New study results demonstrated sustained anti-HIV effects of Crixivan(R) (indinavir sulfate) in triple combination with AZT(1) and 3TC(2) in suppressing HIV to below the level of detection (500 copies/mL) in 78 percent of patients (25/32) for nearly two years (100 weeks).

Two years after early data presented at the last world AIDS conference in Vancouver from this landmark study (Merck study 035) helped to revolutionize the treatment of HIV and marked a turning point in the battle against AIDS, longer-term open-label results published in a special HIV edition of the Journal of the American Medical Association (JAMA) were released at the 12th World AIDS Conference Saturday.

Merck Study 035: Sustained Anti-HIV Effect with Crixivan

"Merck's study 035 is the longest reported combination study with a potent HIV protease inhibitor that achieves the goal of HIV treatment: long-term suppression of the virus," said Roy M. Gulick, M.D., assistant professor of medicine, Cornell University Medical College and an investigator in the study.

The JAMA article shows that among those patients who initiated triple therapy simultaneously, after 100 weeks of treatment with Crixivan, AZT and 3TC, 78 percent of patients (25/32) had undetectable levels of HIV (under 500 copies/mL) and 66 percent (21/32) had even lower levels of virus, less than 50 copies/mL using an investigational assay. Conversely, only 30% of patients who started with the combined therapy of AZT plus 3TC and added Crixivan six months later maintained undetectable levels of HIV (less than 500 copies/mL). The study was modified after at least 24 weeks of blinded therapy to provide open-label three drug therapy with follow-up through 100 weeks. The study is unusual among trials with protease inhibitors in that 85 percent (28/33) of patients who originally enrolled in the triple therapy group stayed in the study for over two years.

Three-Drug Combination with Crixivan Started Simultaneously = Most Effective HIV Suppression

"Study 035 answers one of the most important strategic treatment questions facing physicians today -- how to start therapy to get the most effective results," said Dr. Gulick. "We now have definitive data that delayed sequential therapy for HIV was less effective than initiating simultaneous treatment with a three-drug combination that included a potent protease inhibitor."

Referring to past reports of failed anti-HIV regimens, Dr. Gulick said, "We also have persuasive evidence that shows that adding-on medications to existing treatments may have, in fact, played a major part in causing treatment failures." Researchers have speculated that sequential treatment, rather than simultaneous initiation of anti-HIV medications, can result in incomplete viral suppression and, consequently, the development of new, treatment-resistant virus.

Three-Drug Combination with Crixivan Confirms U.S. Treatment Guidelines

"No other study has demonstrated so definitively how simultaneous initiation of combination treatment is clearly a patient's best chance at suppressing HIV," said Dr. Gulick. "The extended results of study 035 provides some of the strongest support to date for the HIV treatment strategies recommended in the guidelines recently issued in the United States," said Dr. Gulick.

In late 1997, the U.S. Department of Health and Human Services (HHS) issued recommendations that are a guide for U.S. physicians on how to use antiretroviral medications most effectively to maximize treatment outcomes for patients. The guidelines strongly recommend starting first-line therapy -- or changing failing therapy -- with a simultaneous combination that consists of a potent protease inhibitor, such as Crixivan, and two nucleoside reverse transcriptase inhibitors, such as AZT and 3TC. The U.S. guidelines have rated Crixivan in the A1 category.

"What do these advances mean for patients?" asked Dr. Gulick, "Anyone who's HIV infected needs to know that there are good treatments, that these treatments are now showing two years of sustained effects and they need to ask their doctors about how this information may apply to them."

Crixivan is a protease inhibitor that fights HIV. Crixivan can help reduce the chance of illnesses and death associated with HIV. Crixivan can also help lower the amount of HIV in the body (called "viral load") and raise CD4 (T) cell count. Some patients may not experience these effects. Crixivan is not a cure for HIV or AIDS.

Two Years and Counting: Most Patients Below Detectable

Merck's study 035 included 97 HIV positive patients who had not been previously treated with 3TC or a protease inhibitor but had received AZT, and with viral load levels at least 20,000 copies/mL and CD4 cell counts between 50 - 400 mm(3). Patients were initially randomized to receive one of three antiretroviral regimens: Crixivan by itself (800 mg every 8 hours), or a combination of AZT (200 mg every 12 hours) and 3TC (150 mg every 12 hours), or the combination of the three drugs.

After 24 weeks of randomized treatment, all patients were changed to open- label therapy with Crixivan and AZT plus 3TC and were followed for a total of 100 weeks. This provided an opportunity to compare the use of three-drug antiretroviral treatment started simultaneously with the same treatment regimen started sequentially. Sustained viral suppression and increased CD4 cell counts were compared between the simultaneous and sequential triple therapy groups.

Fifty-two week data from the study were first published in the New England Journal of Medicine in September 1997.

Crixivan -- Cautionary Information

There are some common medications and AIDS-related medications that should not be taken with Crixivan. Crixivan should not be administered concurrently with terfenadine, cisapride, astemiozole, triazolam, midazolam or ergot derivatives. Crixivan can be taken on an empty stomach or with a light meal. Crixivan is generally well-tolerated. There are side effects associated with protease inhibitors in general and Crixivan in particular. Some patients treated with Crixivan may develop kidney stones. For some, this can lead to more severe kidney problems including kidney failure. Drinking at least six glasses of water a day may help reduce the chance of forming a kidney stone.

Other side effects reported include rapid breakdown of red blood cells and liver problems. As with other protease inhibitors, increased bleeding in some patients with hemophilia and increased blood sugar levels or diabetes have been reported.

About Crixivan

Crixivan is now approved in more than 80 countries. Crixivan is the most widely prescribed protease inhibitor in the world.

Merck has developed, with the American Dietetic Association, a list of foods, light meals or snacks that can be taken with Crixivan. Additional information about Crixivan is available on Merck's web site, www.crixivan.com. Following is a copy of the prescribing information about Crixivan.

Merck & Co., Inc., is a global research-driven pharmaceutical company that discovers, develops, manufactures and markets a broad range of human and animal health products, directly and through its joint ventures, and provides pharmaceutical benefit services through Merck-Medco Managed Care.

Full prescribing information is available by calling 800-753-0352, ext. 706.