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Purposely infected to spare others from AIDS

Charles Farthing is medical director of the Los Angeles-based AIDS Healthcare Foundation.

Eight months ago, I volunteered to take part in a trial to test a proposed vaccine for AIDS. If the study goes ahead, in the next year or two I'll be injected with a weakened strain of HIV, the virus that causes AIDS, and then undergo a series of blood tests to assess how the virus is behaving.

Since I made the decision to volunteer, I've been joined by about 300 physicians, AIDS researchers, AIDS activists and other public-spirited citizens, all with the same intention. But there has also been a far more cautious reaction from physicians who fear that the vaccine will damage our immune systems and actually cause AIDS.

I don't consider volunteering an act of heroism. Right now, I believe a vaccine is the only realistic means of combating the worldwide AIDS epidemic. I don't think the risks to my health from the proposed vaccine are great. But if they are, it's only right that scientists and doctors should be among the first to find that out. That's what they've done in the past, and that's what we should continue to do.

In a long tradition that is often associated with the 19th century French chemist Louis Pasteur, researchers have given themselves hookworm and gonorrhea, stomach ulcers and staphylococcal infections in order to study those diseases. They've ingested belladonna and hemlock, opium and digitalis in the name of finding relief or a cure for others. And they've sought preventive vaccines against diseases like rabies and polio.

Now it's time for AIDS researchers and doctors to follow suit. In many ways, we're in a better position than our predecessors. When the first volunteers took Albert Sabin's oral polio vaccine in the 1950s, for example, they were exposing themselves to a disease for which there was _ and still is _ no known treatment. That's not true of AIDS today; we now have highly effective drug therapy.

To some people, this must seem a strange time to stress the need for a vaccine. After all, recent medical advances in the treatment of AIDS have been widely heralded as changing the prognosis for sufferers. I've been caring for HIV-infected people in London, New York and Los Angeles for almost 15 years, and treatment with triple therapy (the use of combinations of drugs to suppress AIDS) and protease inhibitors is now making many of my patients feel good and allowing them to live more rewarding, and longer, lives. Because of those advances, AIDS is no longer the No. 1 killer of Americans ages 25 to 44, according to the Centers for Disease Control and Prevention.

This is all positive news, but it is not a solution. According to UNAIDS, the new AIDS program run by the United Nations, 28-million people worldwide have HIV. Every year, 3-million more become infected. These figures represent 8,500 new cases a day. Current therapy won't combat those escalating numbers. It is potent but it is not effective in all cases, and the drugs are expensive and difficult to administer. Long-term drug therapy is available only to a privileged few who live in wealthier countries. More than 90 percent of HIV-infected people live in the developing world, far from our sophisticated medical systems.

What's more, without the oversight of highly knowledgeable physicians and without full compliance from patients _ a goal rarely achieved with therapies for other illnesses _ resistant forms of the virus are all but inevitable. While the current drugs may slow the progression of the disease in some patients, they are not a cure. If a patient stops taking the drugs, the disease rapidly re-establishes itself.

Even if we had a cure for AIDS, the epidemic would continue to wreak havoc. There are cures for syphilis and tuberculosis, yet both those diseases remain major problems the world over. Tuberculosis still kills more people every year than HIV does. To limit the spread of HIV _ or perhaps even eradicate it _ we need an inexpensive, preventive vaccine that is widely accessible to people at risk. There is an obvious precedent: The smallpox vaccine, which is cheap and easily administered, eradicated that scourge in the late 1970s.

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Developing a vaccine against HIV involves some unique obstacles. Vaccines usually work by stimulating the immune system to mimic a disease (without causing the disease itself) and then by replicating the body's natural state of immunity. That's what British physician Edward Jenner recognized 200 years ago when he observed that milkmaids who had been infected with cowpox rarely fell ill when they were subsequently exposed to the closely related smallpox virus.

No such state of immunity exists for AIDS, however; people who get infected remain infected for life. Because they don't get over AIDS and become immune, as they do with other viral diseases, creating a vaccine for AIDS is a far more difficult proposition. In fact, I used to think it was impossible until I learned that once one has been infected with one strain of HIV, one cannot be infected with a second strain, suggesting that infecting the body with the live virus can create a protective response. I believe that only a live virus may be able to do this.

The primary reason the live-attenuated vaccine has not yet been developed is fear _ fear of taking risks. In this case, it is the risk that even a weakened strain of HIV will attack the immune system of some clinical trial volunteers and possibly cause AIDS. That's a real possibility _ as it is with any other live-attenuated vaccine _ but it should not stand in the way of scientific progress.

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Vaccines aren't perfect. Sabin's oral vaccine now spares the vast majority of treated children from polio-related paralysis, but it does cause polio in about 10 children every year in the United States. Because the vaccine protects millions of children each year from the ravages of polio, the small risk is considered acceptable.

The HIV vaccine I am proposing to take may well have similar benefits and risks. Like the oral polio vaccine, it will be produced from the live virus. There is good evidence from observations in animals and people that it will work. Five years ago, Ron Desrosiers of the New England Regional Primate Research Center at Harvard Medical School published an article in the journal Science showing that a vaccine of a live-attenuated strain of simian immunodeficiency virus, the monkey equivalent of HIV, protected monkeys from catching subsequent disease-producing strains of SIV.

Critics have pointed out that several monkeys infected with attenuated SIV have become ill and argued that human volunteers will, too. But I believe that while the monkey data have been useful in predicting the potential efficacy of an AIDS vaccine, SIV is not identical to HIV, and the monkey is a different animal than a human being. To predict the vaccine's safety, we need to look at a human population.

There is promising evidence of a live vaccine's safety in humans. Two years ago, Australian investigators at the MacFarlane Burnet Center for Medical Research in Melbourne reported on eight humans who had been accidentally infected during blood transfusions more than a decade ago with an attenuated strain of HIV (a mutated strain that was missing one important gene). Not only have these individuals not succumbed to AIDS, they do not have damaged immune systems. Despite this reassuring evidence, in the five years since Desrosiers' watershed announcement, not one human study of a live-attenuated HIV vaccine has been carried out, even though the proposed live vaccine will be missing three genes, not just the one gene that the mutated virus in Australia lacks.

I feel strongly that the time has come to start working with something that has already been shown to work in monkeys and humans, albeit very few of each so far. It's time to start a clinical trial with a live-attenuated HIV vaccine in 15 to 20 clinical trial volunteers. If there are no ill effects, we should soon increase the size of the clinical trials to begin measuring the vaccine's efficacy.

The 5,500-member International Association of Physicians in AIDS Care, of which I am a member, supports this position. That's why my association colleagues and I issued a challenge in August to scientists and physicians to join us as volunteers. We have been amazed at the response. In just a few weeks, more than 50 physicians and community leaders from seven countries joined us in registering as potential volunteers. Now that number is closer to 300 _ confounding some critics who have said that we would never be able to recruit human subjects for such a study. The volunteers clearly feel that, despite the risk, if there is a chance that a live-attenuated vaccine will work and eventually save millions of lives, they will step forward to test it.

Any fears I have for my own safety are far outweighed by the knowledge that, if this study is successful, the world will be closer to having a vaccine. If the study fails and I damage my immune system, I am confident that I will be able to control the disease with the sort of therapy that I administer every day to my patients. I would be disappointed by the failure, but I don't believe it would result in my death.