A shot that helps keep AIDS-infected monkeys alive may offer the best clues yet about how to make an effective HIV vaccine, researchers reported on Thursday.

The experiment provided important clues about how the AIDS virus destroys the immune system, and how to track the health of infected people, the researchers said.

"A vaccine of this type does not appear to prevent infection," Dr. Norman Letvin of Harvard Medical School in Boston, who helped lead the study, said in a telephone interview. What the vaccine may do, he said, is help infected people live longer without becoming ill.

The study, published 25 years after the first medical description of AIDS was released by the U.S. Centers for Disease Control and Prevention, highlights the biggest challenge of the pandemic - how to prevent infection.

In the 1980s, medical researchers believed it would be easy to make a vaccine against the virus. But more than $3 billion later, no one has an effective vaccine, although more than 30 different ones are in various stages of testing in people.

The problem is that the virus, which has killed more than 25 million people since 1981, attacks the immune system cells that usually defend against infection. It mutates constantly, making a moving target.

Letvin's team vaccinated monkeys against simian immunodeficiency virus or SIV, using monkeys and a monkey version of the AIDS virus that are considered the closest model of human infection.

Most vaccines stimulate the body to produce antibodies, which help orchestrate an immune response against a particular virus or bacteria. But that approach does not work for HIV.

Scientists believe a second type of immune response, called cell-mediated immune response, is necessary to fight the AIDS virus. Letvin's team tested a vaccine that triggers a strong immune response by those cells, known as T-cells.

TRIPLING LIFE SPAN

Monkeys who got the SIV vaccine lived much longer when they were later infected with HIV, living up to 900 days, while unvaccinated monkeys died on average within 300 days, Letvin's team reports in Friday's issue of the journal Science.

"There are two human vaccines that are similar to this that are now going forward into advanced efficacy trials," Letvin said. One is being developed by the U.S. National Institutes of Health and the other by Merck and Co.

The trial gives researchers something to look for in their human volunteers - who obviously cannot be deliberately infected with the AIDS virus as the monkeys were.

"The magnitude of the immune response that is generated by vaccination predicts how long the animals will live after infection. The more potent the immune response after injection, the longer the monkey lived," Letvin said.

Also, how much virus is in the blood, called viral load, is not particularly important, Letvin said. That runs counter to many assumptions among AIDS experts.

"What is useful (to measure) is the subpopulation of helper CD4 T cells - the central memory CD4 T lymphocyte population," Letvin said.

"This tells us something profoundly important about why AIDS progresses clinically - the preservation of this central memory population of CD4 helper lymphocytes appears to be absolutely crucial for maintaining immunological competence," Letvin said.

Left untreated, the AIDS virus gradually destroys the immune system and patients die on average within nine to 10 years of various infections or cancer.

Drug cocktails can delay that but they are often expensive or unavailable to people in the most badly affected countries.

The 25-year fight against AIDS has been good to Gilead Sciences Inc., a Bay Area biotechnology company that makes the world's hottest-selling HIV treatment.

The popularity of the treatment, Truvada, is soaring because it has almost no side effects and requires patients to take only a single pill once a day. With close to two dozen AIDS drugs on the market, the company that once had Defense Secretary Donald Rumsfeld as its chairman is an industry leader. Its stock price has nearly doubled since Truvada was approved on Aug. 2, 2004.

But success on Wall Street hasn't insulated Gilead from complaints that it isn't doing enough to combat the disease where it hits hardest: in the Third World.

"For a company that prides itself on their access program, they have been irresponsible in getting the drug out," said David Bryden of the Global Aids Alliance, a Washington-based advocacy group that organized a small protest outside Gilead's annual shareholders meeting in May.

Truvada's chief asset is that it includes two drugs — known generically as tenofovir and emtricitabine — in a single pill.

That's a dramatic departure from a few years ago, when HIV-positive patients carried small alarm clocks to remind them to take their myriad pills at the right time. The onerous dosing regimen and often nasty side effects dissuaded many patients from taking their medication.

"Truvada is revolutionary because simplicity leads to better outcomes," said Gilead Chief Financial Officer John Milligan, a former Gilead scientist who has been with the company for 16 years.

Doctors now prescribe Truvada to 60 percent of all newly diagnosed HIV cases in the United States. The two drugs in Truvada will ring up close to $2 billion in sales this year individually or combined in the blue, teardrop shaped pill. That's about half the estimated global AIDS market of about $4 billion.

"The drug clearly dominates its class," said Sharon Seiler, an analyst at Punk, Ziegel who sent a note to her clients Tuesday advising them to buy the company's stock. "The company has a lot of credibility."

The Foster City company is expected to get an even bigger boost when the Food and Drug Administration approves a new, three-drug combination of Truvada and Bristol-Myers Squibb Co.'s popular Sustiva. Because all three drugs are already on the market, FDA approval is widely expected this year.

But the 1 million Americans estimated to be infected with HIV are a fraction of the 40 million people worldwide living with the AIDS virus. Nearly 25 million of those are in Africa south of the Sahara.

Gilead acknowledges a responsibility to make its drugs available to the developing world and has touted its Gilead Access Program in several press releases since it was unveiled nearly three years ago. In April 2003, Gilead said it would make tenofovir available in all of Africa plus dozens of other developing nations "at no profit."

But medical and AIDS advocacy groups say the access program is little more than an empty promise. In February, the international humanitarian group Doctors Without Borders issued a scathing report that concluded the company has failed to gain regulatory approval in nearly all the impoverished countries it promised to serve.

On the same day in New Delhi, activists protested Gilead's plans to patent tenofovir in India, which has the most AIDS cases of any country. Close to 6 million people are living with the AIDS virus in India. Tenofovir has been available generically in India since last year and activists fear the cheaper drugs will disappear if Gilead is granted a patent.

"We certainly believe in intellectual property around the world," Gilead chief executive John Martin said. "On principal we believe that our product should be patented."

What's more, Martin said, critics should give Gilead a chance to get its drugs approved by government regulators in each of the poor countries where it has promised access. Several countries having been reviewing the company's applications for two years, he said.

"We are one small company in a big world where billions of dollars are being put at the problem of AIDS," Martin said. "I am proud of what we have been able to accomplish and look forward to what we'll do in the future."