[30] THE THYMUS IS INVOLVED IN EARLY T-CELL REPOPULATION IN ADULT HIV-INFECTED PATIENTS UNDER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

5th International Workshop on HIV Drug Resistance & Treatment Strategies

4-8 June 2001, Scottsdale, Arizona

[TITLE:] THE THYMUS IS INVOLVED IN EARLY T-CELL REPOPULATION IN ADULT HIV-INFECTED PATIENTS UNDER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

[AUTHOR(S):] JM Franco¹, M Leal¹, A Rubio¹, M Martínez-Moya², E Ruíz-Mateos¹, J Delgado¹, A Sánchez-Quijano¹ and E Lissen¹
¹ Viral Hepatitis and AIDS study group; and ² Department of Radiology, Hospital Universitario Virgen del Rocío, Sevilla, Spain
Antivir Ther. 2001;6 Suppl 1:24

OBJECTIVE: Infection by HIV induces a profound depletion of naïve CD8 and all subsets of CD4 T-cells, which is at least partially corrected by highly active antiretroviral therapy (HAART). The redistribution and/or proliferation of mature T-cell pathways are mechanisms generally accepted. However, thymic function in adult patients remains a controversial issue. In this way, we are carrying a prospective study to determine the thymic role during T-cell repopulation.

METHODS: Sixteen consecutive antiretroviral-naïve patients starting HAART including two nucleoside analogues plus nelfinavir and/or nevirapine. They were studied at baseline and at weeks 12 and 24. Viral load levels, naïve T cell subsets (defined as CD4+CD45RA+CD45RO- and CD8+CD45RA+CD11a^low), TREC+ cells and thymic volume by computed tomography (CT) were determined at each visit. Changes in TREC+ cells were expressed as absolute count of cells/µl rather than proportion in order to discriminate increases due to reduction in TREC-negative, memory T-cells. Significant changes between variables values at different weeks were evaluated by the Wilcoxon test, and for changes during follow-up by the Friedman test.

RESULTS: Mean CD4 T cell count at baseline was 338±62 cells/µl (range, 8–804 cells/µl). After HAART, HIV-1 RNA levels became undetectable at week 24 in 12/16 patients (mean change at week 12, –2.37_log). Depleted T cell sub-populations were significantly increased during follow-up (P<0.05). As previously described, memory CD4 T-cells were significantly increased from baseline to week 12 (from 147±29 to 185±29 cells/µl, P=0.04). More interesting, an early increase at week 12 was evident in both naïve T-cells (from 95±20.4 to 157±29.7, P<0.004, in CD4 Tcells/ ml; from 91±15.5 to 142±27, P<0.039, in CD8 T-cells/µl) and thymic function, measured by absolute counts of TREC+ T-cells (from 4.70±1.54 to 6.25±1.63 cells/µl, P<0.015) and thymic volume (from 3.5±0.6 to 5.4±0.9, P<0.017). These increases were also significant at week 24 versus baseline. These changes were also evident in some patients with less than 200 CD4 T-cells/µl.

CONCLUSIONS: These results show evidences of an early thymic rebound involved in T-cell reconstitution after HAART, even in the patients who had a more advanced disease.

PRESENTING AUTHOR: JM Franco

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