Respiratory Complications in Children and Adolescents with Human Immunodeficiency Virus

Githinji, Leah; Zar, Heather J.

doi:10.1016/j.pcl.2020.09.016

Cited by 4 publications

(14 citation statements)

References 62 publications

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“…Of these 1.7 million CLWH, only 59% have been initiated on highly active antiretroviral therapy ( 42 ). The lungs are a primary target for infections in CLWH, with recurrent and severe LRTI, increased risk of TB infection, infection with opportunistic organisms, as well as immune dysregulation by HIV causing inflammation and an altered lung microbiome, all potential precursors of BE ( 21 , 27 , 43 – 46 ). In older children and adolescents with perinatally-acquired HIV in Zimbabwe, chronic lung disease was common (86%); between 33% (28/84) and 43% (24/56) had confirmed BE on high-resolution CT ( 15 , 16 ).…”

Section: Etiologymentioning

confidence: 99%

Bronchiectasis in African children: Challenges and barriers to care

et al. 2022

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Bronchiectasis (BE) is a chronic condition affecting the bronchial tree. It is characterized by the dilatation of large and medium-sized airways, secondary to damage of the underlying bronchial wall structural elements and accompanied by the clinical picture of recurrent or persistent cough. Despite an increased awareness of childhood BE, there is still a paucity of data on the epidemiology, pathophysiological phenotypes, diagnosis, management, and outcomes in Africa where the prevalence is mostly unmeasured, and likely to be higher than high-income countries. Diagnostic pathways and management principles have largely been extrapolated from approaches in adults and children in high-income countries or from data in children with cystic fibrosis. Here we provide an overview of pediatric BE in Africa, highlighting risk factors, diagnostic and management challenges, need for a global approach to addressing key research gaps, and recommendations for practitioners working in Africa.

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Section: Etiologymentioning

confidence: 99%

Bronchiectasis in African children: Challenges and barriers to care

et al. 2022

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“…Previous studies report chronic respiratory symptoms to be common in CAHIV, especially in those not established on ART or those who had delayed initiation [ 2 , 15 – 17 , 27 , 28 ]. We found that most participants with cough also had increased sputum or chest congestion, as also seen in other studies [ 15 , 16 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…The identification of factors associated with CLD may help inform interventions for improved prevention and care [ 2 , 10 ]. CLD in our cohort was associated with late initiation of ART and high viral load as previously described [ 2 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence, clinical presentation and factors associated with chronic lung disease among children and adolescents living with HIV in Kenya

Maleche-Obimbo,

Attia,

Were

et al. 2023

PLoS ONE

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Introduction Children and adolescents with HIV (CAHIV) may experience recurrent and severe respiratory disease and are at risk of residual lung sequelae, and long-term morbidity from chronically damaged lungs. With improved survival due to increased access to effective antiretroviral therapy there is an increasing population of CAHIV who require optimal life-long care. Chronic lung disease in CAHIV is an under-recognised problem in African settings. We sought to determine the prevalence, clinical presentation and factors associated with chronic lung disease (CLD) among CAHIV in Kenya. Methods CAHIV aged ≤19 years in care at a public hospital in Nairobi were enrolled into a longitudinal cohort study. Sociodemographic and clinical information were obtained through interview, medical record review, physical examination and six-minute walk test. CD4 counts and viral load were determined. Enrolment data was analysed to determine baseline sociodemographic and clinical characteristics. Prevalence of CLD defined as presence of ≥2 respiratory symptoms or signs at enrolment was computed. Logistic regression analysis was performed to evaluate for association between various factors and presence or absence of CLD. Results We enrolled 320 CAHIV of median age 13 (IQR 10–16) years, 80 (25%) were <10 years, 46% were female, 31% lived in a one-room house and 51% used polluting cooking fuel. Antiretroviral therapy (ART) was initiated after age five years in 56%, 43% had prior pneumonia or tuberculosis, 11% had low CD4 count and 79% were virologically suppressed. Common respiratory symptoms and signs were exertional breathlessness (40%), chronic cough (23%), chest problems in the preceding year (24%), tachypnoea (52%), finger clubbing (6%), exercise limitation (59%) and oxygen desaturation during exercise (7%). CLD was present in 82 (26%) participants, and adding the six-minute walk distance <70% of predicted (exercise limitation) identified an additional 28 (9%) CAHIV with CLD. CLD was more common among older teenagers (odds ratio (OR) 1.95), those who had prior TB or pneumonia (OR 2.04), delayed initiation of ART (OR 2.60), cotrimoxazole prophylaxis (OR 3.35) or TB preventive therapy (OR 2.81). CLD was associated with viraemia (OR 2.7), lower quality of life (OR 12.7), small houses (OR 2.05), caregiver having fewer years of education (OR 2.46), outdoor pollution exposure (OR 3.31) and lower use of polluting cooking fuel indoors (OR 0.26). Adjusted analysis revealed CLD to be associated with prior tuberculosis or pneumonia (adjusted OR (aOR) [95%CI] 2.15 [1.18–3.91]), small house (aOR 1.95 [1.02–3.73]), lower use of polluting cooking fuel (aOR 0.35 [0.13–0.94]) and negative impact on health-related quality of life (aOR 6.91 [3.66–13.03]). Conclusions CLD is highly prevalent across the age spectrum of CAHIV, and most are symptomatic with cough or exertional breathlessness. CLD is associated with prior tuberculosis or pneumonia, socio-environmental factors, and lower quality of life. Structured interventions are needed to provide optimal care specific to their needs.

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Section: Introductionmentioning

confidence: 99%

“…HIV-associated chronic lung disease (HCLD) is the most common chronic complication of HIV and accounts for more than 50% of all HIV-related mortality [ 1 ]. HCLD includes tuberculosis, chronic aspiration pneumonia and bronchiectasis [ 1 ]. Recently, in sub-Saharan Africa (Zimbabwe [ 2 , 3 ], Malawi [ 4 ], South Africa [ 5 , 6 ]), a novel HCLD phenotype, obliterative bronchiolitis, was detected at high prevalence (> 30%) among older children and adolescents living with HIV [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Sputum bacterial load and bacterial composition correlate with lung function and are altered by long-term azithromycin treatment in children with HIV-associated chronic lung disease

Abotsi

Dube²,

Rehman³

et al. 2023

Microbiome

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Background Long-term azithromycin (AZM) treatment reduces the frequency of acute respiratory exacerbation in children and adolescents with HIV-associated chronic lung disease (HCLD). However, the impact of this treatment on the respiratory bacteriome is unknown. Method African children with HCLD (defined as forced expiratory volume in 1 s z-score (FEV1z) less than − 1.0 with no reversibility) were enrolled in a placebo-controlled trial of once-weekly AZM given for 48-weeks (BREATHE trial). Sputum samples were collected at baseline, 48 weeks (end of treatment) and 72 weeks (6 months post-intervention in participants who reached this timepoint before trial conclusion). Sputum bacterial load and bacteriome profiles were determined using 16S rRNA gene qPCR and V4 region amplicon sequencing, respectively. The primary outcomes were within-participant and within-arm (AZM vs placebo) changes in the sputum bacteriome measured across baseline, 48 weeks and 72 weeks. Associations between clinical or socio-demographic factors and bacteriome profiles were also assessed using linear regression. Results In total, 347 participants (median age: 15.3 years, interquartile range [12.7–17.7]) were enrolled and randomised to AZM (173) or placebo (174). After 48 weeks, participants in the AZM arm had reduced sputum bacterial load vs placebo arm (16S rRNA copies/µl in log10, mean difference and 95% confidence interval [CI] of AZM vs placebo − 0.54 [− 0.71; − 0.36]). Shannon alpha diversity remained stable in the AZM arm but declined in the placebo arm between baseline and 48 weeks (3.03 vs. 2.80, p = 0.04, Wilcoxon paired test). Bacterial community structure changed in the AZM arm at 48 weeks compared with baseline (PERMANOVA test p = 0.003) but resolved at 72 weeks. The relative abundances of genera previously associated with HCLD decreased in the AZM arm at 48 weeks compared with baseline, including Haemophilus (17.9% vs. 25.8%, p < 0.05, ANCOM ω = 32) and Moraxella (1% vs. 1.9%, p < 0.05, ANCOM ω = 47). This reduction was sustained at 72 weeks relative to baseline. Lung function (FEV1z) was negatively associated with bacterial load (coefficient, [CI]: − 0.09 [− 0.16; − 0.02]) and positively associated with Shannon diversity (0.19 [0.12; 0.27]). The relative abundance of Neisseria (coefficient, [standard error]: (2.85, [0.7], q = 0.01), and Haemophilus (− 6.1, [1.2], q < 0.001) were positively and negatively associated with FEV1z, respectively. An increase in the relative abundance of Streptococcus from baseline to 48 weeks was associated with improvement in FEV1z (3.2 [1.11], q = 0.01) whilst an increase in Moraxella was associated with decline in FEV1z (-2.74 [0.74], q = 0.002). Conclusions AZM treatment preserved sputum bacterial diversity and reduced the relative abundances of the HCLD-associated genera Haemophilus and Moraxella. These bacteriological effects were associated with improvement in lung function and may account for reduced respiratory exacerbations associated with AZM treatment of children with HCLD.

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Respiratory Complications in Children and Adolescents with Human Immunodeficiency Virus

Cited by 4 publications

References 62 publications

Bronchiectasis in African children: Challenges and barriers to care

Bronchiectasis in African children: Challenges and barriers to care

Prevalence, clinical presentation and factors associated with chronic lung disease among children and adolescents living with HIV in Kenya

Sputum bacterial load and bacterial composition correlate with lung function and are altered by long-term azithromycin treatment in children with HIV-associated chronic lung disease

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