"Without HAART, we found that interleukin-6, tumor necrosis factor-alpha and interleukin-2, signalling molecules which are normally found in copious amounts in a person's lymph nodes, readily induced HIV replication in latently infected, resting CD4+ T cells," says Dr. Chun. "Our in vitro findings help explain the well-documented phenomenon of viral rebound seen in virtually all patients with no easily detectable virus in their blood as a result of HAART who discontinue therapy."
The researchers found that the cytokine combination activated purified resting CD4+ T cells from both HIV-infected patients receiving HAART, and from HIV-infected patients who had never taken HAART. Previous studies had shown that the three cytokines could independently induce HIV replication in cell lines, and in certain cells from the bloodstream. Before this study, however, the effects of the cytokines on latently infected, resting CD4+ T cells were unclear.
The new data suggest possible approaches to "purging" the body of cells latently infected with HIV.
"We now know that it is possible to drive latently infected CD4+ cells, at least in vitro, to a state of productive infection by using combinations of cytokines and/or antibodies to the CD3 molecule on the cell surface," says Anthony S. Fauci, M.D., NIAID director, LIR chief and senior author on the paper. "Thus, one approach to purging these cells might be to stimulate them to spit out virus under the cover of HAART. Two assumptions are built into this scenario: cells activated to produce virus will die, and HAART will prevent the spread of released virus.
"Our group and others are pursuing further laboratory studies as well as clinical trials with HIV-infected patients to determine if such an approach is feasible."
Co-authors of
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Contact: Greg Folkers
gfolkers@nih.gov
301-496-2263
NIH/National Institute of Allergy and Infectious Diseases
6-Jul-1998