HIV Study Yields Key to Treatment
A leading AIDS researcher presented new findings Sunday that appear to explain at least one reason why the human immunodeficiency virus survives the massive assault by the body’s immune system during the earliest stages of infection.
Dr. Anthony Fauci, director of the federal government’s National Institute for Allergy and Infectious Diseases, told a major AIDS conference here that preliminary research has shown that, in some people, a certain type of immune system cell can disappear within several weeks after infection, allowing the AIDS virus to escape and continue replicating.
This may help explain one of the mysteries that have nagged scientists probing the complexities of AIDS: How does HIV escape the powerful attack by the body’s immune system, which is usually successful in clearing most other viral infections?
These powerful cells, which specifically go after HIV, become depleted, giving the virus a chance to escape and infect other cells in order to reproduce.
“These cells get exhausted,” Fauci said. “After several weeks, they’re gone. You can’t find them. The virus escapes because the most potent soldier against it has disappeared.”
The finding lends further support to the growing belief among many researchers that use of powerful combinations of antiviral drugs as early as possible after infection is the most effective way to combat AIDS.
Fauci presented his research at the Third Conference on Retroviruses and Opportunistic Infections, which is considered the premier AIDS scientific forum held in the United States.
The complicated human immune system is made up of many different cells, all with specific functions. Also, immune response can vary among individuals.
Fauci said the disappearance of a type of CD8 immune system cell known as a cytotoxic T lymphocyte (CTL), or Killer T cell, does not occur in all patients but only in those who show a certain kind of immune response after infection. He said he did not know why these events occur, only that they have been observed.
In the case of the CD8 cells, Fauci’s group studied 27 patients and saw three different patterns emerge immediately after initial infection. There are many types and subsets of CD8 cells, including the killer cells.
One group experienced a major production of one subset of CD8 cells, which was the group in which the killer cells quickly became depleted, he said. This group of patients showed a more rapid progression of disease than the other two groups, he said.
A second group of patients’ immune systems responded with a moderate production of one or two different subsets of CD8 cells; while a third group showed diffuse production of several different subsets of CD8 cells, or no production at all. The third group had the best clinical outcome, he said.
In another observation, Fauci said that the killer cells seem to accumulate in the bloodstream, rather than the lymph nodes, where most of the HIV is reproducing during early infection.
“We have demonstrated that not only do these [cells] disappear rapidly, but even when they can be found, they’re not really where they’re supposed to be,” Fauci said. “Even at a time when the virus is very, very actively replicating in the lymph nodes, the CTLs--for reasons we don’t really understand--are not in the lymph nodes, but in the bloodstream.”
Ironically, killer cells are produced in the lymph nodes but are usually dispatched elsewhere to hunt for viruses, he said.
“Most viruses don’t invade the lymph nodes,” he said. “The cells are usually supposed to be traveling someplace. That’s the typical drill: Get primed in the lymph nodes, and then get the hell out of there and look for the virus.”
Following primary infection with HIV, up to 70% of infected individuals suffer an acute syndrome often characterized by flu-like symptoms. HIV replicates extensively during this period, and large quantities of the virus disseminate throughout the body, especially to the lymph nodes. This is when the body’s initial immune response occurs, and when Fauci believes treatment should probably begin.
In practice, however, this could prove difficult, because many individuals often are not aware that they have become infected, or when they became infected.
“Logistically, it will be tough,” Fauci said. “But if this initial burst of virus is responsible for driving the disappearance of these . . . cells, it makes sense to treat the virus as early as you can.”
