Document Detail


Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients.
MedLine Citation:
PMID:  20588170     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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/microl per month vs. 0 +/- 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 2.62, 95% CI 1.62-4.22). Latest CD4(+) cell count (per log(2) 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.
Authors:
Amit C Achhra; Janaki Amin; Matthew G Law; Sean Emery; Jan Gerstoft; Fred M Gordin; Michael J Vjecha; James D Neaton; David A Cooper;
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  24     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-12     Completed Date:  2011-05-06     Revised Date:  2011-08-02    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  1877-86     Citation Subset:  IM; X    
Affiliation:
National Centre in HIV Epidemiology and Clinical Research, Faculty of Medicine, University of New South Wales, Cliffbrook Campus, Coogee, Sydney, New South Wales, Australia. aachhra@nchecr.unsw.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adult
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes / immunology*
Disease Progression
Endpoint Determination
Female
HIV Infections / drug therapy,  immunology*,  mortality
HIV-1 / immunology*
Humans
Immunologic Deficiency Syndromes / drug therapy,  immunology*,  mortality
Male
Predictive Value of Tests
Proportional Hazards Models
Prospective Studies
Grant Support
ID/Acronym/Agency:
U01 AI046957-01/AI/NIAID NIH HHS; U01 AI046957-02/AI/NIAID NIH HHS; U01 AI046957-03/AI/NIAID NIH HHS; U01 AI046957-04/AI/NIAID NIH HHS; U01 AI046957-05/AI/NIAID NIH HHS; U01 AI046957-05S1/AI/NIAID NIH HHS; U01 AI046957-05S2/AI/NIAID NIH HHS; U01 AI046957-05S3/AI/NIAID NIH HHS; U01 AI068641/AI/NIAID NIH HHS; U01 AI068641-01/AI/NIAID NIH HHS; U01 AI068641-01S1/AI/NIAID NIH HHS; U01 AI068641-02/AI/NIAID NIH HHS; U01 AI068641-02S1/AI/NIAID NIH HHS; U01 AI068641-03/AI/NIAID NIH HHS; U01 AI068641-04/AI/NIAID NIH HHS; U01 AI068641-04S1/AI/NIAID NIH HHS; U01 AI068641-05/AI/NIAID NIH HHS; U01 AI46957/AI/NIAID NIH HHS
Investigator
Investigator/Affiliation:
James D Neaton / ; D Abrams / ; A Babiker / ; J Baxter / ; David A Cooper / ; C J Cohen / ; D Cohn / ; J H Darbyshire / ; W El-Sadr / ; Sean Emery / ; Fred M Gordin / ; H C Lane / ; G Larson / ; M H Losso / ; J D Lundgren / ; J Nadler / ; A N Phillips / ; Y Lévy / ; D Abrams / ; A Babiker / ; P Cahn / ; B Clotet / ; N Clumeck / ; David A Cooper / ; J H Darbyshire / ; Sean Emery / ; U Hengge / ; H C Lane / ; J Lange / ; G Levi / ; J D Lundgren / ; R Mitsuyasu / ; James D Neaton / ; J P Routy / ; G Tambussi /
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