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doi: 10.1097/QAD.0b013e3283601bad
Epidemiology and Social

Association of HIV clinical disease progression with profiles of early immune activation: results from a cluster analysis approach

Karim, Roksanaa,b; Mack, Wendy J.b; Stiller, Traceyc; Operskalski, Evaa; Frederick, Tonia; Landay, Aland; Young, Mary A.e; Tien, Phyllis C.f,g; Augenbraun, Mikeh; Strickler, Howard D.i; Kovacs, Andreaa

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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.

Design: 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+CD38DR (average = 41% of total CD8 T-cell pool), CD4+CD38DR (average = 53% of total CD4 T-cell pool), and CD8+CD38DR+ (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+CD38DR+ (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.

Conclusion: 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.

© 2013 Lippincott Williams & Wilkins, Inc.


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