Background:  Possible origins of increased T cells in HIV⁺ patients on HAART include the thymus or redistribution of cells from other tissues. We analyzed TREC in previously naïve children treated with HAART in order to determine if increases in circulating T cells are associated with numbers of recent thymic emigrants.

Methods:  PACTG P1021 participants received a once daily regimen of emtricitabine (FTC), efavirenz (EFV), and didanosine (ddI) for 1 to 3 years. HIV-infected children were stratified into 2 age groups with group 2 participants ranging from 3 to 12 years of age and group 3 participants ranging from 13 to 21 years of age. Peripheral blood mononuclear cells (PBMC) from study children were collected and separated into CD4⁺ and CD8⁺ T cell subsets by using the Rosette-Sep method at baseline and weeks 16, 24, and 48. DNA was extracted from CD4⁺ and CD8⁺ cell populations using Qiagen Blood columns. TREC were amplified by real-time polymerase chain reaction (PCR) in an ABI PRISM 7700 using Taqman reagents. All samples were amplified in triplicate and TREC were quantified by comparison with an external standard curve.

Results:  Samples were available for TREC quantitation from 21 children in group 2 and 16 children in group 3 across the study period and from a total of 25 children at baseline through week 48. Across the study period, CD4⁺ TREC were found to correlate positively with CD4⁺ count, CD4⁺ percentage, naïve CD4⁺ cells and showed a negative correlation with activated CD4⁺ cells (all p <0.0001). CD8⁺ TREC did not show a significant correlation with CD8⁺ count but did show positive correlations with CD8⁺ percentage, naïve CD8⁺ cells and a negative correlation with activated CD8⁺ cells (all significant p <0.0001). At baseline, CD4⁺ TREC were higher than CD8⁺ TREC across both age groups (median [25^th to 75^th percentile] 6540 [1780 to 29,007] CD4 vs 2507 [603 to 11,280] CD8 TREC/million cells, p = NS). At week 48 levels of both CD4⁺ and CD8⁺ TREC had risen significantly across both age groups (51,236 [27,667 to 83,814] CD4 TREC and 32,135 [15,386 to 49,354] CD8 TREC/million cells, both p <0.0001).

Conclusions:  The correlations between CD4⁺/CD8⁺ cell count and/or naïve CD4⁺/CD8⁺ and CD4⁺/CD8⁺ TREC over the course of the study indicates that thymic activity is at least partially responsible for the reconstitution of T cells observed in study participants. The increases in CD4⁺/CD8⁺ TREC observed among children in both age groups also indicate that even older HIV-infected children retain thymic function and can experience T cell reconstitution following treatment with HAART.