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

Amit C Achhra; Janaki Amin; Matthew G Law; Sean Emery; Jan Gerstoft; Fred M Gordin; Michael J Vjecha; James D Neaton; David A Cooper; INSIGHT ESPRIT & SILCAAT study groups

doi:http://dx.doi.org/10.1097/QAD.0b013e32833b1b26

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

Amit C Achhra, Janaki Amin, Matthew G Law, Sean Emery, Jan Gerstoft, Fred M Gordin, Michael J Vjecha, James D Neaton, David A Cooper, INSIGHT ESPRIT & SILCAAT study groups

61 Citations (Scopus)

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.

Original language	English
Journal	AIDS
Volume	24
Issue number	12
Pages (from-to)	1877-86
Number of pages	10
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0b013e32833b1b26
Publication status	Published - 31 Jul 2010

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@article{f50e3634199945b5adda739789095278,

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

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.",

author = "Achhra, {Amit C} and Janaki Amin and Law, {Matthew G} and Sean Emery and Jan Gerstoft and Gordin, {Fred M} and Vjecha, {Michael J} and Neaton, {James D} and Cooper, {David A} and Jan Gerstoft",

year = "2010",

month = jul,

day = "31",

doi = "http://dx.doi.org/10.1097/QAD.0b013e32833b1b26",

language = "English",

volume = "24",

pages = "1877--86",

journal = "AIDS, Supplement",

issn = "1350-2840",

publisher = "Lippincott Williams & Wilkins",

number = "12",

}

TY - JOUR

T1 - Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients

AU - Achhra, Amit C

AU - Amin, Janaki

AU - Law, Matthew G

AU - Emery, Sean

AU - Gerstoft, Jan

AU - Gordin, Fred M

AU - Vjecha, Michael J

AU - Neaton, James D

AU - Cooper, David A

AU - INSIGHT ESPRIT & SILCAAT study groups

PY - 2010/7/31

Y1 - 2010/7/31

N2 - 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.

AB - 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.

U2 - http://dx.doi.org/10.1097/QAD.0b013e32833b1b26

DO - http://dx.doi.org/10.1097/QAD.0b013e32833b1b26

M3 - Journal article

SN - 1350-2840

VL - 24

SP - 1877

EP - 1886

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 12

ER -

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

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