Association of HIV clinical disease progression with profiles of early immune activation: results from a cluster analysis approach.
OBJECTIVE
CD4 and CD8 T-cell activation are independent predictors of AIDS. The complete activation profile of both T-cell subtypes and their predictive value for AIDS risk is largely unknown.


METHODS
A total of 564 AIDS-free women in the Women's Interagency HIV Study were followed over 6.1 years (median) after T-cell activation assessment. A cluster analysis approach was used to evaluate the concurrent activation patterns of CD4 and CD8 T cells at the beginning of follow-up in relation to AIDS progression.


METHODS
Percentages of CD4 and CD8 T cells with HLA-DR± and CD38± were assessed by flowcytometry. Eight immunologic variables (four on each CD4+ and CD8+: DR± and CD38±) were assessed to yield a 4-cluster solution on samples obtained before clinical endpoints. Proportional hazards survival regression estimated relative risks for AIDS progression by cluster membership.


RESULTS
Compared with the other three clusters, outstanding activation features of each distinct cluster of women were: Cluster 1: higher CD8(+)CD38(-)DR(-) (average=41% of total CD8 T-cell pool), CD4(+)CD38(-)DR(-) (average=53% of total CD4 T-cell pool), and CD8(+)CD38(-)DR(+) (28%); Cluster 2: higher CD8(+)CD38(+)DR(-) (44%) and CD4(+)CD38(+)DR(-) (58%); Cluster 3: higher CD8(+)CD38(+)DR(+) (49%) and CD4(+)CD38(+)DR(-) (48%); Cluster 4: higher CD8(+)CD38(+)DR(+) (49%), CD4(+)CD38(+)DR(+) (36%) and CD4(+)CD38(-)DR(+) (19%). Compared with cluster 1, women in cluster 4 had two-fold increased risk of AIDS progression (Hazard ratio=2.13; 95% confidence interval=1.30-3.50) adjusted for CD4 cell count, HIV RNA, and other confounders.


CONCLUSIONS
A profile including CD4 and CD8 T-cell activation provided insight into HIV pathogenesis indicating concurrent hyperactivation of CD4 and CD8 T cells is associated with AIDS progression.
Department of Pediatrics, Maternal, Child and Adolescent Center for Infectious Diseases and Virology, University of Southern California, Los Angeles, California, USA. rkarim@usc.edu
Roksana
R
Karim
Wendy J
WJ
Mack
Tracey
T
Stiller
Eva
E
Operskalski
Toni
T
Frederick
Alan
A
Landay
Mary A
MA
Young
Phyllis C
PC
Tien
Mike
M
Augenbraun
Howard D
HD
Strickler
Andrea
A
Kovacs
D000293:Adolescent; D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D008875:Middle Aged; D012044:Regression Analysis; D013997:Time Factors; D055815:Young Adult
D015704:CD4 Antigens; D016827:CD8 Antigens