A quarter-century after the beginning of the AIDS epidemic, the rapid pace of scientific discovery has slowed to a crawl.
The early years of the epidemic were a sprint, as researchers isolated the virus that causes AIDS, developed rapid tests for the virus and found drugs that could block its replication -- culminating 10 years ago in the introduction of drug cocktails that made long-term survival possible.
Researchers were confident that an AIDS vaccine -- perhaps even a cure -- was just around the corner.
But that optimism evaporated as scientists began to untangle the mysteries of a virus far more intractable than any they had encountered before.
At least 96 U.S.-sponsored vaccine trials are underway, but experts agree that none is likely to yield a useful product.
Potential vaginal microbicides, which would allow women more control over their own risk of infection, remain out of reach.
Although new drugs are entering the marketplace, they are the result of old research.
"The low-hanging fruits have all been picked ... and we still face huge challenges," said Dr. David Ho of the Aaron Diamond AIDS Research Center in New York.
"This is not because of a lack of effort or because of a lack of money. It's just a fundamental problem posed by HIV."
Federal funding for HIV/AIDS research and treatment has grown from $200 million in 1985 to $21.7 billion this year.
UCLA's Dr. Andrew Saxon, one of the first to report the observation of the new disease 25 years ago, on June 5, 1981, added: "I don't think anyone appreciated how clever and difficult this virus could be.... I thought we would have had a vaccine by now and we would be entering the age of forgetfulness" about AIDS, just as the world has with smallpox and polio.
International agencies have been making strides in bringing drug therapy to poor areas and in developing prevention tools, but when it comes to fundamental research, "frankly, there isn't much new," said Dr. Jay Levy of UC San Francisco, who has studied the disease since it was identified.
"Aside from the terrible spread of the epidemic, there is simply not much news on the horizon."
World's No. 4 Cause of Death
In the United States, more than half a million people have died from complications arising from AIDS since 1981, and an estimated 15,000 will die this year, according to the federal Centers for Disease Control and Prevention. More than 1 million people in the U.S. are living with the virus, and 40,000 become infected each year.
The character of the epidemic has changed as well. A disease that once primarily struck gay white men and intravenous drug users has now largely become a plague of the poor and black.
African Americans, who make up about 13% of the U.S. population, account for half of new U.S. infections and a third of deaths. Black males are seven times as likely as white males to be infected with HIV; black females are 20 times as likely to be infected as white females.
Worldwide, the numbers are grimmer.
At least 25 million people have died from AIDS, and 2.8 million will die this year, according to the World Health Organization.
An estimated 38.6 million people carry the virus, and an additional 4.1 million are infected each year in what Dr. Kevin Fenton, head of AIDS programs at the CDC, called "one of the deadliest epidemics in human history."
The infection rate has slowed in a few countries, but population growth continues to fuel a rise in the number of total infections, according to data released last week by UNAIDS.
Only heart disease, stroke and respiratory infections kill more people worldwide each year.
"It is difficult to reflect back on the last 25 years, to understand how something that began so slowly and quietly and silently can now be the No. 4 cause of death in the world," Fenton said.
The epidemic has changed the world, making sex an activity to be feared, ruining the economies of many countries in sub-Saharan Africa, leaving millions of children parentless -- and often infected themselves -- and draining billions of dollars that could have been spent alleviating other afflictions.
"We are the last generation to know what life in a world without AIDS was really like," said Dr. James Curran, who was among the first at the CDC to study the disease and is now dean of Emory University's Rollins School of Public Health.
A Virus That Lies in Wait
Technically, AIDS has been around a lot longer than 25 years.
The human immunodeficiency virus is a mutated form of an ape virus that has presumably infected chimpanzees and other primates for possibly thousands of years. Most researchers believe the virus mutated and crossed into the human population from close contact between the two species, perhaps when hunters captured and ate the animals.