Relationship between changes in thymic emigrants and cell-associated HIV-1 DNA in HIV-1-infected children initiating antiretroviral therapy.
OBJECTIVE
To investigate the relationship between cell-associated HIV-1 dynamics and recent thymic T-cell emigrants, HIV-1 DNA and T-cell receptor rearrangement excision circles (TREC, a marker of recent thymic emigrants) were measured in peripheral blood mononuclear cells in 181 samples from 33 HIV-1-infected children followed for 96 weeks after antiretroviral therapy (ART) initiation.


RESULTS
At baseline, HIV-1 DNA was higher in children with higher TREC (P=0.02) and was not related to age, CD4 or HIV-1 RNA in multivariate analyses (P>0.3). Overall, TREC increased and HIV-1 DNA decreased significantly after ART initiation, with faster HIV-1 DNA declines in children with higher baseline TREC (P=0.009). The greatest decreases in HIV-1 DNA occurred in children with the smallest increases in TREC levels during ART (P=0.002). However, this inverse relationship between changes in HIV-1 DNA and TREC tended to vary according to the phase of HIV-1 RNA decline (P=0.13); for the same increase in TREC, HIV-1 DNA decline was much smaller during persistent or transient viraemia compared with stable HIV-1 RNA suppression.


CONCLUSIONS
Overall, these findings indicate that TREC levels predict HIV-1 DNA response to ART and suggest that immune repopulation by thymic emigrants adversely affects HIV-1 DNA decline in the absence of persistent viral suppression, possibly by providing a cellular source for viral infection and replication.
De Rossi
Anita
A
Department of Oncology and Surgical Sciences, AIDS Reference Centre, Padova, Italy.
Walker
A Sarah
AS
De Forni
Davide
D
Klein
Nigel
N
Gibb
Diana M
DM
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral