Immune reconstitution in HIV-1-infected children on antiretroviral therapy: role of thymic output and viral fitness
Articolo
Data di Pubblicazione:
2002
Citazione:
Immune reconstitution in HIV-1-infected children on antiretroviral therapy: role of thymic output and viral fitness / L. Ometto, D. De Forni, F. Patiri, V. Trouplin, F. Mammano, V. Giacomet, C. Giaquinto, D. Douek, R. Koup, A. De Rossi. - In: AIDS. - ISSN 0269-9370. - 16:6(2002), pp. 839-849.
Abstract:
Objective To investigate the role of thymic output and viral fitness in immune reconstitution in HIV-1-infected children on antiretroviral therapy.
Methods Thymic output was studied by measuring levels of T-cell receptor rearrangement excision circles (TREC) in peripheral blood lymphocytes, using a real-time quantitative PCR assay. Recombinant viruses containing pre-therapy or post-therapy HIV-1 protease domains were evaluated for viral infectivity in a quantitative single-cycle assay.
Results Eighteen HIV-1-infected children who showed a significant increase in CD4 T-cell count after therapy were studied; HIV-1 plasma viraemia was substantially suppressed in 12 children (virological responders), but not in the other six (virological non-responders). TREC were quantified at baseline, and sequentially during the first 12 months of therapy. Both virological responders and non-responders showed an increase in TREC levels that was inversely correlated with baseline TREC and CD4 T cell counts. Changes in TREC positively correlated with CD4 T-cell count increases in virological responders, but not in non-responders; moreover, the ratios between TREC and CD4 T-cell count increases were higher in non-responders than in responders, suggesting a persistence of peripheral CD4 T-cell loss in the former. Drug-resistant viruses with reduced replicative capacity were documented in three out of six non-responders.
Conclusions These findings indicate that recovery of thymic function is a pivotal event in immune reconstitution, and suggest that CD4 T-cell increase despite persistent viraemia is sustained by a continuous thymic output that compensates peripheral CD4 T-cell depletion which might be slowed down by emerging viruses with reduced fitness.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
HIV-1; children; antiretroviral therapy; thymus; viral replication
Elenco autori:
L. Ometto, D. De Forni, F. Patiri, V. Trouplin, F. Mammano, V. Giacomet, C. Giaquinto, D. Douek, R. Koup, A. De Rossi
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