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. 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⁺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 twofold 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.