----------------------------------------------------------------- HIV Survivor Could Provide Clues to Assist in AIDS Battle ----------------------------------------------------------------- By Marc Kusinitz Scientists at Hopkins and elsewhere have discovered important clues that may explain the remarkable ability of a woman infected with HIV-1 to suppress growth of the virus or the emergence of AIDS for many years. The clues emerged from studies of a woman infected with HIV-1 for 13 years but with little trace of the virus within her. She has never developed AIDS-related diseases. The research group is now studying four other HIV-infected long-term survivors who also seem to have suppressed reproduction of HIV-1. "There are at least a handful of long-term survivors infected with HIV who have never had symptoms and whose immune systems appear to have suppressed the AIDS virus to the point where it cannot be grown from the blood in the laboratory setting, even when we use the best tricks we have for growing and detecting HIV," said David Schwartz, assistant professor of molecular microbiology and immunology at the School of Hygiene and Public Health. "This knowledge could lead to development of improved AIDS vaccines and therapies," Dr. Schwartz said. Dr. Schwartz is the leader of the study, funded by the National Institutes of Health and the American Foundation for AIDS Research. While there is a previous report of an infected donor and several recipients of HIV-tainted clotting factor doing very well years after infection, the present case differs in several key respects, including the fact that the blood donor and two other recipients have died of AIDS. The patient's children, breast-fed for one year after her infection, and her husband remain negative for HIV, according to the report, published in the December issue of AIDS Research and Human Retroviruses. The woman, referred to as patient 3799, was infected by a contaminated blood transfusion during childbirth in 1981, but has never had HIV-associated diseases. Although her levels of CD4 T cells, an important type of immune system cell, have been reduced since they were first measured in 1988, they have held steady over that period. "Since she was first studied in 1985, laboratory tests have consistently shown that her immune system has been making antibodies to HIV-1," Dr. Schwartz said. "This is strong evidence that she is infected with the virus. Test-tube experiments showed a lower number of antibody-producing cells making antibodies against HIV-1 compared to most other HIV-positive individuals." Nevertheless, in more than 30 separate attempts over the past six years, researchers at Hopkins and other laboratories around the country have never succeeded in isolating replicating HIV from the patient's blood or bone marrow, despite using the most sensitive and sophisticated methods available. They have detected very small amounts of proviral DNA--genetic material belonging to HIV-1--in her blood T cells. Because HIV-1 DNA gets into human genes inside infected cells, researchers say it is possible the HIV-1 DNA they found actually belongs to multiplying viruses living somewhere other than the circulating blood (for example, lymph nodes, spleen or thymus). Or it may belong only to "dead end" mutant viruses that got into the DNA of those white blood cells and then were copied along with the cells' own DNA during normal cell division. However, the Hopkins-led team reported clues that suggest how the woman's immune system was able to suppress HIV-1 replication. First, the researchers found that certain cells, called lymphocytes, were very active in killing immune system cells infected with HIV-1. This is common among symptom-free HIV-positive individuals, Dr. Schwartz said. Unusual, however, was that, in test-tube experiments, the woman's lymphocytes multiplied when exposed to parts of the protein coat of the AIDS virus. For reasons not well understood, such proliferation is almost never seen among infected people, even early in disease or during long symptom-free intervals. The authors suggest that the patient may have been able to suppress all the AIDS viruses that infected her, as well as those that developed through mutation since then. Only defective, slow-growing viruses would have remained in her white cells, occasionally making individual pieces of the virus. These pieces of virus could then have stimulated the woman's immune system even though they weren't full, active viruses. The reason that the level of CD4 cells is reduced, but stable, might be due to indirect consequences of the immune response to those pieces of viral protein. For example, the viral pieces might have somehow caused the cells to self-destruct, stick together and die, or become "innocent by-standers" when the immune system attacked other infected white blood cells.
Go to Gazette Homepage