TY - JOUR
T1 - Association of CD4 + T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy
AU - Saitoh, Akihiko
AU - Singh, Kumud K.
AU - Sandall, Sharsti
AU - Powell, Christine A.
AU - Fenton, Terrence
AU - Fletcher, Courtney V.
AU - Hsia, Karen
AU - Spector, Stephen A.
N1 - Funding Information:
Supported by the Pediatric AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (AI-39004, AI-27563, AI-33835, AI-41110, AI-36214 [Virology Core UCSD Center for AIDS Research], AI-32921) and Bristol-Myers Squibb.
PY - 2006/4
Y1 - 2006/4
N2 - 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. 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.
AB - 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. 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.
KW - CD4 T lymphocytes
KW - HAART
KW - HIV-1 intracellular DNA
KW - T-cell receptor excision circles
KW - children
KW - immune reconstitution
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U2 - 10.1016/j.jaci.2006.01.013
DO - 10.1016/j.jaci.2006.01.013
M3 - Article
C2 - 16630951
AN - SCOPUS:33646045847
SN - 0091-6749
VL - 117
SP - 909
EP - 915
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -