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 (HIV-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 a 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.


CONCLUSIONS
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.


CONCLUSIONS
The TREC level is a useful marker of thymic function in HIV-infected children.
Saitoh
Akihiko
A
Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, La Jolla 92093-0672, USA.
Singh
Kumud K
KK
Sandall
Sharsti
S
Powell
Christine A
CA
Fenton
Terrence
T
Fletcher
Courtney V
CV
Hsia
Karen
K
Spector
Stephen A
SA
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D012367:RNA, Viral / Q000097:blood; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology*
D004279:DNA, Viral; D012367:RNA, Viral; D004247:DNA