Course and clinical significance of CD8+ T-cell counts in a large cohort of HIV-infected individuals

Abstract

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 ge;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.