Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume.

Publication Type
Journal Article
Year of Publication
Vigano, A; Vella, S; Saresella, M; Vanzulli, A; Bricalli, D; Di Fabio, S; Ferrante, P; Andreotti, M; Pirillo, M; Dally, L G; Clerici, M; Principi, N
Date Published
2000 Feb 18
Anti-HIV Agents; CD4 Lymphocyte Count; Child; Cohort Studies; Didanosine; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Organ Size; Reverse Transcriptase Inhibitors; Stavudine; Thymus Gland; Viral Load; Zidovudine

DESIGN: Despite significant rises in total CD4 T cells, the process of immune reconstitution in adults with HIV infection treated with potent antiretroviral treatment results in a rather slow increase in phenotypically naive lymphocytes. In children more than in adults, thymic function may be at least partly restored when disease-induced immunosuppression is attenuated by pharmacological means.

METHODS: Twenty-five vertically infected and antiretroviral-experienced [zidovudine (ZDV)/ZDV plus didanosine (ddl)] children were prospectively followed during 12 months of treatment with lamivudine (3TC), stavudine (d4T) and indinavir (IDV). The plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined. The relationship between the degree of immune reconstitution and thymus volume assessed by nuclear magnetic resonance was also examined.

RESULTS: An early and steep increase in CD45RA+62L+ T cells was observed in parallel with a sustained decrease in plasma HIV RNA levels and a significant rise in total CD4 T cells. This increase was significantly greater than that observed in CD4+CD45RO+ T cells. Analysis of the CD4 T cell receptor (TCR) beta repertoire and T helper function showed the ability to reconstitute families almost completely absent at baseline, and a substantial improvement of antigen-specific responses by peripheral blood lymphocytes. The rise in CD4 cells and in CD4+CD45RA+62L+ T cells was statistically associated with changes in thymus size observed over time.

CONCLUSION: These data suggest a relevant contribution of the thymus to reconstitution of the peripheral pool of T cells in vertically HIV-infected children treated with potent antiretroviral regimens.