502-M. Immune Reconstitution in HIV-Infected Children following Antiretroviral Therapy

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Session 69 Poster Session
Immunopathogenesis Issues Addressed by Therapeutic Interventions
Session Time: 4:30-6:30 pm
Room 4E-F

502-M.

Immune Reconstitution in HIV-Infected Children following Antiretroviral Therapy
V. Haridas*, A. Chandrasekaran, S. Chavan, and S. Pahwa
North Shore-Long Island Jewish Res. Inst. Immunology Ctr., Manhasset, NY

Background: Immune reconstitution following antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients may result from recovery of thymic function, peripheral redistribution, or decreased T-cell destruction. In the present study we have investigated thymic function by estimating the levels of T-cell receptor excision circles (TRECs). In addition to this, activation and naďve status of T cells were studied to investigate their role in immune reconstitution.
Methods: This study consists of 21 HIV-infected patients (age range 0.2 - 19.2 years, median 9 years) who are on antiretroviral treatment for >24 months. TRECs were estimated by TaqMan real-time multiplex PCR assay. Surface markers for naďve and activated phenotype were studied by multi-color flow cytometry. The correlation between different parameters was analyzed by Spearman Rank Correlation analysis.
Results: In this study we found that there was a significant positive correlation between TREC levels and absolute CD4 numbers (r= 0.7, p<0.001), and the CD4/CD8 ratio (r=0.42, p=0.03). These parameters showed a negative correlation with viral load [CD4 abs (r= -0.56, p=0.02), CD4/CD8 ratio (r= -0.7, p<0.001)]. The level of T cell apoptosis marker CD95 and the level of memory CD4 population negatively correlated with TREC (r= -0.42, p=0.04 and r= -0.55, p=0.004 respectively) while CD4⁺CD45RA⁺62L⁺ levels positively correlated with TREC levels (r= 0.55, p=0.004). Plasma virus load negatively correlated with %CD8⁺CD28⁺ (r= -0.77, p<0.001) and positively correlated with %CD8⁺CD38⁺HLA-DR⁺ (r= 0.8, p<0.001).
Conclusion: The results of this study suggest that peripheral T-cell reconstitution is a cumulative effect of active thymic output and decreased activation status of peripheral T-cells which thereby decreases peripheral T-cell destruction following effective viral suppression.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections