AIDS Treatment May Renew Immune System
AIDS researchers reported for the first time Sunday that a medicinal combination containing one of the powerful new protease inhibitor drugs appears to have restored partial immune system function in people with moderately advanced HIV disease.
Because their conclusions are based on results of sophisticated tests of immune system cells in the laboratory, however, it remains uncertain whether these “reconstituted” cells actually can protect infected individuals from developing the serious and often life-threatening infections that characterize AIDS.
“We are excited and cautiously optimistic,” said Dr. Michael Lederman, an AIDS specialist at University Hospitals of Cleveland and Case Western Reserve University, which headed the research effort. “We now have a better understanding of how anti-retroviral therapy changes the body’s immune response. Now, we need to go further to see if long-term therapy can improve responses even more.”
Lederman presented his team’s findings at the Fourth Conference on Retroviruses and Opportunistic Infections, which ended Sunday. The five-day meeting was marked this year by hundreds of encouraging reports of solid, incremental advances in treating the disease and scientific understanding of how the human immunodeficiency virus works. But it lacked the drama of last year, when the first widespread studies using protease drugs brought reports of stunning clinical breakthroughs.
“It was a very good meeting, with lots of good basic science and good clinical studies,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “It clearly showed that we are going in the right direction.”
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Lederman said the results of his study showed the value of treating patients early, before their immune systems become ravaged. But he warned that the findings should be viewed prudently, and that physicians treating AIDS patients with the potent new drug “cocktails” should not discontinue additional therapies that are routinely used to stave off the onset of opportunistic infections.
Protease inhibitors, used in combination with older AIDS therapies such as the drug AZT, already have shown they can dramatically reduce levels of the AIDS virus, often to the point they are undetectable. In addition, they increase the number of immune system cells previously depleted by the virus.
But Lederman’s study is believed to be the first evidence that at least some of the new immune system cells actually will respond to an “attack” by an outside microorganism.
The work was the first field test of a new network of 16 immunology laboratories established by the allergy institute, which funded Lederman’s study.
The labs use advanced technology to study the function of various immune system cells and how they respond to exposure to different agents. In this study, for example, cells were challenged with tetanus and Candida, among other things.
Patients were treated for 12 weeks with the protease inhibitor ritonavir and two other drugs, AZT and 3TC.
Researchers said the immune system’s CD4 cells, which are the primary target of HIV, rebounded in response to the three drugs. The rebound involved both “memory” cells that had encountered HIV before and were primed to respond to it, and “naive” cells that had never been exposed to HIV.
The rebound effect also was detected with CD8 immune system cells; the boost was seen mostly in naive cells.
The news was less encouraging for V-Beta receptors, a more specific component of immune system cells whose patterns can be used to predict how the disease will progress in individuals. Skin tests and other analyses to assess immune response failed to show that V-Beta receptors returned to more normal levels, researchers said.
“The bottom line is that we need to wait to see whether the immunological reconstitution, partial though it may be, is going to turn into something clinically relevant to the patient--whether it will provide protection against the infections people with HIV ultimately get,” Fauci said. “We don’t know that yet.”
The promise of protease inhibitor drugs has been tempered this past year by recognition that they do not work for everyone.
Although many AIDS patients are feeling better and living longer, the combinations have proved less effective for those who had taken the older drugs, such as AZT, as a single-drug therapy. Unknown to researchers at the time, that approach apparently enabled the virus to develop strains resistant to the older drugs, rendering them virtually useless in combination therapy.
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Many researchers, however, express confidence that drugs even more effective than the current protease inhibitors are on the horizon.
“We created this population [patients with resistant virus] in the past because we didn’t have the tools not to, and didn’t know any better,” said AIDS specialist Robert T. Schooley, head of infectious diseases at the University of Colorado Health Sciences Center.
“Patients think they’re the failures, and they are not--we’re the failures,” Dr. Schooley said. “But we will see a different situation when more drugs become available.”
