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


CONCLUSIONS
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.
Vigano
A
A
Pediatric Department IV, University of Milan, Ospedale Luigi Sacco, Italy. alevig@mailserver.unimi.it
Vella
S
S
Saresella
M
M
Vanzulli
A
A
Bricalli
D
D
Di Fabio
S
S
Ferrante
P
P
Andreotti
M
M
Pirillo
M
M
Dally
L G
LG
Clerici
M
M
Principi
N
N
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D015331:Cohort Studies; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000627:therapeutic use; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D009929:Organ Size; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D013950:Thymus Gland / Q000473:pathology*; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D018119:Stavudine; D016049:Didanosine