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Immune activation and related loss of infection-fighting T cells are driven by HIV infection and not illicit drug use

Until now, it was believed that women infected with the human immunodeficiency virus (HIV) who use illicit drugs would have increased levels of immune system activation (due to chronic stimulation of antibodies in response to drugs recognized as "foreign" by the body) that leads to loss of infection-fighting CD4 T cells. However, the Women's Interagency HIV Study (WIHS) concludes that immune activation is driven by HIV infection and not illicit drug use.

This multicenter longitudinal study of the impact of HIV infection on women enrolled 2,059 HIV-positive and 569 HIV-negative women at six clinical sites in 1994 and 1995. WIHS is cosponsored by the Agency for Healthcare Research and Quality, the National Institutes of Health, and the Centers for Disease Control and Prevention.

For this WIHS study, lead author, Alan Landay, Ph.D., of Rush Medical College, and his colleagues examined levels and changes in markers of immune maturity, function, and activation in CD4 and CD8 T cells in 176 HIV-positive and 48 high-risk HIV-negative women at baseline and every 6 months over 3 years. Their goal was to investigate the relationship between HIV-1 RNA level and these immune markers and to describe the impact of other HIV-specific factors (for example, use of highly active antiretroviral therapy) and demographic and behavioral factors on these relationships.

Higher HIV-1 RNA level (greater number of virus copies per mL of blood, an indicator of more advanced disease) was strongly associated with lower CD4 and CD8 cell counts. In CD4 cells, increased activation occurred at HIV-1 RNA levels greater than 40,000 copies/mL of blood, whereas increased activation in CD8 cells occurred at much lower HIV-1 RNA levels (less than 400 copies/mL). However, drug use was not significantly associated with activation or loss of CD4 or CD 8 cells in either baseline or later analysis. There was no significant difference in CD4 activation among drug users and non-drug users or among HIV-seronegative and HIV-seropositive women.

See "Correlates of immune activation marker changes in human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women who use illicit drugs," by Dr. Landay, Lorie Benning, M.P.H., James Bremer, Ph.D., and others, in the July 15, 2003, Journal of Infectious Diseases 188, pp. 209-218.

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