A group of scientists led by a Johns Hopkins researcher hopes that an HIV-positive woman who has kept AIDS at bay for more than 13 years will provide clues pointing to a vaccine or new treatments for the deadly disease.
The 43-year-old patient, who was infected in 1981, appears to be suppressing the human immunodeficiency virus, said Dr. David Schwartz, whose group is funded by the National Institutes of Health and the American Foundation for AIDS Research.
In most cases, deterioration of the immune system occurs within 10 years after infection, and the loss of disease-fighting white blood cells leads to the wasting away and fatal complications that characterize AIDS.
In the current issue of the journal AIDS Research and Human Retroviruses, Dr. Schwartz's group suggests that something about the woman's immune system weakened HIV when it entered her body and is preventing her from becoming ill.
The woman has chosen to remain anonymous and is referred to only as "patient 3799."
The case is unusual because doctors have been unable to grow the virus in the laboratory from samples of her blood; more than 30 attempts have been made over the last six years at seven medical institutions, including Johns Hopkins, Stanford, Duke and the federal Centers for Disease Control and Prevention.
A further finding was that certain types of the woman's white blood cells, called lymphocytes, began to multiply when exposed to parts of the protein coat of the AIDS virus.
As the AIDS epidemic grinds into its 15th year with no vaccine or cure in sight, the woman -- and others like her who have been infected with HIV for a decade or longer without showing symptoms of AIDS -- are increasingly intriguing to researchers.
Called "long-term nonprogressors," this group of HIV-positive people may make up about 10 percent of those infected with the virus, according to scientists. Dr. Schwartz's study is one of several investigations of long-term nonprogressors being conducted nationwide.
The continued inability of scientists to grow the virus from samples of the woman's blood is highly unusual, said Dr. Schwartz, who is an assistant professor of molecular microbiology at the Hopkins School of Hygiene and Public Health.
Attempts to replicate the virus from HIV-positive blood samples are nearly always successful. But in her case, "we've done all the tricks we can think of to coax the virus out and no one has been able to," Dr. Schwartz said.
Patient 3799 first tested positive for antibodies to HIV in 1985. Doctors traced the route of transmission to a blood transfusion she had received in 1981 after having her second child.
She later had two more children. Her four children and husband are not infected with the virus.
However, her fourth child, born in November 1985, had tested positive at birth but "seroreverted" or became negative after several months. Newborns of infected mothers often test positive at birth because of maternal antibodies passed to them through the umbilical cord though less than a third are actually infected with HIV.
Exposed to virus
The transfusion received by the woman in 1981 was traced to a blood donor who was diagnosed with AIDS in 1986 and died in 1989. Two other recipients of that donor's blood also have been diagnosed with AIDS.
These facts lead Dr. Schwartz and others to suspect that patient 3799 was exposed to a viable virus, but her immune system somehow weakened it.
But they can't be sure, Dr. Schwartz added. "Because we are looking at this woman many years after she became infected, we don't know which came first -- her immune response or the weakness of the virus."
There is further evidence that the virus is present in the woman's body, he said. In addition to her consistently positive responses to HIV antibody tests, researchers found traces in her blood of proviral DNA -- genetic material from HIV.
It is possible that these traces of DNA belong to virus that is living somewhere else within the woman's body, perhaps in her lymph nodes or spleen, said Dr. Schwartz.
At this stage in the investigation, "we can't be sure what it means to find the provirus except to say that at one time there was infectious material in her body," he said.
So far, the woman has declined to have research conducted on her lymph nodes.
"I wouldn't necessarily expect to find virus there, frankly, because she has never had any swelling of her lymph nodes during this time. There's no guarantee there would be virus there," Dr. Schwartz said.
Lymphocyte activity
Additional experiments also suggest that something in the woman's immune system is suppressing the virus.
Previous research has shown that in healthy but HIV-positive people, certain white blood cells called lymphocytes are extremely active in killing immune cells infected with HIV.
In test-tube experiments using samples from patient 3799, scientists made a new discovery: This woman's lymphocytes, when exposed to parts of the protein coat of the AIDS virus, began to multiply. Some of the many experimental AIDS vaccines being tested worldwide are developed from the protein coats of HIV cells.
"This proliferative response, or cell division response . . . is very unusual to see," said Dr. Schwartz.
"For reasons we don't understand, this reaction is almost never seen among healthy noninfected people. But it is very easy to induce it in uninfected people who have been injected with experimental envelope protein vaccines for HIV."
This indicates that, in contrast to most HIV-infected patients, patient 3799's body -- even after having been infected with HIV for 13 years -- is showing responses that have only been seen among healthy individuals who were injected with experimental vaccines made from the protein coats of the AIDS virus.
The coalition of researchers led by Dr. Schwartz is continuing to investigate the genetic makeup of the virus carried by patient 3799 and is studying three other patients who also appear to be staving off the effects of HIV.
"Our plan is really to do the same studies with them as with the first person. We want to find out if there is anything intrinsically resistant about their cells, and we want to do genetic testing on the virus," he said.