Within the Danish HIV cohort study, 3,882 HIV-infected individuals who received care in Copenhagen during 1995-2012, where assessed for CD8 + T-cell counts. The objective was to examine trajectories of CD8 + T-cell counts before and after combination antiretroviral therapy and associations with mortality. Reference values for CD8 + T-cell counts were obtained from 1,230 persons from the background population. Mortality rate ratios were estimated by Poisson regression.

CD8 + T-cell counts were elevated during untreated HIV infection and remained elevated through 10 years of combination antiretroviral therapy. A slight drop of 130 cells/μL (interquartile range, -160 to 410 cells/μL) in the median CD8 + T-cell count was observed after antiretroviral therapy 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 combination antiretroviral therapy initiation were associated with a poor increase in the CD4 + T-cell count (relative risk, 2.22; 95% confidence interval, 1.42-3.48). Individuals with a CD8 + T-cell count of <500 cells/μL 1 year after antiretroviral therapy 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 antiretroviral therapy for 10 years, a CD8 + T-cell count of >1,500 cells/μL was associated with increased non-AIDS-related mortality (mortality rate ratio, 1.82; 95% CI, 1.09-3.22), compared with a CD8 + T-cell count of 500-1,500 cells/μL.

In conclusion, CD8 + T-cell counts are elevated during HIV infection and do not normalize despite long-term antiretroviral therapy. Low CD8 + T-cell counts are associated with increased AIDS-related mortality. Marked elevations in CD8 + T-cell counts after long-term antiretroviral therapy are associated with increased non-AIDS-related mortality.