BUSINESS WIRE - 44 Montgomery St, 39th Floor, San Francisco, CA 94104; Tel: (415) 986-4422; FAX: (415) 788-5335 - 29 September 1997.

(ADVANCE) TORONTO--(BW HealthWire)--Sept. 29, 1997--In a retrospective study of 136 HIV-infected patients who took potent protease inhibitor therapy, more than half of the patients (53 percent) developed evidence of drug failure on the treatment, UC San Francisco researchers have reported.

"This was a 'real world' study," said Steven Deeks, M.D., UCSF assistant professor of medicine in the UCSF AIDS Program at the UCSF-affiliated San Francisco General Hospital. "We were looking at patients who were not the idealized research patient typically found in a clinical trial, but the average patient seen by our physicians in a public health hospital."

"We are concerned that the long-term efficacy of these drugs may be limited, particularly for patients who begin treatment with advanced HIV disease and for people who have been on multiple drugs in the past," Deeks said.

Deeks and his colleagues found that the success rate for the clinic patients in the study was much lower than that reported in clinical trials. In their study, 53 percent of the patients had evidence of treatment failure after at least six months of therapy. In contrast, failure rates in controlled clinical trials are usually in the 10 percent to 20 percent range.

"Clinical trials tend to enroll patients who are healthy, who haven't been on much therapy in the past and who are highly motivated; they are not the typical patient," Deeks said. The study was presented today (Sept. 29) at the 37th meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

In a detailed analysis, the researchers found that those who failed treatment were patients who had one or more risk factors. The risk factors included having begun therapy when the patient had a low T cell count, had a high viral load, had already been on antiretroviral drugs in the past, or had problems in complying with the treatment regimen, Deeks said. (T cells are the body's infection-fighting cells that are killed off by infection with HIV. A high viral load means the infected person has large quantities of HIV circulating in the blood.)

According to the researchers, their data supports recent guidelines recommending that HIV-positive patients initiate triple drug therapy with two nucleoside analogs and a protease inhibitor at the same time rather than using the weaker nucleoside analogs to begin with and adding a protease inhibitor later.

"Our data supports the 'hit hard, hit early' philosophy recently recommended by two different panels of experts," Deeks said. "Treatment should begin before the patient's T cells drop to low levels."

The researchers reviewed medical charts of approximately 450 patients who were seen at SFGH from March 1996 through March 1997. Nearly 200 of these patients were treated with a protease inhibitor, such as indinavir or ritonavir, in combination with at least one and often two other antiretroviral drugs.

Ten of the 200 patients died, 25 were unable to tolerate the drugs, 136 had long term follow-up, and the remainder had limited follow-up, so were not included in the final analysis.

Deeks emphasized that their results should be understood in the context that most of the patients were in relatively advanced stages of HIV disease. "We don't know the long-term activity of protease inhibitors for healthy people who begin them in combination with other drugs, as is currently recommended," he said.

In a companion presentation, Deeks presented data at the conference indicating that when a patient fails treatment with a first protease inhibitor, success with a second protease inhibitor may be limited. In this second study, 16 patients who failed one protease inhibitor were treated with an aggressive combination of two powerful protease inhibitors and two other antiretroviral drugs. Most of the 16 patients had a limited and short-lived response to the drugs, Deeks said. "The finding suggests that there is cross resistance among protease inhibitors and that patients may have only one shot at achieving long-term viral suppression," he said.

"In our clinic we appear to be seeing the epidemic split in two. About half of our patients will see a long-term, possibly permanent, response to these drugs while the other half may begin to exhibit disease progression again," Deeks said. "The pharmaceutical industry, the government and all researchers need to remain vigilant and continue to develop new therapeutic options for HIV positive patients."

Co-authors of the study are Philip (Peter) Cohen, M.D., MPH, UCSF associate professor of medicine/SFGH; Robert Grant, M.D., and Rick Loftus, Gladstone Institute of Virology and Immunology.

(End of advance for release 9 a.m. PDT Sept. 29.)

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CONTACT: UCSF News Services Alice Trinkl, 415/476-3804

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