Session 41Poster Presentations CD4 T-Cell Responses to HIV Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall D
299 Robust Gag-specific T-helper Response Associated with Viral Control in Pediatric HIV Infection M. E. Feeney*1,2, C. L. Day1, K. A. Roosevelt1, K. McIntosh2, S. Burchett2, C. Mao2, P. J. R. Goulder1,3, B. D. Walker1 1Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA; 2Children's Hosp, Boston, MA; and 3Peter Medawar Bldg for Pathogen Res, Oxford, UK
Background: Adults with long-term nonprogressive HIV infection frequently possess strong HIV-specific T-helper responses. A robust proliferative response to p24 antigen has been shown to correlate with low viral load in HIV-infected adults, but strong responses are seldom detected in those with progressive infection and they are not generally reconstituted on HAART. To date, the role of HIV-specific T-helper responses has not been well studied in children.
Methods: We characterized gag-specific CD4 responses among 24 perinatally HIV-infected subjects, including 2 children who spontaneously control viremia after stopping antiretroviral therapy, 14 children with a nondetectable viral load on HAART, and 8 viremic children. Gag-specific T-helper activity was assessed by lymphoproliferative assay and responses were mapped by IFNg ELISpot. Secretion of IFNg, IL-2, and TNFa by gag-specific CD4 cells was assessed by intracellular staining. The T-helper responses of children on HAART were compared to those of viremic children and to HAART-treated adults.
Results: Robust proliferative responses were detected in the two children who spontaneously control viremia, suggesting an important functional role for this response. Among children with nondetectable viremia on HAART, 12 of 14 subjects demonstrated a significant p24 proliferative response (median p24 SI = 19.6). In contrast, only 1 of 8 viremic children possessed a significant response (median p24 SI = 3.1; p = 0.004) T-helper responses among children on HAART were both more frequent (p=0.039) and of greater magnitude (p = 0.016) than among HAART-treated adults. The breadth of the gag-specific CD4 responses among the pediatric subjects was highly variable, but one subject exhibiting spontaneous viral control possessed a strikingly broad response.
Conclusions: Strong HIV-specific T-helper responses were detected in perinatally HIV-infected children who spontaneously control HIV viremia, and also in a large majority of children with suppressed viremia on HAART. Although longitudinal studies are needed, these data suggest that children may have a greater intrinsic capacity to reconstitute HIV-specific immunity than adults, and may be excellent candidates for immune-based therapies. Further studies are also needed to determine the functional role of these CD4 cells and the clinical significance of this preserved functional capacity.
