June 4, 2001 BOSTON (AP) - No one can say exactly when the AIDS epidemic began. But as good a date as any is June 5, 1981, when a government health bulletin carried a brief report of a strange outbreak in Los Angeles.
Over the previous eight months, five people had come down with a rare kind of pneumonia. The illness was caused by Pneumocystis carinii, a germ that ordinarily bothers only people with severely weakened immune systems. Yet these men seemed otherwise healthy, all in their 20s and 30s.
The write-up tersely ran through the details of lab findings and medical histories. But one clue jumped from the page: All five were homosexual.
The reason the men got sick was a mystery, but the report cautiously ventured a theory. Perhaps their immune defenses were harmed by some common exposure that left them vulnerable to usually harmless bugs. Perhaps it was a ``disease acquired through sexual contact.''
That guess, published in the Centers for Disease Control and Prevention's thin little Morbidity and Mortality Weekly Report, turned out to be exactly right. Those five were the first recognized cases of what was eventually known as acquired immune deficiency syndrome, AIDS, a disease that has gone on to kill more than 22 million people around the world.
As awesome as the human tragedy is, AIDS undoubtedly would be far worse without the monumental scientific campaign to find its source, to understand how it spreads and to create treatments. And in general, experts are optimistic that much more progress lies ahead.
Still, the victories seem bittersweet to some who were involved from the beginning. ``Science should be proud of itself but not happy,'' says Dr. Robert Gallo of the University of Maryland, co-discoverer of the AIDS virus. ``We have never had a moment of peaceful reflection when we could say, 'Aha! We did it.'''
Gallo's work in the early 1980s led to a screening test that removed AIDS from the blood supply, preventing spread through transfusions. It laid the foundation for the medicines that eventually changed AIDS from a death sentence to a chronic but survivable illness.
But Gallo's discovery did not result in a vaccine to keep people from getting AIDS, as some at the time optimistically predicted. And without a vaccine, the AIDS virus has spread explosively in some of the poorest parts of the world, especially Africa, home to two-thirds of the more than 36 million people now infected.
The possibility of an AIDS vaccine is just one of many unknowns as this epidemic enters its third decade. Breakthroughs cannot be predicted, nor can setbacks. But here are some of the outstanding questions - and possible answers - about the future of AIDS:
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Will there ever be an AIDS vaccine?
``Absolutely. The question is with how much effort and how much time,'' says Dr. Seth Berkley, president of the International AIDS Vaccine Initiative.
Over the years, scientists have often questioned whether such a thing could ever be done. Standard vaccines prompt the body to make antibodies that block infection. Unfortunately, humans seem unable to manufacture antibodies powerful enough to stop the AIDS virus. Without them, a vaccine seemed unlikely.
Now researchers are sounding more upbeat. In monkey tests, at least, several experimental vaccines seem to work well. While they may not prevent infection, they ward off AIDS by activating protective white blood cells called killer cells.
Typically, these vaccines mix genes taken from the AIDS virus with some other microbe, such as the one given as smallpox vaccine. Whether they will work in people is unknown. But if testing goes smoothly, Berkley said one of this new generation of vaccines could be available within five or six years.
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How many more Americans will catch the AIDS virus?
The CDC estimates that about 40,000 more Americans get infected each year. This number has held steady for the past decade and is down considerably from the mid to late 1980s, when 100,000 to 150,000 new infections occurred annually. Now, between 800,000 and 900,000 Americans have the virus.
About one-third of these infected people don't know it. The CDC says new infections could be cut in half if an all-out effort is made to identify more of these infected people, so they won't spread it.
The effective AIDS treatments in use since the mid-1990s may also change the course of the epidemic, although for better or worse is unclear. These drugs lower infected people's virus levels so they are less likely to pass on the virus. But they also make people more complacent about using condoms, increasing the risk of exposure.
``It's hard to tell whether these will cancel each other out,'' says Dr. Helene Gayle, the CDC's AIDS chief.
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Will there ever be a heterosexual epidemic of AIDS in the United States?
Not likely, says Gayle.
The heterosexual epidemic in Africa results largely from conditions that do not exist in industrialized countries. These include large-scale population shifts, little information about AIDS prevention, many migrant workers, widespread prostitution, deep reluctance to use condoms and frequent, untreated sexually transmitted diseases.
Still, heterosexual transmission is slowly increasing in the United States, largely to low-income black and Hispanic women. Among the things that put them at increased risk: exchanging sex for crack cocaine and having sex with drug addicts and bisexual men.
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How long can people with AIDS expect to live?
Fears that the highly effective AIDS drugs would quickly lose their punch have not come true. Most patients continue to do well, although long-term side effects are the biggest worry.
``I would like to believe people will be able to go for 35 or 40 years on antiviral drugs, but that's a lot to ask because of the dropout we see due to drug toxicity,'' says Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases.
Side effects that make some people quit treatment include an abnormal redistribution of body fat that leaves them with buffalo humps and skinny faces and extremities, along with a variety of metabolic complications, such as high blood sugar and cholesterol. Thinning bones are the latest anxiety.
``People are really questioning whether it's possible to have people on therapy decade after decade,'' says Dr. Joel Gallant of Johns Hopkins University.
Another concern is resistance: The virus can become immune to drugs, so patients must switch to different combinations. Eventually some run out of options. Nevertheless, they often stay healthy if they remain on treatment. The virus in their bodies is so weakened by its drug-resisting mutations that it does relatively little damage.
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Will there be new kinds of AIDS drugs?
The 14 AIDS drugs now on the market all attack one of two enzymes that the AIDS virus needs to reproduce. These are protease and reverse transcriptase. Drug companies are working on more that do the same thing, including some that work against strains of the virus that have grown resistant.
Also in testing are medicines that exploit entirely different targets in the virus life cycle. Likely to be approved next are drugs that bar the virus from attaching itself to blood cells, the first step in infection. The leader in this category is a drug from Trimeris Inc. code-named T-20, but others are being developed.
The virus makes about a dozen proteins, and all of them could potentially be blocked by medicines. Probably the most aggressively pursued of these is integrase, which the virus uses to insert its genes into cells' DNA, but drug developers say progress is slow.
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Will AIDS drugs get easier to take?
The pill burden has already eased considerably, and more improvement is likely.
When combination therapy started, people had to take 30 or so pills at various times a day, some with food, some with water, some on an empty stomach. The typical total has fallen to eight or 10 pills twice a day and is shrinking fast.
``The ideal is to get it down to something as simple as brushing your teeth or taking a once-a-day vitamin,'' says Dr. Eugene Sun of Abbott Laboratories.
Drug firms accomplish this largely by combining several medicines into one tablet. The easiest regimen so far is GlaxoSmithKline's triple-drug Trizivir. It's just one pill twice a day.
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Will AIDS ever be cured?
That's not likely, at least in any way that scientists can now envision. The reason: The virus gets into the immune system's memory, the long-lived cells that keep a record of all the microbes encountered over an individual's lifetime.
Dr. Robert Siliciano of Johns Hopkins University calculates it would take 73 years for these memory cells to die off completely, which ``essentially guarantees lifetime persistence of the virus.''
Still, some say this may be overly pessimistic. Dr. David Ho of the Aaron Diamond AIDS Research Center in New York City believes memory cells are much shorter lived, and their supply is constantly renewed by low-level infection. He is testing a super-potent drug combination intended to break this cycle, allowing all the AIDS-infected memory cells to die off, perhaps within three or four years.
Nevertheless, HIV may be hiding elsewhere in the body. So even if the strategy works, he cautions that AIDS will not necessarily be cured.
Copyright 2001 The Associated Press. All rights reserved.
