ICAAC: Integrase Inhibitor Effective for HIV Patients with Multi-drug Resistant Disease

CHICAGO, Sept. 18 -- The investigative integrase inhibitor raltegravir (Isentress) suppresses the viral load to undetectable levels in at least half of HIV patients with virus resistant to three drug classes, researchers said here. All doses of raltegravir were superior to an optimized background of available antiretrovirals, Jose Gatell, M.D., of the University of Barcelona told attendees at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
"The findings at 48 weeks are consistent with the 24-week results and what we know to date about the drug's efficacy and tolerability profile," he said.
The 24-week results were presented at a meeting in Brazil earlier this year, as reported in MedPageToday.com (See: Investigational Integrase Inhibitor Hits HIV Hard).
Dr. Gatell and colleagues randomized 178 patients to three doses of raltegravir and placebo. There were 43 patients assigned to the 200 mg dose of raltegravir twice a day; 465 patients received 400 mg daily; 45 patients received 600 mg daily; and 45 patients received placebo. These were in addition to the best optimized drug regimen available.
Each of the patients had circulating levels of at least 5,000 copies of HIV RNA/mL, had CD4-postive cell counts greater than 50 cells/cubic mm, and documented resistance to three classes of oral antiretroviral therapies - protease inhibitors, nucleoside reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors.
On average, the patients were about 43 years of age and about 85% were men. They had been taking antiretroviral medication for an average of 10 years. After the 24-week study, patients who had been on just the optimized background treatment were allowed to join an open-label extension.
Among patients taking raltegravir, 64% to 71% of patients had suppressed viral loads to undetectable levels using the 400-copy assay. The differences between doses were not considered significant. Approximately, 46% to 64% of patients suppressed virus to undetectable levels using the 50-copy assay.
"In HIV-infected patients failing therapy with triple-class resistant virus, raltegravir in combination with optimized background therapy has potent, superior and durable antiretroviral activity," Dr. Gatell said.
In addition, he said the treatment with raltegravir was well tolerated. "There were very few adverse experiences leading to discontinuations," he said.
"The long-term data shown here reinforces what we know about HIV treatment," said Roy Gulick, M.D., associate professor of medicine at the Weill Medical College of Cornell University in New York, "and that if a new drug is going to be successful it requires that it be used with a background therapy that is also effective."
Dr. Gulick noted that most of the virological failures with raltegravir occurred in patients with a background regimen that had no drugs to which the virus was not resistant. Dr. Gatell reported that two-thirds of the 38 patients who experienced virological failure with raltegravir had background regimens without any drugs that were still effective against the virus.
Merck has filed for approval of raltegravir with the FDA, which has designated the drug for priority review. A decision is expected by mid-October.
Dr. Gatell disclosed possible financial conflicts of interest with Merck, Abbott, Roche, GlaxoSmithKline, Bristol-Myers Squibb, Tibotec, Virgo, Boehringer Ingelheim, and Pfizer.
Dr. Gulick disclosed possible financial conflicts of interest with Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline Kline and Merck. Primary source: Abstracts: 47th Interscience Conference on Animicrobial Agents and Chemotherapy, Sept.17-20, 2007
Source reference: B Grinnsztejn, et al "48 Week Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-Class Resistant Virus" Abstract H-713: 47th Interscience Conference on Animicrobial Agents and Chemotherapy, Sept.17-20, 2007, p. 295.