Peter Smith has been infected with HIV since 1981 but his body has stopped it developing into AIDS.

PETER Smith will never forget the day his body declared war on HIV.

It was July 29, 1981, the day Prince Charles married Diana Spencer. As millions sat glued to the TV enjoying the illusion of a world momentarily caked in fairytale innocence, Smith lay wracked by fever in New York, his immune system fighting the virus.

Smith, who lives in rural Victoria, didn't know what he was fighting. The term AIDS was not coined until late the following year, and it took until 1985 for a virus to be identified as the culprit. No one knew that a severe flu-like illness was the sign that the immune system had suddenly woken up to the invader in its midst. Even if they had, there was nothing, then, that anybody could have done about it.

"This was 1981 - so at the time people I knew socially were getting sick (with AIDS)," Smith recalls. "They had massive weight loss; they had the night sweats, I knew a number of guys who were getting purple lesions that turned out to be Kaposi's sarcoma. I remember at the time I was riding in a cab with a friend and he clipped out this little one-paragraph news blurb in The New York Times that mentioned a 'gay cancer'. He was terrified."

Smith got better as did others, for a while, as their immune systems got the upper hand. What they didn't know was that this was the start of a decade-long running battle that the immune system would invariably lose.

But not quite invariably. Smith had an HIV test in 1985, shortly after a test first became available. It was just a precaution. He says he "wasn't very promiscuous; I didn't go to bathhouses or any of that". The results took two weeks and the test was positive.

"There was no counselling provided at that time," he says. "You were consoled, a bit. It was at that point that many people, mostly gay people of course at that time, started to die; and they were dying horrible deaths. There was no treatment, there was nothing that could be done. I was in shock."

Smith tried to look on the bright side. He checked every blotch and mole that appeared on his skin and felt a tremble of fear every time he fell ill with a cold or flu, wondering if this was the vanguard of the approaching and inevitable decline.

But the decline never came.

His CD4 count - the number of immune T-cells which HIV gradually destroys - stayed normal. And his viral load, the number of viral copies in his blood, remained so low it was undetectable on standard tests.

"I kept sort of thinking in the back of my mind that the grim reaper was just waiting there for me, and my turn would come," says Smith.

"And then about 1990, a friend of mine said: 'Do you think there's something about you that's keeping you well? And aren't people studying people like you?"'

They certainly are. Smith is an "elite controller": someone who can suppress HIV infection without the use of drugs. Despite HIV's lethality, controllers like Smith never get sick, although they never completely shake the virus either.

There are estimated to be just 2000 elite controllers in the US, equivalent to 1 in 300 people infected. They can be hard to find because they never develop AIDS. Smith, who migrated to Australia four years ago, is involved in three international studies that are trying to pin down what these people have in common.

More than 2 million people worldwide die from the virus every year, including 330,000 children. More than 33 million people are living with HIV.

For most, the virus can be held in check for many years with expensive anti-retroviral drugs. But the drugs have side-effects and once started, they cannot safely be dropped lest that creates drug resistance. They are also costly, prohibitively so for those without health insurance or who live in the developing world.

In Australia, the typical cost of anti-HIV therapy is between ＄10,000 and ＄20,000 per year per patient, although the drugs are covered by the Pharmaceutical Benefits Scheme. In the developing world, cheaper generic versions bring the cost down to ＄US150 (＄160) to ＄US200 a year, still beyond the financial reach of many of those infected.

What scientists are seeking is a vaccine that will protect people against infection, but this goal seems as elusive now as ever. One vaccine trial ended in failure last year after researchers found the inoculated group were more likely to become infected with HIV, rather than less, compared to those given a dummy injection.

Scientists are refocusing their attention on elite controllers such as Smith, trying to find what gives their immune responses the killer punch. If that could be replicated, it would be the next best thing to a vaccine.

"What's remarkable is there are people walking around for whom HIV is not a problem, who control it like other people control other infections," says Bruce Walker, professor of medicine at Harvard University and lead investigator of one of the three international studies in which Smith is enrolled.

"That to me, as a physician and a scientist, is incredibly exciting ... If you could have a vaccine that could convert people who have subsequently become infected into elite controllers, then you would see the epidemic contract."

As well as Walker's Boston study, Smith is also enrolled in a second at the US National Institutes of Health in Bethesda, Maryland and a third in Australia, run by the National Centre in HIV Epidemiology and Clinical Research at Sydney's St Vincent's Hospital. Smith visits each of the study organisers every six to 12 months to donate a fresh set of blood samples.

NCHECR's director David Cooper, the leader of the Sydney study, says while the potential remains great, the study of elite controllers has so far proved "disappointing".

"Everybody sort of thought that this would enable the breakthrough, if you could find the common factor, and as yet we haven't," Cooper says. "There may well be a common factor that we're missing; I think people are continuing to explore that. If there was something in common, you could apply it quite easily to a vaccine. The bad news ... is that the group is very heterogenous. There's not just one thing in a group of elite controllers that distinguishes them (from most HIV patients). Each of them seems to have something different about their immune response."

Cooper's study involves fewer than 20 elite controllers, and about 100 people in a broader group called long-term non-progressors who don't suppress HIV to the same degree but still take much longer to develop progressive disease than normal HIV patients.

He's looking to see whether these HIV controllers share similarities in their T-regulatory cells, which are essential for damping down the body's reaction to infection after an invader has been successfully defeated.

In Boston, Walker is trying a different tack: analysing elite controllers' chromosomes to see whether they have a genetic advantage. Armed with a ＄US20 million grant from the Gates Foundation, Walker's group is enrolling a target of 2000 elite controllers and long-term non-progressors. About half have been signed up so far.

Like Cooper, Walker is seeking more participants for his study "which is only going to be successful if we get a large number of people enrolled in it". Distance is no hurdle; blood samples can be taken by the patient's neighbourhood nurse or doctor, and shipped to Boston for analysis.

Before meeting other elite controllers Smith felt like a "scientific oddity" and "alone on the planet" as elite controllers are "viewed as outcasts" by the HIV-infected community because they do not fall ill.

Through one of the studies he came into contact with another elite controller and shared a tearful meeting with a woman who is now a good friend. "We call each other kindred spirits and brother and sister," Smith says.

"How have I survived the biggest plague of mankind since the black plague, how is it me? It was important to me to be able to identify with another human being that I had that in common with."

Useful data is starting to emerge from the studies. Last month in Banff, Canada, Walker presented findings that showed elite controllers have not simply been infected with a weedy form of HIV, as was the case with a group of people in NSW infected by contaminated blood in the 1980s. The other finding was to do with the protective effects associated with a particular gene sequence called HLA. HLA is important because it encodes a protein that shows the body's immune system that a cell is infected. Walker says a useful analogy is to think in terms of cells being machine-tool factories, which are then invaded by commandos - the virus - who force the cell's machinery to make bomb parts instead.

"HLA would be like a factory worker that works in that factory, who takes a piece of the developing bomb and hangs that out the window to show the rest of the community that something bad is happening inside the factory," Walker says.

His study has found that one type of HLA, HLA B57, is more common in people who suppress HIV effectively. Another type, HLA B35, seems more common among people who start off doing well, but whose HIV disease does later progress.

But that can't be the whole story, because Smith - whose 27 years with HIV make him one of the most successful controllers recorded - lacks HLA B57, and has the "bad" type B35, instead.

"That's part of what's confusing about this," Walker admits. "We are extremely enthusiastic about this study. We are optimistic about it, but we are also realistic. It's possible that we don't have the tools yet to answer this question."

Smith is working with his elite controller friend to set up a non-profit organisation that will provide online information for long-term non-progressors and HIV controllers and help them enrol in the research effort. "There's been so much bad news for a long time about HIV and AIDS, and very little good news," Smith says.

"Once I learned that there were all these different studies, I thought it was my duty as a human being, who cares about other people, to participate. If there's even a slight chance that I could help make a difference, this is ... the absolute least that I could do.

"I just thought it was important to have a story of hope out there."