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The immunogenicity and safety of 2 doses of pneumococcal conjugate vaccine (PCV) and 1 dose of pneumococcal polysaccharide vaccine (PPV) were evaluated in human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART).Children 2 to <19 years, receiving stable HAART for ≥3–6 months, with HIV RNA PCR <30,000–60,000 copies/mL, received 2 doses of PCV and 1 dose of PPV at sequential 8-week intervals. Antibodies to pneumococcal serotypes (STs) 1 (PPV only) and 6B, 14, 19F, and 23F (PCV and PPV) were measured by ELISA.Two hundred sixty-three subjects were enrolled, of whom 225 met criteria for inclusion in the primary dataset. Antibody concentrations were low at entry, despite previous PPV in 75%. After vaccination, 76%–96% had concentrations ≥0.5 μg/mL and 62–88% ≥1.0 μg/mL to the 5 STs (geometric mean concentrations [GMCs] = 1.44–4.25 μg/mL). Incremental gains in antibody concentration occurred with each vaccine dose. Predictors of response included higher antibody concentration at entry, higher immune stratum (based on nadir CD4% before HAART and CD4% at screening), lower entry viral RNA, longer duration of the entry HAART regimen, and age <7 years. Response was more consistently related to screening CD4% than nadir CD4%. Seven percent had vaccine-related grade 3 events, most of which were local reactions.Two PCVs and 1 PPV were immunogenic and safe in HIV-infected children 2 to <19 years who were receiving HAART. Responses were suggestive of functional immune reconstitution. Immunologic status based on nadir and, especially, current CD4% and control of HIV viremia were independent determinants of response.