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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

doi: 10.1097/QAD.0b013e3283601bad
Epidemiology and Social

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.

aDepartment of Pediatrics, Maternal, Child and Adolescent Center for Infectious Diseases and Virology

bDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles

cDepartment of Biostatistics, City of Hope National Medical Center, Duarte, California

dDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois

eDivision of Infectious Diseases, Georgetown University, Washington DC

fDepartment of Medicine, University of California San Francisco

gVeterans Affair Medical Center, San Francisco, California

hDepartment of Medicine, SUNY Downstate College of Medicine, Brooklyn

iDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.

Correspondence to Roksana Karim, 1640 Marengo Street, HRA 300, Los Angeles, CA 90033, USA. Tel: +1 323 226 2500; fax: +1 323 226 2505; e-mail:

Received 11 November, 2012

Revised 28 January, 2013

Accepted 12 February, 2013

© 2013 Lippincott Williams & Wilkins, Inc.