Strong association between failure of T cell homeostasis and the syncytium-inducing phenotype among HIV-1-infected men in the Amsterdam Cohort Study

Abstract

Objective: To assess the association between T cell homeostasis and its failure and 1.) the occurrence of AIDS and 2.) the switch from the non-syncytium-inducing (NSI) to the syncytium-inducing (SI) HIV virus phenotype.

Methods: For each of 325 homosexual men in the Amsterdam Cohort Study, the slope of the CD3 T cell count versus time was determined. The timing (T cell inflection point (IP)) and magnitude of the change in slope were correlated with the time of the NSI/SI switch.

Results: Median T cell slopes before the IP (pre-IP) were nearly zero regardless of whether AIDS occurred; the slopes after the IP (post-IP) were associated with clinical outcomes, with a median annual decline of 17.6% among those who developed AIDS and increase of 4.6% in those remaining AIDS free. Among subjects considered to have a true IP (decline > 8.2%/year post-IP), the times of the SI switch and the IP slope were highly correlated (r = 0.65); among those with AIDS, the SI switch preceded the IP by a median of 0.63 years.

Conclusion: These results support the concept of blind T cell homeostasis and also suggest that HIV-1 SI variants play an important role in the failure of T cell homeostasis.