Elite Controllers

BY

May 01 2010 12:00 AM ET

There is one avenue starting to create some interest for researchers around the potential for an HIV vaccine -- the ongoing studies of elite controllers, those people whose viral load remains below 50 without ever taking antiretrovirals.

In 2006, Bruce Walker, MD, of Harvard Medical School initiated the International HIV Controllers Study with the goal of identifying at least 1,000 elite controllers from around the world to uncover what mechanism in their immune system is responsible for complete viral control.

A new report on approximately 4,500 HIVers receiving care at U.S. military hospitals has indicated that 0.55% of them were elite controllers. Since there are about 1 million HIV-infected people in the United States, there should be about 5,000 elite controllers. To date, about 500 have agreed to participate in the study, and there are over 400 researchers and physicians in 200 centers around the world who are collaborating with the U.S. group.

The researchers started out by looking to see if elite controllers were simply infected with a defective virus, since HIV is a sloppy replicator and makes lots of bad copies. But the vast majority of elite controllers have a virus that replicates perfectly fine. One clue goes back to 1986, when Jay Levy, a researcher at the University of California, San Francisco, noted that HIV-infected CD4 cells don't reproduce HIV in the presence of CD8 cells (also called T-suppressor cells, or cytotoxic lymphocytes) from long-term nonprogressors. Even though this "antiviral" factor defies identification despite years of research, CD8 cells remain a primary research focus.

The Pasteur Institute has reported that HIV-specific CD8 cells from elite controllers have a unique activation marker called HLA-DR, which enables effective HIV suppression upon first contact with HIV. This bypasses the usual mechanism of infection control by CD8s that first requires CD4s to be infected, which then triggers the CD8 response. In other words, the CD 8 cells are able to attack HIV even before it finds its natural host: a CD4 cell.

Recently in the journal Immunity, the National Institute of Allergy and Infectious Diseases reported that another part of our defense system, the natural killer cells, worked better in elite controllers, destroying 68% of HIV-infected cells per hour versus 8% in people who'd with AIDS.

Then in February of this year a team from Barcelona reported that the dendritic cells in those patients who immediately control HIV secrete higher levels of an antimicrobial peptide that has potent anti-HIV activity. This may be important because dendritic cells sit on our mucous membranes and are therefore the very first cells that confront HIV after exposure.

As these studies demonstrate, there are many avenues to explore -- even using the Human Genome Project to study the DNA of elite controllers. If you are an elite controller or want more answers, visit us online at HIVPLUSmag.com.

Bowers is an HIV specialist and is board-certified in family medicine. He is in private practice in New York City. Learn more about him on his professional website.

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