Recovering From the Ravages of HIV

Scientists have found that the devastated immune systems of AIDS patients can rebound after state-of-the-art drug treatment has kept HIV at bay for a year. But the findings, reported in tomorrow's issue of Science,* make it clear that fully rebuilding an HIV-ravaged immune system is a tall order, especially given the limits of treatments available today.

New anti-HIV treatments are staving off disease and death in thousands of people. To get a better idea of how the immune system fares after therapy, immunologist Brigitte Autran of the H™pital Pitié-Salpétrire in Paris and her colleagues analyzed white blood cells, or T lymphocytes, that have a receptor known as CD4 on their surfaces. HIV selectively infects these immune system cells, leading to their destruction. In time, HIV-infected people are left with so few CD4s that their immune systems can no longer fend off even the wimpiest bacteria, viruses, or fungi.

A key benefit widely seen in people receiving potent new treatments is that CD4s dramatically rebound. Yet in all but the healthiest of infected people, CD4s do not return to normal levels. Moreover, it is unclear whether patients really regenerate CD4s or just "redistribute" ones that have been sequestered in the lymph nodes and other tissues. This, in turn, determines just how effective the "new" CD4s are at fighting infections.

The Autran group analyzed the CD4s that returned in eight adults taking a powerful combination of three anti-HIV drugs. After 1 year, the drugs had beaten back the virus and CD4 cells had jumped twofold. But because all CD4s are not created equal, the researchers used other markers on the surfaces of these cells to categorize them as either belonging to the "memory" or "naïve" subset. A memory cell only responds to an invader it has seen before, while naïve cells can launch an immune response--and create memory cells--against newcomers. During the first 4 months of treatment, the group found, returning CD4s were mostly memory cells. But after that initial phase, the naïve population rose steeply, indicating that new cells were being generated--and providing a more diverse "repertoire" of CD4s able to respond to new invaders.

The study is "the best analysis of which T cells come back after triple drug therapy that I've seen," says immunologist Donald Mosier of the Scripps Research Institute in La Jolla, California. Nevertheless, he warns, the chances are "slim to none" that anti-HIV drugs will eventually allow the immune system to restock itself completely with fully functional CD4s, both because of the limits of the drugs and of the immune system's ability to fix itself. "I'd frankly be surprised if you could continue to do this year after year," he says. Autran holds out hope, however. "I'm quite optimistic that if we could diminish the level of viral replication enough, we could approach that situation," she says.

* For more details, Science Online subscribers can link to the full text of the Report.

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