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

[Snowy Owl]

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

By Ed Susman, Contributing Writer, MedPage Today
Reviewed by Zsofia Szep, MD; Infectious Diseases Division, University of Pennsylvania School of Medicine.
September 18, 2007
http://www.medpagetoday.com/MeetingCoverage/ICAACMeeting/tb/6718

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.

Action Points

• Explain to interested patients that optimized background medication remains important for treatment of HIV-infected patients.
• Note that this study was published as an abstract at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

"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.


<table bgcolor="#a0d7f6" border="1" cellspacing="0" hspace="1"> <tbody><tr><td>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.
</td></tr></tbody></table>

Complete ICAAC Coverage

Primary source: Abstracts: 47^th 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: 47^th Interscience Conference on Animicrobial Agents and Chemotherapy, Sept.17-20, 2007, p. 295.

 

[AlaskaDenise]

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

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

FDA approves Merck's new HIV drug

Merck & Co. said Friday the Food and Drug Administration approved its Isentress twice-daily tablets as a treatment for patients who have strains of the HIV virus resistant to multiple antiretroviral drugs.

Isentress is the first of a new class of antiretroviral drugs called integrase inhibitors, which work to prevent the virus from inserting its DNA into human DNA, thereby stunting its ability to replicate and infect new cells.

Drugs currently on the market inhibit two other enzymes critical to the HIV replication process -- protease and reverse transcriptase -- but Merck says Isentress is the only approved treatment which inhibits the integrase enzyme.

The FDAs approval was based on a 24-week analysis of clinical trials in which nearly 700 patients with HIV strains resistant to most medications received Isentress in combination with other anti-virals. Those treated saw significant reductions in HIV RNA viral load and increased CD4 cell counts.

Merck said it worked closely with the HIV community on pricing, and has priced Isentress at $27 per day, or less than $10,000 a year.

In 2006, over one million Americans were living with HIV/AIDS and it is estimated that approximately 40,000 new cases of HIV/AIDS are diagnosed each year in the United States. Worldwide, an estimated 40 million people are infected with HIV/AIDS, and more than four million new infections occurred last year.

"As the AIDS crisis continues, new drugs like Isentress are needed, which target the virus in unique ways," said Ben Cheng, deputy director, Forum for Collaborative HIV Research. "The HIV advocacy community is really excited and encouraged by this new treatment."

http://www.businessweek.com/ap/financialnews/D8S7VNF82.htm