Characterization of bacterial and viral pathogens in the respiratory tract of children with HIV-associated chronic lung disease: a case‒control study

ABSTRACT Introduction Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naïve children with (HCLD+) and without HCLD (HCLD-) established on antiretroviral treatment (ART). Methods Nasopharyngeal swabs collected from HCLD+ (defined as forced-expiratory-volume/second<-1.0 without reversibility postbronchodilation) and age-, site-, sex- and duration-of-ART-matched HCLD-enrolled in Zimbabwe and Malawi (BREATHE trial- NCT02426112 ) were tested for seven bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and five viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using qPCR (Fluidigm). Fisher’s exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively. Results A total of 345 participants (287 HCLD+, 58 HCLD-; median age, 15.5 years [IQR=12.8–18], females, 52%) were included in the final analysis. SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were more prevalent in HCLD+ patients than in HCLD-patients. Viruses (predominantly HRV) were detected only in HCLD+ participants. HI (1.55×10 4 CFU/ml vs. 2.55×10 2 CFU/ml, p = 0.006) and MC (1.14×10 4 CFU/ml vs. 1.45×10 3 CFU/ ml , p = 0.031) densities were higher in HCLD+. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD+ group (36% [114/287] vs. (19% [11/58]), ( p = 0.014), with SP and HI codetection (HCLD+: 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) being the most frequent. In 128 SP-positive participants (116 HCLD+, 12 HCLD-), 66% [85/128] of participants had non-PCV-13 serotypes detected. Serotypes 13 and 21 (9% [8/85] each) and PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) were more prevalent. Study participants with a history of previous tuberculosis treatment were more likely to carry SP or HI, while those who used ART for ≥2 years were less likely to carry HI and MC. Conclusion Children with HCLD+ were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.