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| |  New Insights Into Immune System Collapse Prior to AIDS BALTIMORE, MD -- Sept. 1, 1998 -- Researchers at the Johns Hopkins School of Public Health have demonstrated that a large proportion of HIV-infected individuals who develop AIDS show a rapid collapse in their T lymphocytes -- immune cells that fight viral infection in the bloodstream -- generally 18 to 30 months before the onset of clinical symptoms. The report appears in today’s issue of the Proceedings of the National Academy of Sciences. The protection provided by the two types of T lymphocytes -- CD4+ and CD8+ cells -- is one of the chief defences against viral infection. In HIV-infected individuals, the virus targets CD4+ cells for destruction, but the immune system compensates by increasing the number of CD8+ cells. This steady state, known as T-cell homeostasis, is maintained in most HIV-infected individuals for many years after becoming infected. The failure of this steady state prior to AIDS has been described in previous studies, but the identification of homeostasis and its failure had not been described at the individual level. Stephen Gange, PhD, epidemiology, Johns Hopkins School of Public Health, and colleagues developed methods for identifying the most likely time that the immune system of a given person can no longer maintain T-cell homeostasis. They then applied these methods to extensive data collected from individuals participating in the Multicenter AIDS Cohort Study (MACS), an ongoing study of over 5,000 homosexual men. Their analyses demonstrated that 77 percent of HIV-infected individuals who developed AIDS showed a dramatic decline in T lymphocytes greater than 10 percent per year. In contrast, a decline of this magnitude was seen in only 23 percent of HIV-infected men who did not go on to develop AIDS. "The data obtained in this study support the importance of the loss of T-cell homeostasis in the pathway to the severe immunodeficiency that characterises the late stages of HIV infection," Dr. Gange said. "Using the methods described in this paper, more powerful studies can now be designed to examine the occurrence of events relative to the timing of the collapse of the immune system. "This type of design will be critical to identify factors that precede the loss of T-cell homeostasis." The Multicenter AIDS Cohort Study was initiated in 1983 to study the natural history of HIV among homosexual and bisexual men in the United States and is sponsored by the National Institutes of Health.
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