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

Design: Despite significant rises in total CD4 T cells, the process of immu ne reconstitution in adults with HIV infection treated with potent antiretr oviral treatment results in a rather slow increase in phenotypically naive lymphocytes. In children more than in adults, thymic function may be at lea st partly restored when disease-induced immunosuppression is attenuated by pharmacological means. Methods: Twenty-five vertically infected and antiretroviral-experienced [zi dovudine (ZDV)/ZDV plus didanosine (ddl)] children were prospectively follo wed during 12 months of treatment with lamivudine (3TC), stavudine (d4T) an d indinavir (IDV). The plasma HIV Viral load and phenotypic and functional cellular immunity-defining parameters were examined. The relationship betwe en the degree of immune reconstitution and thymus volume assessed by nuclea r 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 signific ant 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 reconstit ute families almost completely absent at baseline, and a substantial improv ement of antigen-specific responses by peripheral blood lymphocytes. The ri se 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 rec onstitution of the peripheral pool of T cells in vertically HIV-infected ch ildren treated with potent antiretroviral regimens. (C) 2000 Lippincott Wil liams & Wilkins.