High Propensity for Multidrug-Resistant Pneumococcal Shedding Among Adults Living With HIV on Stable Antiretroviral Therapy in Malawi

Background. People living with human immunodeficiency virus (HIV; PLHIV) on antiretroviral therapy (ART) are still at risk of pneumococcal disease and have over 2-fold higher pneumococcal carriage prevalence than HIV-uninfected (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 >1 year (PLHIV-ART>1y) and HIV− adults. Nasopharyngeal swab samples 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 samples were collected on day 3 to measure CD4 cell count and HIV viral load. Pneumococcal carriage density and shedding were assessed using standard bacterial culture, multiple carriage was detected using whole-plate sweep sequencing, and AMR profiling was conducted using disk diffusion and Etest. Results. PLHIV-ART>1y had a higher propensity for high-density carriage (adjusted odds ratio, 1.67 [95% confidence interval (CI), 1.07–2.60]; P = .02). Moreover, PLHIV-ART>1y are more likely to shed pneumococci than HIV− adults (adjusted odds ratio, 2.52 [95% CI, 1.06–6.00]; P = .04), with carriage density identified as an important risk factor for shedding (3.35 [1.55–7.24]; P = .002). Aerosol shed isolates from PLHIV-ART>1y were mostly multidrug resistant (18 of 29 [ 62%; 95% CI, 48%–77%]). Conclusions. These findings indicate that PLHIV-ART>1y remain at high risk of pneumococcal disease and could also be an important reservoir for shedding multidrug-resistant pneumococci.