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

摘要

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.