TY - JOUR

T1 - Course and Clinical Significance of CD8+ T-Cell Counts in a Large Cohort of HIV-Infected Individuals

AU - Helleberg, Marie

AU - Kronborg, Gitte

AU - Ullum, Henrik

AU - Ryder, Lars P

AU - Obel, Niels

AU - Gerstoft, Jan

N1 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - OBJECTIVES: To examine trajectories of CD8(+) T-cell counts before and after combination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected individuals and associations with mortality.METHODS: CD8(+) T-cell counts were measured in 3882 HIV-infected individuals who received care in Copenhagen during 1995-2012. Reference values were obtained from 1230 persons from the background population. Mortality rate ratios were estimated by Poisson regression.RESULTS: CD8(+) T-cell counts were elevated during untreated HIV infection and remained elevated through 10 years of cART. A slight drop of 130 cells/µL (interquartile range, -160 to 410 cells/μL) in the median CD8(+) T-cell count was observed after cART initiation. CD8(+) T-cell counts stabilized at approximately 900 cells/µL (95th percentile of the background population, 835 cells/µL). Markedly elevated CD8(+) T-cell counts at cART initiation were associated with a poor increase in the CD4(+) T-cell count (relative risk, 2.22; 95% confidence interval [CI], 1.42-3.48). Individuals with a CD8(+) T-cell count of <500 cells/µL 1 year after cART initiation had an increased mortality rate (mortality rate ratio, 1.73; 95% CI, 1.29-2.32) and a higher proportion of deaths attributable to AIDS-related conditions, compared with individuals with CD8(+) T-cell counts of ≥500 cells/µL. After receiving cART for 10 years, a CD8(+) T-cell count of >1500 cells/µL was associated with increased non-AIDS-related mortality (mortality rate ratio, 1.82; 95% CI, 1.09-3.22), compared with a CD4(+) T-cell count of 500-1500 cells/µL.CONCLUSIONS: CD8(+) T-cell counts are elevated during HIV infection and do not normalize despite long-term cART. Low CD8(+) T-cell counts are associated with increased AIDS-related mortality. Marked elevations in CD8(+) T-cell counts after long-term cART are associated with increased non-AIDS-related mortality.

AB - OBJECTIVES: To examine trajectories of CD8(+) T-cell counts before and after combination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected individuals and associations with mortality.METHODS: CD8(+) T-cell counts were measured in 3882 HIV-infected individuals who received care in Copenhagen during 1995-2012. Reference values were obtained from 1230 persons from the background population. Mortality rate ratios were estimated by Poisson regression.RESULTS: CD8(+) T-cell counts were elevated during untreated HIV infection and remained elevated through 10 years of cART. A slight drop of 130 cells/µL (interquartile range, -160 to 410 cells/μL) in the median CD8(+) T-cell count was observed after cART initiation. CD8(+) T-cell counts stabilized at approximately 900 cells/µL (95th percentile of the background population, 835 cells/µL). Markedly elevated CD8(+) T-cell counts at cART initiation were associated with a poor increase in the CD4(+) T-cell count (relative risk, 2.22; 95% confidence interval [CI], 1.42-3.48). Individuals with a CD8(+) T-cell count of <500 cells/µL 1 year after cART initiation had an increased mortality rate (mortality rate ratio, 1.73; 95% CI, 1.29-2.32) and a higher proportion of deaths attributable to AIDS-related conditions, compared with individuals with CD8(+) T-cell counts of ≥500 cells/µL. After receiving cART for 10 years, a CD8(+) T-cell count of >1500 cells/µL was associated with increased non-AIDS-related mortality (mortality rate ratio, 1.82; 95% CI, 1.09-3.22), compared with a CD4(+) T-cell count of 500-1500 cells/µL.CONCLUSIONS: CD8(+) T-cell counts are elevated during HIV infection and do not normalize despite long-term cART. Low CD8(+) T-cell counts are associated with increased AIDS-related mortality. Marked elevations in CD8(+) T-cell counts after long-term cART are associated with increased non-AIDS-related mortality.

KW - Adult

KW - Anti-Retroviral Agents

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Denmark

KW - Female

KW - HIV Infections

KW - Humans

KW - Male

KW - Middle Aged

U2 - 10.1093/infdis/jiu669

DO - 10.1093/infdis/jiu669

M3 - Journal article

C2 - 25489001

VL - 211

SP - 1726

EP - 1734

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 11

ER -