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Analysis: AIDS Research Pipeline Bursting

The research continues...
by Ed Susman
Toronto (UPI) Aug 17, 2006
Over the last decade, critics of the International AIDS Conference -- witnesses to an increasing agenda of politics, policy and protest -- have asked, "Where's the science?" Mark Wainberg, director of the McGill University AIDS Research Center and program chairman of the 16th International AIDS Conference in Toronto, said, "You tell everyone, this is the year we brought science back to the conference."

That science was showcased in a marathon session of late breaking researcher papers, spotlighting what patients with human immunodeficiency virus (HIV) infection can look forward to in the next couple of years.

And, as with all investigational treatments, some appear more promising than others.

"Some of these drugs are going to help change peoples lives," Wainberg told United Press International on Friday, the closing day of the week-long conference that drew nearly 30,000 people to Toronto.

One of the key drugs on display was Merck's experimental MK0518, an HIV integrase inhibitor. Integrase is one of the three enzymes that HIV uses to take over a cell and turn it into a factory to produce more viruses.

Wainberg said integrase may be the key enzyme that will prevent the virus from replicating, and the study reported by Martin Markowitz, clinical director of the Aaron Diamond AIDS Research Center at Rockefeller University, New York, indicates that treatment with the new drug rapidly drives the virus that causes AIDS out of the blood stream.

In reporting results of a 24-week trial of MK-0518, Markowitz compared the investigative compound against the standard-of-care three-drug combination based on the non-nucleoside reverse transciptase inhibitor efavirenz (Sustiva). Thirty patients were randomly assigned to receive the Sustiva regimen.

That regimen was pitted against four different doses of MK-0518 taken by four groups of 30 patients.

Every dose of MK-0518 was able to subdue the virus and reduce its presence in the blood stream to undetectable levels by week 24. The Sustiva-based therapy also was able to perform as well.

The difference between the drugs: Significantly more MK-0518 patients were at undetectable levels at week four and week eight than those on Sustiva. It showed that MK-0518 gets the job done earlier.

"This integrase inhibitor is the real thing," Stefano Vella, director of drug research and evaluation at Italy's NIH-counterpart, Insituto Superiore di Saniti, told UPI. "We will be able to use this drug to rapidly reduce HIV. The data are compelling."

MK-0518, and oral drug, inhibits the insertion of the HIV viral DNA into human DNA. Inhibiting integrase from performing this essential function blocks the ability of the virus to replicate and infect new cells. There are several drugs in use that inhibit the other two enzymes -- protease and reverse transcriptase -- but there are no approved drugs that inhibit integrase.

Other drugs featured at the same three-hour session try to prevent HIV from entering the cells. Maraviroc blocks the CCR5-receptor on the surface of he cells. It is through the CCR5-receptor doorway that the virus invades the cell and sets up shop.

However, Howard Mayer, a researcher for Pfizer Global Research and Development, new London, Conn., said results of the phase 2 preliminary study were mixed.

The drug didn't appear to perform better than placebo, but levels of a key indicator of how well the patient's immune system is performing improved. Mayer said that both doses of maraviroc resulted in significantly more CD4-positive cells being produced.

"This requires further investigation," he said.

Another CCR5-inhibitor, vicriviroc, also showed puzzling results. Roy Gulick, professor of medicine at the Weill College of Medicine at Cornell University in New York, reported that patients treated with the investigative drug were able to drive down the amount of circulating virus in the blood between 95 percent to 98 percent, indicating a strong anti-HIV effect.

However, among the 118 people in the study, six people who had ever taken vicriviroc developed various forms of cancer. While cancers are part of the background risk of HIV infection, researchers were uncertain why there were such a relatively high percentage of malignancies experienced by patients in the study.

Another experimental drug, TNX-355, being developed by Tanox of Houston, Texas, aims at occupying a receptor on the CD4-positive cell, denying the virus from attaching to its target.

Robin Hardwicke, a researcher at the University of Texas Health Science Center, Houston, said that treatment with the injected drug reduced the amount of circulating virus from about 65 percent to more than 90 percent depending upon the dose of the drug.

Research with the drug is continuing.

All of the experimental drugs are delivered in combination or on top of current best available treatments, the researchers said.

Source: United Press International

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Drugs Defeat Resistant AIDS
Toronto (UPI) Aug 15, 2006
Almost half the patients infected with highly resistant strains of human immunodeficiency virus (HIV) suppressed the microbe that causes AIDS to undetectable levels in their blood when the new anti-AIDS drug darunavir (Prezista)was added to their multi-drug regimens.







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