The Living Daylights

Some people with HIV don't get sick for years and years and years. Their lives might contain the clues for the cure.

In science, it is helpful to know what's not involved in something, as well as what is. Researchers looking into the whys of long-term survival with HIV have started to rule some things out of consideration -- things which have long been held, in the popular imagination at least, to have something to do with who got sick.

"We found no significant difference in number of sex partners, recreational drug use, or history of sexually transmitted diseases between healthy long-term positives and progressors from our cohort," the Clinic Study's researchers, including Susan Buchbinder, who heads the project, informed the 1992 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy in Anaheim.

"We have been unable to identify any lifestyle factors, such as diet, vitamin intake, sleep habit, and exercise, that set them apart from other HIV-infected persons. Nor does the number of sexual partners appear to influence outcome," UCSF's Jay Levy wrote in a paper published in 1994.

What the data does show, at least so far, is that there are three main variables in whether someone with HIV will progress to AIDS, and how rapidly that might happen: the person's genetic makeup; his or her immune response to the virus; and the strength of the virus itself.

At the Clinic Study, researchers are concentrating on the genetics of long-term survival; that is, on whether people who live healthily with HIV are genetically different than those who don't. So far, the research has identified a number of alleles, which are chromosomes on specific genes, that long-term survivors seem to have in common.

At UCSF, Levy and others are working on sorting out the immune response of long-term survivors to HIV. That research has shown that some people exposed to the virus may have successfully fought off HIV and prevented infection, and that certain kinds of T cells, called CD8+ cells, remain persistently and strongly active in long-term survivors, controlling replication of the virus. "Treatment with the CD8+ antiviral factor, once identified, could be helpful," Levy concludes. "By these approaches, long-term survival could be achieved for all HIV-infected individuals."

And there has been great interest in a New England Journal of Medicine article, published last year, that studied five Australians who were all infected with HIV by the same blood transfusion donor. They are all long-term nonprogressors, and researchers found that the HIV virus they were infected with was missing part of the gene that influences replication, presumably rendering it less virulent than other HIV viruses.

In fact, the reason behind nonprogression -- that is, the reason people can live healthily with HIV -- probably doesn't rest in one single place for every person, scientists suggest.

"The problem is now to a large extent we're flying blind," says NIAID's Schrager. "We're looking for the natural experiment to shed some light where there's darkness."

That's a dark cloud with a silver lining. There's no formula -- not yet, at least -- that will give people with HIV the ability to survive forever; on the other hand, the research into all the different reasons why some people appear to be living untouched by the virus has led to new treatments.

For example, studies of long-term nonprogressors have shown a connection between the amount of HIV virus in someone's blood and his continued health. A low viral load, as it's called, has been linked in several studies to slower or non-progression; these days, the new protease inhibitors have been shown to lower viral load in people with HIV, although whether they do so long term, as well as what effect they might have, remains to be seen.

"Why are we bothering to do this?" Schrager asks. "It's very nice to provide hope to people, and say, 'Look, there are some people who progress less than other people.' Providing hope -- that's great to do. But what we really want is a scientific clue as to what's going on."

On one of the shiny wooden tables in Kirby Maples' living room, there is a snapshot taken at Easter in the late '70s; the colors of the photograph are Kodachrome bright, greens and blues of captured grass and sunshine and two men smiling at each other, hunting for eggs. On another table, across the room, there is a bottle of opium, the letters spelled out in red on a white label. In a way, the two objects are connected, across the room and across time: Love and pain, in this epidemic, have come to stand in for each other, overlapping and overflowing, always present no matter what else is there.

"I first became aware of HIV in the early 1980s," Maples is saying. "At that time, it was very distant, something that could never happen to me." But then Maples' lover Peter, the man in the photograph on the table, fell ill, and in 1989 died of AIDS. "When I say it could never have happened to me, I mean it couldn't happen to my lover either," Maples says. "We were extensions of one another."

In 1986, Maples says, he himself tested positive. But he wasn't sick, and he didn't think much about it. "Peter got progressively worse, so while he was ill my main focus was on taking care of him. I took care of myself, too, but I didn't have any problems," Maples says. He is sitting on his huge red couch as he talks; when he moved in here a year ago, he bought new furniture, and its bright colors are like tropical flowers in the room.

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