350 HIV-specific Cytotoxic T-lymphocyte Epitope Responses in HIV-infected Children on HAART N. Ching*, B. Ank, O. Yang, K. Nielsen, J. Deville, Y.J. Bryson Univ of California at Los Angeles
Background: HIV-specific Cytotoxic T-lymphocyte (CTL) epitope responses have been reported in adults treated early in HIV infection associated with containment of acute viremia and in those with chronic infection. However, data on HIV CTL responses in infants and children have been limited with detection rare in young infants. The effect of HAART on these responses may also vary with the time of initiation of therapy and the durability and level of virus suppression.
Methods: We initiated a cross-sectional study of HIV specific CTL responses to peptide pools in 9 HIV infected children on HAART, ages 3-14.5 yrs. We included 5 children with prolonged suppression of plasma HIV RNA (< 50 copies/ml) for 3 to 6 yrs as compared to 4 children with persistent viremia (mean HIV RNA 279,795 copies/ml) despite HAART. Nonspecifically expanded CD8+ PBMC from HIV-infected children were tested in ELISpot assays using overlapping peptides in screening HIV peptide pools of 16 peptides or less. Standard ELISpot assays measuring IFN-gamma production were performed and then analyzed with computer image analysis by an ELISpot reader (CTL Technologies). Cells without peptide and phytohemagglutinin stimulated cells served as negative and positive controls.
Results: Overall, we detected HIV specific CTL responses to HIV epitopes in 7/9 patients; 4/4 children with persistent viremia had HIV specific CTL response to 2-4 peptide pools, including nef, pol, env, gag, nef, rev and vpr. In contrast, 5/5 children with prolonged viral suppression of plasma had a decreased response to HIV CTL peptide pools. Two (2) children had no detectable response, and 3 had a response to only 1 or 2 peptide pools (pol, env, and nef).
Conclusions: We were able to detect HIV-specific CTL epitope responses in the majority of children on HAART 7/9 (77%). These responses differed by degree of viral suppression. Active viral replication may be necessary to maintain a detectable CTL response. Further prospective studies will be necessary to evaluate CTL responses overtime in children on HAART.
