Association Of Cd4(+) T-Lymphocyte Counts And New Thymic Emigrants In Hiv-Infected Children During Successful Highly Active Antiretroviral Therapy

Background: In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/ml,, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIA-1 DNA) and equal or greater CD4(+) T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART.Objective: To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4(+) T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression.Methods: T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART.Results: There was,I positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4(+) T-lymphocyte percentages (P < .02) and naive CD4(+) T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA.Conclusion: To maintain adequate levels of CD4(+) T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4(+) T lymphocytes in the presence of persistent virus. Clinical implications: The TREC level is a useful marker of thymic function in HIV-infected children.