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©World National / Roger-Luc Chayer

HIV Develops Resistance to Experimental Drug

NEW YORK (Reuters Health) - An experimental AIDS ( news - web sites) drug called T-20, which researchers hope will benefit people whose HIV ( news - web sites) infections have become resistant to other medications, may itself sometimes cause HIV resistance to develop, the results of a new study suggest.

But the resistance developed in a study of patients taking T-20 alone, not in combination with other medications. Recently, the Swiss healthcare group Roche Holding AG, which is developing the drug with North Carolina-based Trimeris, Inc., reported encouraging results of studies of T-20 used in combination with other AIDS drugs.

"Both studies indicate that T-20 significantly enhances the activity of HIV combination therapy," Dr. Dani Bolognesi, the chief executive officer and chief scientific officer of Trimeris, told Reuters Health.

Bolognesi pointed out that the cases of HIV resistance developed in an early-phase trial designed to test the safety of the drug in humans. He noted that HIV developed resistance only in patients taking a lower dose than is being tested in later trials of T-20, which are still ongoing. Resistant viruses have not developed in those studies, according to Bolognesi. Further details of T-20 studies will be presented later this summer at an international AIDS meeting in Spain, he said.

T-20 is the first of a class of AIDS drugs called fusion inhibitors. Unlike current drugs that target HIV once it has already entered cells, fusion inhibitors work by keeping HIV from entering cells in the first place.

In the study, Dr. John C. Kappes and colleagues at the University of Alabama at Birmingham studied 16 people with HIV. The patients took 3 milligrams (mg), 10 mg, 30 mg or 100 mg of T-20 twice a day for 2 weeks.

In patients taking the two lowest doses, there was no noticeable effect on the level of HIV in the blood, known as the viral load. In all patients taking the highest dose, however, viral load dropped below detectable levels.

The problems with resistance developed in patients taking the 30-mg dose. These patients experienced some decline in viral load, but it was not as large as the drop seen in the 100-mg group. At the end of the study, though, the researchers detected HIV mutations in two of the four patients in the 30-mg group.

"Our study of patients receiving T-20 monotherapy provided the first evidence for the rapid emergence of clinical resistance to a novel class of entry inhibitors," Kappes told Reuters Health.

"These findings," according to Kappes, "are highly relevant to ongoing and future treatment strategies involving these agents."

In the report, Kappes and his colleagues note that other types of HIV medications, including powerful drugs called protease inhibitors, may trigger resistance when taken alone. Standard practice is to treat HIV infection with a combination of several drugs. This strategy helps keep HIV from changing its structure to make it more resistant to the effects of medications.

The study was funded by the National Institutes of Health ( news - web sites), but Trimeris provided the drug for the study.

SOURCE: Antimicrobial Agents and Chemotherapy 2002;46:1896-1905.