A novel new class of HIV therapy known as integrase inhibitors currently in international multi-center double blinded  trial  including  Stony Brook University Medical Center and  the University of New Wales, Sydney, Australia, has proven effective in HIV-infected patients who had failed antiretroviral therapies (ARTs). Roy T. Steigbigel, M.D., professor of medicine, pathology, microbiology and pharmacology and Founder and Director, Comprehensive AIDS Center at Stony Brook, and colleagues, presented results after 16 weeks into the 156-week Phase III study at the 14th Annual Conference on Retroviruses and Opportunistic Infections (CROI) this month.

The investigational oral integrase inhibitor known as Raltegravir, formerly referred to as MK-0158, is under development by Merck & Co., Inc. The lead scientist for the development of this project at Merck Research Laboratories is Dr. Daria Hazuda, who received her PhD from the Department of Pharmacology at Stony Brook University.

Under the direction of Dr. Steigbigel, the Comprehensive AIDS Center at Stony Brook has been heavily involved in the clinical development of integrase inhibitors. Dr. Steigbigel enrolled the first patient in the world into the initial study for people with HIV infection. The Phase III study enrolled patients from two geographic areas: BENCHMRK-2 enrolled patients from North and South America, excluding Peru, and BENCHMRK-1 enrolled patients from Australia, Europe and Peru. At the end of the 16-week interval, 462 patients received Raltegravir in combination with optimized background therapy (OBT), and 237 patients received only OBT. Of those, 77 percent of patients who received Raltegravir with OBT achieved viral load reduction, to the end point of less than 400 copies of HIV RNA, compared to only 31 percent who received only OBT.
 
"We are very excited by the efficacy and tolerability of Raltegravir after 16 weeks of therapy in this group of patients who have resistance to at least one drug in each of the currently approved classes of HIV medications,” said Dr. Steigbigel.

According to the CDC, through 2005, 956,019 persons in the United States had been reported as having AIDS. Three states ? California, Florida, and New York ? reported 43% of the cumulative AIDS cases1. Despite the availability of drugs to treat HIV/AIDS, the epidemic continues. An estimated 40 million people are currently infected worldwide, and it is estimated that more than four million new infections occur worldwide annually. AIDS is one of the top causes of infectious disease-related mortality worldwide, responsible for approximately three million deaths each year.

Study Design
BENCHMRK-1 and BENCHMRK-2 are ongoing, 156-week, multi-center, triple-blind randomized placebo controlled studies that compare  Raltegravir in combination with OBT to placebo plus OBT in terms of reduction in HIV viral load, change from baseline in CD4 cell counts and evaluation of safety and tolerability.  Patients who entered the study had failed antiretroviral therapies as documented by HIV RNA of greater than 1000 copies/mL on stable ARTs for at least two months and were infected with HIV resistant to one or more drugs in each of the three oral classes of ARTs [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs)].

Patients received Raltegravir 400mg or placebo, each dosed orally twice daily in combination with OBT.  OBT was selected based on patients' prior treatment history and results from HIV resistance testing.  In order to allow for the best possible treatment regimen to be constructed for each patient, darunavir and tipranavir, which were investigational ARTs in many countries at the time of this study were allowed to be included in OBT.  In addition, patients who were co-infected with Hepatitis B or C were allowed to enroll in these studies.
 For more information on the ongoing BENCHMRK-2 trial, call Stony Brook University Medical Center HealthConnect? at (631) 444-4000.