Association of HIV clinical disease progression with profiles of early immune activation

Results from a cluster analysis approach

Roksana Karim, Wendy J. Mack, Tracey Stiller, Eva Operskalski, Toni Frederick, Alan Landay, Mary A. Young, Phyllis C. Tien, Mike Augenbraun, Howard Strickler, Andrea Kovacs

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1473-1481
Number of pages9
JournalAIDS
Volume27
Issue number9
DOIs
StatePublished - Jun 1 2013

Fingerprint

Cluster Analysis
Disease Progression
HIV
T-Lymphocytes
Acquired Immunodeficiency Syndrome
HLA-DR Antigens
CD4 Lymphocyte Count
RNA
Confidence Intervals
Survival

Keywords

  • AIDS
  • Cluster Analysis
  • Immune activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Karim, R., Mack, W. J., Stiller, T., Operskalski, E., Frederick, T., Landay, A., ... Kovacs, A. (2013). Association of HIV clinical disease progression with profiles of early immune activation: Results from a cluster analysis approach. AIDS, 27(9), 1473-1481. https://doi.org/10.1097/QAD.0b013e3283601bad

Association of HIV clinical disease progression with profiles of early immune activation : Results from a cluster analysis approach. / Karim, Roksana; Mack, Wendy J.; Stiller, Tracey; Operskalski, Eva; Frederick, Toni; Landay, Alan; Young, Mary A.; Tien, Phyllis C.; Augenbraun, Mike; Strickler, Howard; Kovacs, Andrea.

In: AIDS, Vol. 27, No. 9, 01.06.2013, p. 1473-1481.

Research output: Contribution to journalArticle

Karim, R, Mack, WJ, Stiller, T, Operskalski, E, Frederick, T, Landay, A, Young, MA, Tien, PC, Augenbraun, M, Strickler, H & Kovacs, A 2013, 'Association of HIV clinical disease progression with profiles of early immune activation: Results from a cluster analysis approach', AIDS, vol. 27, no. 9, pp. 1473-1481. https://doi.org/10.1097/QAD.0b013e3283601bad
Karim, Roksana ; Mack, Wendy J. ; Stiller, Tracey ; Operskalski, Eva ; Frederick, Toni ; Landay, Alan ; Young, Mary A. ; Tien, Phyllis C. ; Augenbraun, Mike ; Strickler, Howard ; Kovacs, Andrea. / Association of HIV clinical disease progression with profiles of early immune activation : Results from a cluster analysis approach. In: AIDS. 2013 ; Vol. 27, No. 9. pp. 1473-1481.
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abstract = "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.",
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AU - Frederick, Toni

AU - Landay, Alan

AU - Young, Mary A.

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N2 - 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.

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