BACKGROUND: Invasive pneumococcal disease (IPD) is an important cause of morbidity among individuals infected with human immunodeficiency virus (HIV). We described incidence and risk factors for IPD in HIV-infected and uninfected individuals.

METHODS: Nationwide population-based cohort study of HIV-infected adults treated at all Danish HIV treatment centers during 1995-2012. Nineteen population-matched controls per HIV-infected individual were retrieved. The risk of IPD was assessed using Poisson regression.

RESULTS: The incidence of IPD was 304.7 cases per 100 000 person-years of follow-up (PYFU) in HIV-infected and 12.8 per 100 000 PYFU in HIV-uninfected individuals. After adjusting for confounders, HIV infection (relative risk [RR], 24.4 [95% confidence interval [CI], 23.7-25.1]), male sex (RR, 1.20 [95% CI, 1.16-1.24]), increasing age (per year) (RR, 1.03 [95% CI, 1.03-1.04]), and calendar period (pre-cART RR, 2.80 [95% CI, 2.70-2.91] compared with late cART) were significantly associated with an increased risk of IPD. Among HIV-infected individuals, male sex (RR, 1.57 [95% CI, 1.49-1.66]), smoking (RR, 1.34 [95% CI, 1.26-1.42]), and injecting drug use (RR, 2.51 [95% CI, 2.26-2.67]) were associated with an increased risk of IPD. Detectable viral loads (RR, 1.88 [95% CI, 1.79-1.98]) and a relative fall in CD4 T-cell counts were also associated with an increased risk (≥500 to 350-500 CD4 T cells/µL: RR, 1.29 [95% CI, 1.21-1.37] and <100 cells/µL: RR, 7.4 [95% CI, 6.87-8.02]). The risk of IPD declined over time, although this was not the case for IDUs where the risk remained unchanged.

CONCLUSIONS: The incidence of IPD in HIV-infected individuals remained significantly higher than the incidence observed in non-HIV-infected subjects, despite the widespread use of cART. IDUs have a persistently high risk of IPD. Injecting drug use, smoking, and the receipt of cART are suitable targets for preventive measures in the future.