23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind; randomised and placebo controlled trial

ABSTRACT

Infection with streptococcus pneumoniae is a frequent and serious problem for HIV-immunosuppressed adults. Vaccination is recommended in the USA and europe; but there are no prospective data that show vaccine efficacy. Methods: 1392 (937 female) HIV-1-infected adults in Entebbe; Uganda; were enrolled. 697 received 23-valent pneumococcal polysaccharide vaccine and 695 received placebo. The primary end point was first event invasive pneumococcal disease. Secondary endpoints included vaccine serogroup-specific invasive disease; all (probable and definite) pneumococcal events; all-cause pneumonia; and death. Findings: First invasive events occurred in 25 individuals (24 bacteraemias; one pyomyositis); 15 in the vaccine arm and ten in the placebo arm (hazard ratio [HR] 1.47; 95CI 0.7-3.3). 22 isolates (88) were of vaccine-specific serogroups with 15 events in the vaccine in the vaccine arm compared with seven in the placebo arm (HR 2.10; 0.9-5.2). All pnwumococcal events had a similar distribution (20 vs 14; HR 1.41; 0.7-2.8) though all-cause pneumonia was significantly more frequent in the vaccine arm (40 vs 21; HR 1.89; 1.1-3.2). Mortality was unaffected by vaccination. Interpretation: 23-valent pnwumococcal polysaccharide vaccination is ineffective in HIV-1 infected Ugandan adults and probably has little; or no; public health value elsewhere in sub-Saharan Africa. Increased rates of pnwumococcal disease in vaccine recipeients may necessitate a reappraisal of this intervention in other settings