Are Some People Immune to AIDS?

By Christine Gorman

ANYONE WHO THINKS THAT BEING infected with HIV amounts to an automatic death sentence should talk to Rob Anderson. The 39-year-old San Francisco artist has beaten the odds against him by living -- no, thriving -- with the virus that causes AIDS for 14 years. At 6 ft. 2 in. and 170 lbs., Anderson has only routine medical complaints: the stuffiness of an occasional head cold or the aches and pains of a flu. His good health is not the work of some miracle drug: he has never taken AZT or any other compound to fight HIV. Incredible as it sounds, Anderson's own immune system seems to have held the villainous virus at bay. "It feels good to be on the winning side of HIV," he says. Looking to the future with surprisingly little fear, he hopes to fix up the crumbling Victorian house that he shares with his HIV-negative companion of 10 years.

Does Anderson have a natural immunity to AIDS? Just a few years ago, the idea would have seemed absurd. But that was before the results started coming in from a group of long-term health studies of 10,000 gay men, begun in the late 1970s to mid-1980s. Scientists, prodded by AIDS activists who wanted to "study the healthy" and to lift the shadows of doom that surround the disease, have now documented at least 70 cases like Anderson's. Researchers are also beginning to find similarly healthy, long-lived survivors among women and children with HIV. There is now good reason to hope that at least 5% of the estimated 1 million Americans infected with the virus may never come down with the disease.

It sounds like the most morbid of questions to ask of a patient: "Why aren't you dead yet -- or even sick?" Looking for the answers may prove to be one of the most productive avenues of research in the battle against AIDS. By shifting their focus to the healthy, many researchers believe they can make dramatic improvements in the treatment of everyone who is infected with HIV -- whether ailing or not. Just as important, their work could channel the scattershot search for a vaccine into new and more promising directions. "Early in the epidemic we thought everyone who got infected died," says Dr. Lewis Schrager of the National Institutes of Health. "And that still may be true. But I'm becoming convinced that there is something about these people who are not progressing to AIDS that is worth intensive investigation."

Resistance to HIV does not seem to be the same as more common examples of immunity. The body's protective countermeasures against measles and mumps are absolute. Years after exposure, there is no hint within the body of the foreign agents that cause those diseases. After children become immune to mumps, they can no longer infect other people.

! That is not the case for healthy HIV survivors, no matter how wholesome their glow. They test positive for antibodies to HIV and small amounts of virus can be detected in their blood. Although stable, their immune systems show telltale signs of having been weakened by the infection -- not enough to make them sick but enough to register on blood tests. "We don't know how infectious these people are," says Dr. Susan Buchbinder of the San Francisco Department of Public Health. "But we have to assume that they can pass on the virus."

So why aren't they sick? Clinicians and researchers have poked, prodded, questioned and bled their healthy human guinea pigs four to six times a year every year in search of any relevant information. Last month the NIH held its first scientific conference to evaluate the mounting evidence. So far, success in fighting HIV does not appear to be closely linked to good diets, the lack of drug use or stress or the absence of other sexually transmitted diseases. Finding no simple patterns, researchers are zeroing in on the men's individual immune responses, even searching through their genetic makeups for the reasons behind their special status. Thanks to advances that have been made in molecular biology and immunology since the start of the AIDS epidemic, scientists have found some tantalizing clues.

Their investigation begins with a white blood cell called CD4. It is the linchpin of the immune system and the main target of HIV. As a general rule, people who become infected by HIV suffer a drop in their CD4 count from a normal level of about 1,200 cells per 1/1000th of a mL of blood to 500 cells or less. The risk of developing one or more of the illnesses associated with AIDS rises dramatically if the CD4 count drops below 200.

One of the most striking things about the healthy survivors is that after the initial drop, their CD4 count stabilizes -- usually above 500. Assaulted but not overwhelmed, they no longer lose any ground against HIV. One possible explanation is that these men were exposed to a strain of the virus that is naturally weaker than most. The immune system subdues the less malevolent virus, allowing the body to fend off any new attacks by more dangerous strains. In the same way, English milkmaids who suffered from cowpox in the 18th century developed an immunity to the disease that also protected them against its more lethal cousin, smallpox. After studying these women in 1796, Edward Jenner developed his smallpox vaccine.

Investigators are also excited by the possibility that some of the HIV survivors' immune systems are cannier than a chess master. They apparently do not allow their opponent much freedom of movement and prevent the virus from mutating very often. This makes the infection easier to control because the body does not have to recognize and subdue new variations every few months. If researchers could figure out how a survivor can keep such tight control of the chessboard, then perhaps they can find a way to give other patients the same ability. Clinicians might even be able to boost the defenses of people whose immune systems have already suffered serious damage.

The healthy survivors may lead a genetically charmed life. Each of the body's cells possesses an identical inherited molecular trait, dubbed its HLA type, that allows an individual to distinguish friend from microscopic foe. Some people's HLA types are more common than others. Heredity specialists have already identified a few genetic types that appear to increase a person's chance of developing AIDS after infection. Now they are trying to determine if long-term survivors hold any inherited molecular configurations in common that could be responsible for their ability to resist HIV.

One of the most surprising findings has been the discovery of a subset of healthy, long-term survivors who have lived for years with CD4 counts less than 200. For the most part, they do not develop the secondary infections that are associated with AIDS, or if they do, they tend to recover. This only goes to prove that there is a lot about the immune system that immunologists still do not understand. Some researchers believe these men managed to press other white blood cells into service to make up for the CD4 deficiency.

Because gay men were the first people to be studied, most of the current data comes from them. In the past 18 months, however, researchers have launched a growing number of studies of women and children infected with HIV, and the preliminary results are encouraging. Once investigators start looking for healthy survivors, they find them. Still the question remains -- Why? Does the amount of virus a woman is exposed to make a difference? How effective might her vaginal and cervical tissue be as a barrier against infection? Does it matter if a child is infected while still in the womb or during passage through the birth canal?

The answers to these and other questions are just beginning to take shape. By painstakingly studying the same individuals over long periods of time, scientists are changing the way they think about AIDS. Clearly, some people can fight off the virus on their own. Over the past five years, doctors have developed more and more treatments to control the opportunistic infections and illnesses that appear in other patients. Scientists may not discover a cure, but if they learn how to control an HIV infection the way diabetes can be managed with insulin, they will have tamed one of the most feared killers of the 20th century.