CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC)

TY - JOUR

T1 - CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Therapy

T2 - The Antiretroviral Therapy Cohort Collaboration (ART-CC)

AU - Trickey, Adam

AU - May, Margaret T

AU - Schommers, Philipp

AU - Tate, Jan

AU - Ingle, Suzanne M

AU - Guest, Jodie L

AU - Gill, M John

AU - Zangerle, Robert

AU - Saag, Mike

AU - Reiss, Peter

AU - Monforte, Antonella d'Arminio

AU - Johnson, Margaret

AU - Lima, Viviane D

AU - Sterling, Tim R

AU - Cavassini, Matthias

AU - Wittkop, Linda

AU - Costagliola, Dominique

AU - Sterne, Jonathan A C

AU - Antiretroviral Therapy Cohort Collaboration (ART-CC)

AU - Boulle, Andrew

AU - Stephan, Christoph

AU - Miró, Jose M

AU - Obel, Niels

AU - Teira, Ramón

AU - Williams, Matthew

AU - Zangerle, Robert

N1 - © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

PY - 2017/9/15

Y1 - 2017/9/15

N2 - Background: We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count.Methods: We used data from 13 European and North American cohorts of human immunodeficiency virus-infected, antiretroviral therapy (ART)-naive adults who started ART during 1996-2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0-0.40, 0.41-0.64 [reference], >0.64) and CD8 count (0-760, 761-1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines.Results: During 276526 person-years, 1834 of 49865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00-1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01-1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality.Conclusions: In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.

AB - Background: We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count.Methods: We used data from 13 European and North American cohorts of human immunodeficiency virus-infected, antiretroviral therapy (ART)-naive adults who started ART during 1996-2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0-0.40, 0.41-0.64 [reference], >0.64) and CD8 count (0-760, 761-1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines.Results: During 276526 person-years, 1834 of 49865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00-1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01-1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality.Conclusions: In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.

KW - Adolescent

KW - Adult

KW - Aged

KW - Anti-HIV Agents/therapeutic use

KW - Biomarkers/blood

KW - CD4-CD8 Ratio

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Cause of Death

KW - Europe/epidemiology

KW - Female

KW - HIV Infections/drug therapy

KW - Humans

KW - Lymphocyte Count

KW - Male

KW - Middle Aged

KW - North America/epidemiology

KW - Prognosis

KW - Proportional Hazards Models

KW - Viral Load

KW - Young Adult

U2 - 10.1093/cid/cix466

DO - 10.1093/cid/cix466

M3 - Journal article

C2 - 28903507

SN - 1058-4838

VL - 65

SP - 959

EP - 966

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 6

ER -