T-Cell Activation Predictive of Poor Survival in Advanced Disease

A new research paper suggests that abnormal T-cell activation may be more predictive of risk of death than viral load, in patients with advanced HIV disease (CD4 cell count under 50)1; an earlier report on the same study was presented at the Retroviruses conference over a year ago.2 This study analyzed stored blood samples collected between 1986 and 1994, deliberately choosing older samples so that the results would not be confounded by the effects of modern, highly active antiretroviral therapies.

From 684 HIV-infected men in the Multicenter AIDS Cohort Study (MACS), 37 were selected as meeting the entry criteria for this study. The researchers then looked for differences between the 11 who survived less than six months, and the 26 who survived more than 18 months. They also selected a random sample of HIV-negative men from the same study, to use as a separate comparison group.

Immune activation (as measured by expression of CD38 antigen) of both CD4 and CD8 cells was strongly associated with earlier death. Naive cells were low in both those who survived and those who did not. Higher viral load was correlated with CD8 activation, but surprisingly not with CD4 activation--and after adjusting for other factors, viral load was not associated with lower survival. Also, whether or not the viruses used the CXCR4 receptor (meaning that they were SI, or syncytia-inducing viruses) did not predict survival difference in this study.


Comment

This research is important as progress toward understanding the immune-system pathogenesis of AIDS. But it may not have immediate clinical use, since the CD38 test for immune activation is not readily available. And even if the test were available, it is not clear today how doctors would use it in making treatment decisions.

References

1. Giorgi JV, Hultin LE, McKeating JA, and others. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. The Journal of Infectious Diseases. 1999; volume 179, pages 859-870.

2. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract 110].