Estimating pneumococcal carriage dynamics in adults living with HIV in a mature infant pneumococcal conjugate vaccine program in Malawi, a modelling study

BackgroundAdults 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. MethodsWe 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. ResultsAt 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. ConclusionsThe 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. Author summaryWe assessed rates of pneumococcal serotype carriage acquisition and clearance by fitting multi-state Markov models to pneumococcal colonisation trajectories comprising 3,152 nasopharyngeal samples from 195 adults aged 18-45 years in Blantyre, Malawi. Substantial acquisitions of VT and NVT in females and those living under low socioeconomic status were estimated, in addition to VT acquisition among adults living with at least two children in the house and NVT acquisition among ALWHIV on ART>1y. ALWHIV on ART>1y cleared overall carriage, and NVT in particular, slower than their HIV-counterparts. Residual VT serotypes 19F and 3 were highly acquired whereas 19A, 3, and 6A were carried for longer durations, still, NVT serotypes remained dominant, suggesting that PCV strategy in ALWHIV should consider expanded serotype coverage to tackle the remaining preventable burden of pneumococcal carriage and subsequent disease. The contribution of NVT carriage to the disproportionately high carriage prevalence in ALWHIV is substantial, though the underlying causal drivers for prolonged duration of carriage in ALWHIV on ART>1y warrant further investigation. We generate the evidence base for evaluating future pneumococcal vaccine strategies in ALWHIV.