Abstract:
BACKGROUND: HIV-associated chronic lung disease (CLD) is common among children living with HIV (CLWH) in sub-
Saharan Africa, including those on antiretroviral therapy (ART). However, the pathogenesis of CLD and its possible
association with microbial determinants remain poorly understood. We investigated the prevalence, and antibiotic
susceptibility of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and
Moraxella catarrhalis (MC) among CLWH (established on ART) who had CLD (CLD+), or not (CLD-) in Zimbabwe and
Malawi.
METHODS: Nasopharyngeal swabs (NP) and sputa were collected from CLD+ CLWH (defined as forced-expiratory
volume per second z-score < − 1 without reversibility post-bronchodilation with salbutamol), at enrolment as part of
a randomised, placebo-controlled trial of azithromycin (BREATHE trial - NCT02426112), and from age- and sexmatched
CLD- CLWH. Samples were cultured, and antibiotic susceptibility testing was conducted using disk
diffusion. Risk factors for bacterial carriage were identified using questionnaires and analysed using multivariate
logistic regression.
RESULTS: A total of 410 participants (336 CLD+, 74 CLD-) were enrolled (median age, 15 years [IQR = 13–18]). SP and
MC carriage in NP were higher in CLD+ than in CLD- children: 46% (154/336) vs. 26% (19/74), p = 0.008; and 14%
(49/336) vs. 3% (2/74), p = 0.012, respectively. SP isolates from the NP of CLD+ children were more likely to be nonsusceptible
to penicillin than those from CLD- children (36% [53/144] vs 11% [2/18], p = 0.036). Methicillin-resistant
SA was uncommon [4% (7/195)]. In multivariate analysis, key factors associated with NP bacterial carriage included
having CLD (SP: adjusted odds ratio (aOR) 2 [95% CI 1.1–3.9]), younger age (SP: aOR 3.2 [1.8–5.8]), viral load
suppression (SP: aOR 0.6 [0.4–1.0], SA: 0.5 [0.3–0.9]), stunting (SP: aOR 1.6 [1.1–2.6]) and male sex (SA: aOR 1.7 [1.0– 2.9]). Sputum bacterial carriage was similar in both groups (50%) and was associated with Zimbabwean site (SP:
aOR 3.1 [1.4–7.3], SA: 2.1 [1.1–4.2]), being on ART for a longer period (SP: aOR 0.3 [0.1–0.8]), and hot compared to
rainy season (SP: aOR 2.3 [1.2–4.4]).
CONCLUSIONS: CLD+ CLWH were more likely to be colonised by MC and SP, including penicillin-non-susceptible SP
strains, than CLD- CLWH. The role of these bacteria in CLD pathogenesis, including the risk of acute exacerbations,
should be further studied.
