High propensity for multidrug-resistant pneumococcal shedding among adults living with HIV on stable antiretroviral therapy in Malawi

Abstract Background People living with HIV (PLHIV) on antiretroviral therapy (ART) are still at risk of pneumococcal disease and have over two-fold higher pneumococcal carriage prevalence than HIV-uninfected adults (HIV- adults). Carriage is a risk factor for pneumococcal disease, antimicrobial resistance (AMR) emergence, and transmission. Therefore, we tested whether the high prevalence of pneumococcal carriage in PLHIV on ART is associated with increased bacterial density, shedding and AMR. Methods We recruited asymptomatic PLHIV on ART for more than one year (PLHIV-ART>1yr) and HIV- adults. Nasopharyngeal swabs were collected on days 3, 7, 14, 21, and 28, followed by monthly collections for 12 months, while shedding samples were collected on days 3, 21, and 28. Peripheral blood was collected on day 3 to measure CD4 count and HIV viral load. Pneumococcal carriage density and shedding were assessed using standard bacterial culture, and multiple carriage was detected through whole plate sweep sequencing. AMR profiling was conducted using disk diffusion and E-test. Findings PLHIV-ART>1yr had a higher propensity for high-density carriage (adjusted Odds Ratio 1.67, 95% CI 1.07-2.60, p=0.023). Moreover, PLHIV-ART>1yr are more likely to shed pneumococci than HIV- adults (aOR 2.52, 95% CI 1.06-6.00, p=0.037), with carriage density identified as an important risk factor for shedding (aOR 3.35, 95% CI 1.55-7.24, p=0.002). Aerosol shed isolates from PLHIV-ART>1yr were mostly multidrug-resistant (62% 18/29, 95% CI 48%-77%). Interpretation These findings indicate that PLHIV-ART>1yr remain at high risk of pneumococcal disease and could also be an important reservoir for shedding multidrug-resistant pneumococci.