by Merck & Co, Inc., the manufacturer of raltegravir.
According to Co-investigator David Cooper, M.D., D.Sc., Professor of Medicine and Director of the National Centre in HIV Epidemiology and Clinical Research, University of South Wales, Sydney, Australia, results at week 48 were consistent across both BENCHMRK studies. Dr. Cooper also indicated that the efficacy shown after 48 weeks of treatment is consistent with observations at 24 weeks.
After 48 weeks, the therapeutic regimen was also well tolerated by patients. The analysis showed that only 0.9 percent of those receiving raltegravir discontinued therapy due to drug-related adverse events, compared to 0.4 percent receiving placebo. The most commonly reported drug-related side effects in patients receiving the raltegravir regimen included diarrhea, nausea, injection site pain or reaction and headache.
Fifteen sites worldwide participated in the study, with Stony Brook University Medical Center being the primary site in BENCHMRK-2. Other institutions providing patients and/or research data include: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales in Australia; Georgetown University Medical Center; University of North Carolina, Chapel Hill; Universidade Federal do Rio de Janeiro, Brazil; Aaron Diamond Research Center, The Rockefeller University, New York; University of Toronto in Canada; Emory University School of Medicine; Hospital Clinic-IDIBAPS, University of Barcelona, Spain; University of Bonn in Germany; Universite Pierre et Marie Curie in Paris, France; Hospital Bichat-Claude Benard, Paris, France; San Raffaele Scientific Institute, Milan, Italy; Hospital Germans Trias I Pujoy in Barcelona and Catalonia, Spain, and Merck Research Laboratories in Pennsylvania.