Background: Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIVunexposed- uninfected (HUU) children. Methods:Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9-10 months). Immune responses, assessed using enzyme-linked immunosorbent and functional assays, and safety were evaluated up to 14 months post-booster. Results: Of 83, 101, and 100 children enrolled in HIV+, HEU, and HUU groups, 70, 91, and 93 were included in according-toprotocol immunogenicity cohort. For each vaccine-serotype, percentages of children with antibody concentrations ≥0.2μg/mL were ≥97% 1 month post-primary vaccination and ≥98.5% 1 month post-booster (except for 6B and 23F at both timepoints). Postprimary vaccination, functional antibody responses were lower in HIV+ children: for each vaccine-serotype, percentages of children with opsonophagocytic activity (OPA) titres ≥8 were ≥72%, ≥81%, and ≥79% for HIV+, HEU, and HUU children. Post-booster, ≥87% of children in each group had OPA titres ≥8. Reactogenicity was similar across groups. Thirty one (37%) HIV+, 25 (25%) HEU, and 20 (20%) HUU children reported ≥1 serious adverse event. Five HIV+ and 4 HEU children died. One death (sudden infant death syndrome; HEU group; 3 days post-dose 1) was considered potentially vaccine-related. Conclusion: PHiD-CV was immunogenic and well-tolerated in HIV+, HEU, and HUU children, and has the potential to provide substantial benefit irrespective of HIV infection status.
