Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients.
OBJECTIVE
To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints.


METHODS
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).


CONCLUSIONS
Latest CD4(+) cell count is the best predictor of serious endpoints. CD4(+) slope independently predicts all-cause and non-AIDS deaths.
Achhra
Amit C
AC
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
Amin
Janaki
J
Law
Matthew G
MG
Emery
Sean
S
Gerstoft
Jan
J
Gordin
Fred M
FM
Vjecha
Michael J
MJ
Neaton
James D
JD
Cooper
David A
DA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies