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


CONCLUSIONS
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.
Maas
J J
JJ
The Amsterdam Cohort Study, Municipal Health Service, Department of Public Health and Environment, The Netherlands.
Gange
S J
SJ
Schuitemaker
H
H
Coutinho
R A
RA
van Leeuwen
R
R
Margolick
J B
JB
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D017252:CD3 Complex / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D015726:Giant Cells / Q000276:immunology / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics*; D006706:Homeostasis / Q000276:immunology; D018451:Homosexuality, Male; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D009426:Netherlands; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D019380:Anti-HIV Agents; D015703:Antigens, CD; D017252:CD3 Complex