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

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• 作者：Hatzakis ; Angelos ; Touloumi ; Giota ; Karanicolas ; Rose ; Karafoulidou ; Anastasia ; Mandalaki ; Titika ; et. al.
• 刊名：The Lancet
• 出版年：2000
• 出版时间：February 19, 2000
• 年：2000
• 卷：355
• 期：9204
• 页码：599-604
• 全文大小：131 K

文摘

Summary

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=0·017). 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.