Full Pipeline: Success of experimental AIDS drugs offers promise of future therapies

Three experimental drugs designed to thwart HIV have performed well in early tests on AIDS patients. If further testing supports these preliminary findings, the drugs might serve as able stand-ins for existing drugs in patients whose HIV becomes resistant to existing therapies.

The three new drugs–unveiled at the 10th Conference on Retrovirus and Opportunistic Infections in Boston last week–all hinder HIV but do so by distinctly different means. That’s a plus since anti-HIV drugs are often used in combination.

All three drugs are still years away from Food and Drug Administration approval. Nevertheless, notes John Mellors, a virologist at the University of Pittsburgh, these early findings suggest that “the pipeline of new drugs has an impressive number of new candidates. This is a bumper crop.”

He envisions these drugs as a “second generation” of therapies to replace drugs developed in the 1990s.

“We seem to be keeping up with the virus” as it develops resistance to some drugs, he says.

One of the new drugs is a monoclonal antibody called TNX-355 that binds to molecules on the surface of immune system T cells targeted by HIV. By occupying these molecules, or receptors, TNX-355 prevents the virus from spreading, according to tests in animals, says Daniel R. Kuritzkes, a virologist at Brigham and Women’s Hospital and Harvard Medical School in Boston.

Kuritzkes and his colleagues gave a single infusion of TNX-355 to 30 HIV-infected volunteers, 19 of whom were no longer benefiting from standard drug therapy. Patients receiving only a small dose of the drug showed little gain, but 10 of 12 getting a larger dose showed significant drops in virus counts and boosts in T cell counts in their blood for 2 to 3 weeks. Further tests are under way to determine the best dose and to assess how long the drug lasts, Kuritzkes says.

Meanwhile, scientists in Europe have designed a new protease inhibitor and tested it in HIV-positive patients. HIV in some AIDS patients has become impervious to the effects of currently prescribed protease inhibitors.

Keikawus Arasteh of the Vivantes Network for Health in Berlin reports that a drug called TMC114 reduced the virus presence by 90 percent in most of the 50 patients who received it for 2 weeks.

The third drug, called T-1249, is a fusion inhibitor that binds to the viral protein that forms a shell around HIV. As such it prevents HIV from fusing with a T cell–a prelude to viral invasion of the cell. G. Diego Miralles of Trimeris, a company in Durham, N.C., and his colleagues gave 24 patients two injections of T-1249 daily for 10 days. Subsequently, the amount of virus in the blood of two-thirds of the patients had dropped by roughly 90 percent, Miralles reports.

Many of the patients had been taking a fusion inhibitor called T-20, an experimental drug that will probably be approved for use soon by FDA, Miralles says. Some of these patients had already started to become resistant to T-20. The new fusion inhibitor may provide a replacement for T-20 in years to come, Miralles says.


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