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Full T-cell reconstitution after long-term HAART without signs of accelerated aging of the T-cell pool in adults and children

Abstract:

We studied whether full T-cell reconstitution can in principle be achieved in HIV-infected adults and children with complete long-term virological control by HAART. To study quantitative and qualitative T-cell recovery a comprehensive analysis was performed, including analyses of naive, memory and effector CD4+ and CD8+ T-cell recovery, activation and proliferation markers, CD31 expression, TREC numbers and telomere lengths. CD4+ T-cell counts in children recovered to age-matched control values within 1 year, even when HAART was initiated at an extremely lymphopenic stage. In adults with CD4+ T-cell counts> 200 cells/µl at HAART initiation CD4+ T-cell counts recovered within 1 year of therapy. Adults with lower CD4+ T-cell numbers at HAART initiation persistently sustained lower counts than adults with high pre-therapy CD4+ T-cell counts throughout follow-up, but nevertheless normalized CD4+ T-cell counts after 7 years of HAART. Absolute numbers of naive CD4+ T cells normalized in all children and in adults with high baseline CD4+ T-cell counts, whereas naive CD4+ T-cell counts in adults with low baseline CD4+ T-cell numbers lagged behind. After long-term HAART the TREC content and TREC numbers in adults and children had returned to the levels of age-matched controls. Restoration of the nearly empty T-cell pool apparently did not interfere with T-cell aging, because evidence neither for accelerated aging nor for rejuvenation of the T-cell pool was obtained. Strikingly, the proliferation marker Ki67 had normalized after long-term HAART in children, but remained elevated in HIV-infected adults after long-term treatment …