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

Achhra, AC; Amin, J; Law, MG; Emery, S; Gerstoft, J; Gordin, FM; Vjecha, MJ; ... INSIGHT ESPRIT & SILCAAT study groups, ; + view all (2010) Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS , 24 (12) pp. 1877-1886. 10.1097/QAD.0b013e32833b1b26.

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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/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.

Type: Article
Title: Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients.
Location: England
DOI: 10.1097/QAD.0b013e32833b1b26
Keywords: Adult, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Disease Progression, Endpoint Determination, Female, HIV Infections, HIV-1, Humans, Immunologic Deficiency Syndromes, Male, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
URI: http://discovery.ucl.ac.uk/id/eprint/1399482
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