Background Adults living with human immunodeficiency virus (ALWHIV) taking antiretrovirals (ART) have higher pneumococcal nasopharyngeal carriage and disease than adults without HIV (HIV–). To assess factors influencing high pneumococcal carriage prevalence and generate evidence base for evaluating future pneumococcal conjugate vaccine (PCV) strategies in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting, at least 10 years after introducing infant PCV13 in routine immunisation. Methods We collected longitudinal nasopharyngeal swabs from age-and sex-matched 18–45–year–old HIV– adults, ALWHIV with ART experience of more than 1 year (ART>1y) or less than 3 months (ART<3m) from communities around Blantyre, Malawi. Samples were taken at baseline, and then weekly during the 16 visits over the study period. We employed classical culture microbiology to detect pneumococcal carriage and determined pneumococcal serotypes using latex agglutination. We fitted trajectories of serotype colonisation to multi–state Markov models to capture the dynamics of pneumococcal carriage adjusting for age, sex, number of household children under 5 years–old (<5y), social economic status (SES) and seasonality. Results At baseline, 65 adults were enrolled in each of the three HIV groups irrespective of pneumococcal carriage status, totalling 195 adults of whom 51.8% were females, 25.6% cohabited with >1 child <5y, and 41.6% lived in low SES. Median age was 33y (interquartile range [IQR]: 25-37y). Baseline pneumococcal carriage prevalence of all serotypes as 31.3% of which non-PCV13 serotypes (NVT) (26.2%) was higher than PCV13 serotypes (VT) (5.1%). In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (NVT [Hazard Ratio [HR]: 1.53, 95%CI:1.17-2.01]; VT [1.96, 1.11-3.49]). It was also higher in low than high SES (NVT [1.38, 1.03-1.83]; VT [2.06, 1.13-3.77]), in adults living with 2+ than 1 child <5y (VT [1.78, 1.05-3.01]), and in ALWHIV on ART>1y than HIV- adults (NVT [1.43, 1.01-2.02]). Moreover, ALWHIV on ART>1y cleared pneumococci slower than HIV- adults ([0.65, 0.47-0.90]). Residual VT 19F and 3 were highly acquired although NVT remained dominant. Conclusions The disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART>1y is likely due to impaired nasopharyngeal clearance resulting in prolonged carriage. Our findings provide baseline estimates for comparison of pneumococcal carriage dynamics after new PCV strategies in ALWHIV are implemented. Key words: Pneumococcal acquisition, Pneumococcal duration, Serotype, Human immunodeficiency virus, Modelling, Malawi

The authors have declared no competing interest.

The authors thank all community study participants, and the study staff for their support and co-operation during the study. This work was supported by an African Research Leader (ARL) award [MR/T008822/1 to KCJ. This ARL award is jointly funded by the UK Medical Research Council (MRC) and the UK Foreign Commonwealth and Development Office (FCDO) under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. A Wellcome Strategic award number 206545/Z/17/Z supports MLW. The funders were not involved in the design of the study; in the collection, analysis, and interpretation of the data; and in writing the manuscript. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funders.

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Study ethics approval was granted by the Malawi National Health Sciences Research Ethics Committee (NHSRC) (21/24/2680) and the Liverpool School of Tropical Medicine Research Ethics (21-035).

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