Effect of recent thymic emigrants on progression of HIV-1 disease

Abstract

Background. The concentration of T-cell receptor-rearrangement excision DNA circles (TREC) in peripheral-blood T cells is a marker of recent thymic emigrant αβ T cells. We studied the predictive ability of measurements of TREC for clinical outcome in HIV-1-infected individuals. Methods. We measured TREC in peripheral-blood mononuclear cells with a real-time PCR assay. We studied 131 Greek participants in the Multicenter Hemophilia Cohort Study who had known HIV-1 seroconversion dates. The prognostic value of baseline TREC, CD4 T-cell count, and HIV-1 RNA concentration was assessed by Kaplan-Meier and Cox's regression analysis. Findings. Four participants had progressed to AIDS by first blood sampling. Among the remaining 127 individuals, the median value of TREC per 106 cells was 6900 (IQR 2370-15,604). Baseline TREC values were lower in the 53 who progressed to AIDS than in those who did not (geometric mean 2843 [95% CI 1468-5504] vs 6560 [4723-9113] per 106 cells

p = 0.007). The relative hazard of AIDS, adjusted for plasma viral load, CD4 T-cell count, and age at seroconversion was 1.44 (95% CI 1.04-2.01

p = 0.031) per ten-fold increase in TREC

that for death was 1.52 (1.12-2.06

p = 0.007). The adjusted relative hazards of death were 2.91 (1.91-4.44

p < 0.001) per ten-fold increase in plasma HIV-1 RNA load and 1.20 (1.04-1.38

p = 0.014) per 100-cell decrease in CD4 T-cell count. Interpretation. The concentration of TREC in the peripheral T-cell pool complements HIV-1 RNA load and CD4 T-cell count in predicting the rate of HIV-1 disease progression. Recent thymic emigrants have a role in the pathogenesis of HIV-1 disease.