Live-attenuated influenza vaccine (LAIV) prevents significantly more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the T cell responses to LAIV or TIV in HIV-infected children. IFN-gamma-ELISPOT for the three vaccine-contained influenza strains, two mismatched strains, and phytohemagglutinin (PHA), was performed at 0, 4, and 24 weeks postimmunization in 175 HIV-infected children randomly assigned to LAIV or TIV. The contribution of CD8 T cells to the influenza-specific response (CD8-ELISPOT) was evaluated by CD8-cell depletion. CD8 T cells accounted for > or =87% of the total influenza-ELISPOT. At baseline, total influenza-ELISPOT and CD8-ELISPOT values were similar or higher in TIV compared with LAIV recipients. Four and 24 weeks after TIV, total influenza-ELISPOT and CD8-ELISPOT results were significantly lower than baseline results (p < or = 0.001). Responses to PHA also tended to decrease at 4 weeks after TIV (p = 0.06), but rebounded to baseline levels at 24 weeks. Four weeks after LAIV, total influenza-ELISPOT responses to vaccine-contained strains A H3N2 and B significantly decreased. Other ELISPOT values at 4 weeks and all values at 24 weeks were similar to the baseline values. At 4 and 24 weeks, TIV compared to LAIV administration resulted in a significantly greater decrease in influenza-specific ELISPOT values for vaccine-contained influenza A strains (p < or = 0.02). Responses to PHA also tended to decrease more in TIV recipients (p = 0.07). HIV-infected children immunized with TIV had significant and persistent decreases in ELISPOT responses to influenza. LAIV administration suppressed ELISPOT responses less. The clinical significance of these findings deserves further study.