807-W. TREC Response to Antiretroviral Therapy in HIV-Infected Children in the PENTA 5 Trial

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Session 105 Poster Session
Pediatric HIV Infection: Disease Progression and Responses to Therapy
Session Time: 4:30-6:30 pm
Room 4E-F

807-W.

TREC Response to Antiretroviral Therapy in HIV-Infected Children in the PENTA 5 Trial
A. de Rossi¹, N. Klein*², D. De Forni¹, A. Babiker³, A. S. Walker³, and D. M. Gibb³ for the PENTA Imunology Committee
¹Padova, Italy; ²Inst. of Child Hlth. London, UK; and ³MRC Clin. Trials Unit London, UK

Background: In children, increases in CD4 following antiretroviral therapy (ART) are mainly due to CD45RA+ cells. To investigate the thymus contribution, we measured T-cell receptor gene rearrangement excision circles (TREC), and CD45 isotypes following ART in previously untreated HIV-infected children.
Methods: 128 children (median 5.3 years (0.3-16.7)) were randomised to ZDV+3TC or ZDV+ABC or 3TC+ABC. Asymptomatic children (n=55) were also randomised to NFV/placebo; symptomatic children all received NFV (n=73). TRECs were measured in PBMC and CD4 cells in a subset of 33 children at 0, 4, 12, 24, and 48 weeks. CD45RA+ and RO+ were measured by flow cytometry in 17 of the 33 children.
Results: The mean increase in log₁₀ TREC at week 24 was 0.28 log₁₀ per 100,000 PBMC (95% CI 0.12-0.45, p=0.001). Similar increases in log₁₀ TREC were observed in CD4 cells but appeared earlier than in PBMC cells. CD45 RO+ and RA+ increased by 2.0% and 11.8% respectively at week 48 (p<0.001). Although absolute log₁₀ TREC levels were related to age, changes in log₁₀ TREC were independent of age. The strongest predictor of change in log₁₀ TREC was change in CD4% (eg 5% greater increase in CD4% was associated with a 0.08 greater increase in log₁₀ TREC (95% CI 0.03-0.13, p=0.0008)), but higher baseline CD4% was associated with a smaller increase in TREC. HIV RNA <50 copies/mL was the best virological predictor of change in TREC, associated with a 0.16 smaller increase in log₁₀ TREC (95% CI 0.04-0.27, p=0.007). After adjusting for change in total CD4% and RNA<50, there was marginal evidence for an additional effect of change in CD4 RO% (p=0.08), but numbers were small.
Conclusions: Initiation of ART is associated with significant increases in TREC and correlates with change in CD4%, but not with age. These results suggest that thymically derived cells play a significant role in peripheral CD4 cell repopulation in children.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections