Background: HAART has been shown to increase T-cells and T-cell rearrangement excision circle (TREC) levels in HIV-infected adults and children with viral suppression. However, there is limited data on the effect of HAART on thymic output as indicated by TREC levels during pregnancy. PACTG 353 was a phase I prospective study of PK, safety and antiviral activity of NFV/3TC/ZDV in 31 HIV-infected pregnant women and their infants; a significant increase in CD4 T-cells was observed in women between baseline and delivery.

Methods: We quantitated TREC levels in PBMC from 19/28 women completing PACTG 353 with available PBMCs at baseline, delivery and 6–12 weeks post-partum. Thirteen (13) of 19 of the women were naïve to antiretroviral therapy at study entry. DNA was prepared from cryo-preserved PBMC by guanidinium lysis/column purification. TRECs were quantitated in one microgram patient PBMC DNA using the Taqman real-time PCR system. All reactions were run in triplicate and TREC copy numbers were determined by comparison with a standard curve.

Results: At baseline, the median (25^th and 75^th percentile) maternal CD4 T-cell count was 403 (266 and 543) and the median peripheral blood TREC level was 1,634 (660 and 5,367) copies/mg PBMC DNA. At the time of delivery, the median CD4 T-cell count among the 19 women studied increased to 486 (344 and 689) (p < 0.01) and median TREC levels increased to 4,998 (1,347 and 16,289) /mg (p < 0.01). Following delivery, maternal CD4 and TREC levels showed slight but not significant decreases in median to 476 (349 and 781) and 3,785 (1642 and 8550) /mg respectively. However, TREC levels at 6–12 weeks post-partum still remained significantly higher than baseline levels (p < 0.01). Antiretroviral naïve mothers showed a larger-fold increase in TRECs over gestation than non-naive mothers (6.8-fold vs 1.5-fold); however, due to small population size, this difference was not statistically significant. The largest increases in PBMC TREC levels were found among women who were naïve to antiretroviral therapy at entry and had low initial TREC copy numbers.

Conclusions: These data indicate that HAART therapy can promote increased thymic output and/or prolong the life of naïve T-cells in HIV-infected pregnant women treated during gestation/post-partum.