Experimental human pneumococcal carriage in adults with HIV in Malawi

Background: People living with HIV (PLHIV) in sub-Saharan Africa exhibit high rates of pneumococcal carriage compared to HIV-uninfected adults, despite antiretroviral therapy. We established a novel controlled human infection model of experimental pneumococcal carriage in people living with HIV to understand carriage dynamics in this at-risk population. Methods: Seventy-five virally suppressed and clinically stable PLHIV and 75 HIV-uninfected controls were inoculated with escalating doses of pneumococcus serotype 6B. Carriage acquisition and density were determined by microbiological culture of nasal wash samples collected before and up to 14 days after inoculation. Adverse events were identified by active and passive surveillance. Participant-reported acceptability was established using a Likert scale. Findings: No serious adverse events occurred. Mild adverse events were similar between groups (19% [14/75] in PLHIV, 13% [10/75] in HIV-uninfected; p=0.505). More than 90% of participants reported acceptability with all study procedures. Experimental carriage occurred in 21% (16/75) of PLHIV compared with 36% (27/75) of HIV-uninfected participants (adjusted odds ratio 0.39 [95% CI 0.16-0.91]). Among PLHIV without detectable cotrimoxazole, 28% (8/29) acquired experimental carriage. Carriage clearance rates were lower in PLHIV (hazard ratio 0.44 [95% CI 0.14-1.42]). Interpretation: In carefully selected PLHIV with effective viral suppression and clinical stability experimental pneumococcal carriage acquisition did not exceed that in HIV-uninfected adults, even after accounting for antibiotic use, natural pneumococcal co-colonisation, and sociodemographic differences. These findings suggest that high carriage prevalence in PLHIV in sub-Saharan Africa may be driven more by prolonged carriage duration than increased susceptibility to acquisition. This model provides a platform to investigate mechanisms underlying carriage susceptibility and impaired clearance in PLHIV and to evaluate interventions aimed at reducing the carriage burden in sub-Saharan Africa. Funding: Wellcome Trust