When an HIV-infected patient discontinues highly active antiretroviral therapy (HAART), the virus almost invariably rebounds to substantial levels, even if virus had become undetectable by standard tests because of therapy. New findings from the National Institute of Allergy and Infectious Diseases (NIAID), reported in the July 6, 1998, Journal of Experimental Medicine, provide an explanation.
"Latently infected, resting CD4+ cells, although relatively few in number, may be the embers that re-ignite active HIV infection if a patient stops taking combination therapy, or if the drugs become ineffective," says the paper's lead author, Tae-Wook Chun, Ph.D., of the NIAID Laboratory of Immunoregulation (LIR). "Our new data suggest that the virus rapidly rebounds because of factors present in the normal environment of the lymph nodes, particularly cytokines, which stimulate these cells to produce virus."
HAART (potent combinations of HIV drugs, generally including a protease inhibitor) can reduce the amount of virus in a person's plasma to levels that are not detectable by the most sophisticated laboratory tests. Despite the powerful effects of these drugs, however, HIV is not completely eliminated from the bodies of persons taking them. Rather, the virus persists in safe havens where the immune system cannot detect it. These hiding places include non-dividing, resting CD4+ T cells in the blood and lymph nodes, which can harbor HIV DNA for prolonged periods while remaining invisible to the immune system. In an HIV-infected person's body, 1 to 10 of every million resting CD4+ T cells contain HIV that is capable of replicating.
Many scientists think that these viral sanctuaries pose the greatest challenge to the long-term control of HIV infection in patients receiving anti-HIV therapy.
The new data from the LIR buttress this view. In a series of in vitro
experiments, Dr. Chun and his colleagues found that resting, latently infected
CD4+ cells readily
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Contact: Greg Folkers
gfolkers@nih.gov
301-496-2263
NIH/National Institute of Allergy and Infectious Diseases
6-Jul-1998