Dozens of experimental medicines and vaccines are being studied to see which will help patients live longer and maybe even prevent infection. Clinics at Duke University and the University of North Carolina at Chapel Hill, two of the largest HIV/AIDS treatment centers in the country, are buzzing with patients testing many of the new medicines.

"We are very, very busy," said Dr. Charles van der Horst, an AIDS specialist at UNC-CH. "We're doing tons of studies."

But most of the new treatments and vaccines were discovered elsewhere.

The Triangle dominated HIV/AIDS drug research for nearly three decades. But now the area's reputation is at stake as local pharmaceutical companies such as GlaxoSmithKline and Trimeris struggle with research setbacks, corporate restructuring and tougher competition.

More than 70 new medicines and vaccines are being tested in patients and healthy volunteers nationwide; about half of them are drugs that target the human immunodeficiency virus, according to a 2006 survey by the Pharmaceutical Research and Manufacturers of America, the industry trade group known as PhrMA.

Of those, only seven are being developed by companies in the Triangle, and none is in late-stage testing.

That's a far cry from 2001, when GSK was the market leader with Combivir, and it was in the final stages of developing Trizivir, the first three-pills-in-one combination. Smaller Triangle companies, Trimeris and Triangle Pharmaceuticals, also had HIV/AIDS drugs in final testing, and AlphaVax had begun working on an HIV vaccine.

But the Triangle's prospects started to sour in 2003 when Triangle Pharmaceuticals was bought by California-based Gilead, and the area's most promising new HIV/AIDS drugs -- Trizivir and Fuzeon -- flopped in the marketplace.

Now six years after the Triangle was hailed as the epicenter of HIV/AIDS drug research, efforts to combat the disease continue in the Triangle, but the virus has become smarter.

An HIV infection is no longer a death sentence, as the number of approved treatments approaches 90. But the virus is becoming resistant to an increasing number of drugs and is spinning off different strains.

"Now, [HIV drug development] is a tougher nut to crack," said Dr. Garheng Kong of Intersouth Partners, a Durham venture capital firm that invests in drug research.

GSK's reign ended last year, with a lack of next-generation products coming to market.

The British drug maker, which still conducts most of its HIV/AIDS drug research in the Triangle, is working hard to find breakthroughs, said Linda Bannister, a pharmaceutical analyst with Edward Jones. But shelving its most advanced next-generation HIV/AIDS pill 18 months ago because of serious side effects left GSK with two drugs that were discovered by researchers at other companies and two HIV vaccines that will require years of additional testing to see whether they work.

"GSK has done precious little invention in HIV," said Michael Weinstein, president of AIDS Healthcare Foundation, a Los Angeles advocacy organization. "They've gone from dominant force to being yesterday's news."

Successes in other therapeutic areas, such as breast cancer, have captured GSK's attention more than HIV/AIDS, said Bannister, who projected that the company's sales from HIV/AIDS treatments will continue to decline.

Five of the eight HIV/AIDS drugs that GSK sells will lose patent protection in the next seven years, which could cost the company half of its HIV/AIDS market share, according to market research firm Datamonitor.

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