A 7-valent CRM197 conjugate pneumococcal vaccine (PCV)-induced immune response were evaluated in all Greek symptomatic HIV-1 infected children and 21 age-matched controls. PCV immunogenicity was inferior in HIV patients compared with the controls although differences in geometric mean concentrations (GMC) were not significant (P>.05). Immune responses were strikingly different after anamnestic immunization, given in all study subjects, 12 months later. HIV-positive children achieved lower GMC for all serotypes compared with the controls (P=.002) and avidity for all except serotype 6B was inferior compared to baseline. Long-term PCV effectiveness is expected to be reduced among symptomatic HIV-1 infected children.