Scientists at Jefferson Medical College of Thomas Jefferson University in Philadelphia have coined the term "immune reconstitution syndrome" to describe a medical paradox. Writing in the Sept. 19 issue of the Annals of Internal Medicine, they describe a condition, seen recently in some AIDS patients taking a powerful cocktail of anti-HIV medicines, that has begun turning up in those whose immune systems actually regain some strength and vigor from the therapy. For unexplained reasons, the doctors say, some patients come under attack from opportunistic infections that ordinarily should not be much of a bother.
The researchers suggest that the syndrome, which in some cases has been fatal, results from a newly strengthened immune system's inflammatory reaction to bacteria or viruses already present in the treated HIV patient.
More than a year ago, the researchers began to see patients with HIV, the virus that causes AIDS, develop infections at times they weren't expecting. These patients were responding to highly active antiretroviral therapy, or HAART, and were improving.
"Ideally, opportunistic infections should not occur," says Joseph DeSimone, M.D., who is an instructor in the Department of Medicine at Jefferson Medical College. "When we see someone who is ill, we 'risk-stratify' him or her based on his immune system status. For an HIV-positive patient with a poor immune system and a fever, there is a laundry list of infections potentially causing it. When we see someone with restored immunity who is taking antiretroviral drugs, the list is shorter. This new syndrome was surprising."
The doctors saw some patients with mycobacterium avium infections, a typical infection in HIV patients. But what was unusual was the timing. "The infection was not showing up in someone with end-stage AIDS who wasn't taking anti-retrovirals and HAART, but in someone getting better and on HAART," Dr. DeSimone says.
The Jefferson doctors decided to search the medical literature and began asking colleagues if they too had seen similar situations with some AIDS patients. "Other physicians at other hospitals began reporting infections such as CMV retinitis," says Timothy Babinchak, M.D., clinical director of the division of infectious disease at Thomas Jefferson University Hospital and clinical associate professor of medicine at Jefferson Medical College. "The AIDS-related blindness some patients experience was getting better and when patients were started on their HAART therapy they overall were getting better. But then they seemed to be getting an aggravation of their disease. It was another process, not necessarily the CMV being reactivated. It was an inflammatory reaction to the CMV infection already there.
"All of these findings coming together were the nexus for an immune reconstitution disease syndrome," he explains. "Here were patients who didn't have enough of an inflammatory disease response necessarily because of their underlying HIV [and their weakened immune systems], but had these infections. Once we restored the immune system, getting their viral load down and the CD4 immune cell count up, they could mount inflammatory reactions. Inflammatory responses were what we were seeing as illness in people who hadn't necessarily had that illness before - as in the case of mycobacterium, or in those who had recovered, as in the case of CMV retinitis."
"We think that patients probably have already been infected with one of these pathogens before their HAART treatment," explains Roger J. Pomerantz, M.D., professor of medicine, biochemistry and molecular pharmacology, and chief of the division of infectious diseases at Jefferson Medical College. "There's no immune system initially to cause any inflammatory reaction and tissue destruction in untreated patients with AIDS. When the system comes back, the immune reaction occurs," says Dr. Pomerantz, who also directs Jefferson's Center for Human Virology.
Dr. Pomerantz notes that physicians need to be aware of this syndrome, which at times may be difficult to diagnose.
One patient, for example, had back pain which at first was thought to be a spinal tumor. Doctors subsequently found an inflammatory mass next to the spine.
Dr. DeSimone says that some physicians give antibiotics to treat the particular illness. In other cases, anti-inflammatory drugs may be prescribed. Some doctors reduce the HAART treatment. "No one is exactly sure what to do against this syndrome yet," he says.
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Journal
Annals of Internal Medicine