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

BACKGROUND: 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 endpoint 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; 95% CI 0.7‐3.3). 22 isolates (88%) were of vaccine‐specific serogroups with 15 events in the vaccine arm compared with seven in the placebo arm (HR 2.10; 0.9‐5.2). All pneumococcal 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 pneumococcal 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 pneumococcal disease in vaccine recipients may necessitate a reappraisal of this intervention in other settings.