Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients

Achhra, Amit C., Amin, Janaki, Law, Matthew G., Emery, Sean, Gerstoft, Jan, Gordin, Fred M., Vjecha, Michael J., Neaton, James D. and Cooper, David A. (2010) Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS, 24 12: 1877-1886. doi:10.1097/QAD.0b013e32833b1b26


Author Achhra, Amit C.
Amin, Janaki
Law, Matthew G.
Emery, Sean
Gerstoft, Jan
Gordin, Fred M.
Vjecha, Michael J.
Neaton, James D.
Cooper, David A.
Title Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients
Journal name AIDS   Check publisher's open access policy
ISSN 0269-9370
1473-5571
Publication date 2010-07-31
Sub-type Article (original research)
DOI 10.1097/QAD.0b013e32833b1b26
Open Access Status Not yet assessed
Volume 24
Issue 12
Start page 1877
End page 1886
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Objective: To investigate the relative predictive value of CD4+ metrics for serious clinical endpoints.

Design: Observational.

Methods: Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4+ metrics (latest, baseline and nadir CD4+ cell count, latest CD4+%, time spent with CD4+ count below certain thresholds and CD4+ slopes) independently predictive of all-cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4+ cell count.

Results: Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1-8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4+ cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4+ slope over seven visits, after additional adjustment for latest CD4+ cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope <-10 cells/μl per month vs. 0 ± 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/μl per month vs. 0 ± 10: 2.62, 95% CI 1.62-4.22). Latest CD4+ cell count (per log2 rise) was the best predictor across all four endpoints and predicted hepatic (hazard ratio 0.46, 95% CI 0.33-0.63) and renal events (hazard ratio 0.39, 95% CI 0.21-0.70), but not cardiovascular events (hazard ratio 1.05, 95% CI 0.77-1.43) or non-AIDS cancers (hazard ratio 0.78, 95% CI 0.59-1.03).

Conclusion: Latest CD4+ cell count is the best predictor of serious endpoints. CD4+ slope independently predicts all-cause and non-AIDS deaths.
Keyword AIDS
CD4+
CD4+ cell counts
Immunodeficiency
Serious non-AIDS events
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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