Lung function tracking in children with perinatally acquired HIV following early antiretroviral therapy initiation
André Gie1, Claire Davies2, Florin Vaida3
1Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa agie@sun.ac.za.
Insights
Early antiretroviral therapy (ART) in children with perinatal HIV infection (CHIV) preserves lung function, though small airway disease remains a concern. Perinatal HIV exposure without infection (CHEU) did not impact lung function trajectories.
Area of Science:
- Pediatric pulmonology
- Infectious diseases
- Public health
Background:
- Lung disease is a common complication in children with perinatal HIV infection (CHIV) and exposure without infection (CHEU), leading to reduced lung function.
- While early antiretroviral therapy (ART) improves survival and other outcomes in CHIV, its specific benefit on lung function remains unclear.
Purpose of the Study:
- To evaluate the impact of early ART initiation on lung function trajectories in children with CHIV compared to HIV-unexposed children (CHU).
- To assess the effect of perinatal HIV exposure without infection (CHEU) on childhood lung function trajectories compared to CHU.
Main Methods:
- Prospective pulmonary function testing (PFT) including spirometry, plethysmography, and diffusing capacity was conducted in cohorts of CHIV (ART initiated at median 4.0 months), CHEU, and CHU from 2013 to 2020.
- Linear mixed-effects models with multiple imputation were used to determine lung function trajectories, comparing CHIV to CHU and CHEU to CHU, while accounting for potential confounders.
Main Results:
- Spirometry outcomes (FEV1, FVC, FEV1/FVC) were similar across all groups.
- Children with CHIV showed a significantly greater mean residual volume (RV) z-score compared to CHU (17% increase, p=0.042), suggesting potential small airway abnormalities.
- No significant differences were observed in total lung capacity (TLC) or RV/TLC z-scores between groups; alveolar volume (VA) differed by sex in HIV-exposed groups.
Conclusions:
- Early ART initiation in CHIV appears to mitigate lung function decline, offering lasting benefits throughout childhood, but concerns for small airway disease persist.
- Perinatal HIV exposure without infection (CHEU) does not seem to disrupt the normal trajectory of lung function development in children.
Introduction:
Lung disease remains a frequent complication in children with perinatal HIV infection (CHIV) and exposure without infection (CHEU), resulting in diminished lung function. In CHIV, early antiretroviral therapy (ART) initiation improves survival and extrapulmonary outcomes. However, it is unknown if there is benefit to lung function.
Methods:
Cohorts of CHIV (ART initiated at median 4.0 months), CHEU and HIV-unexposed children (CHU) prospectively performed pulmonary function testing (PFT) consisting of spirometry, plethysmography and diffusing capacity from 2013 to 2020. We determined lung function trajectories for PFT outcomes comparing CHIV to CHU and CHEU to CHU, using linear mixed effects models with multiple imputation. Potential confounders included sex, age, height, weight, body mass index z-score, urine cotinine and Tanner stage.
Results:
328 participants (122 CHIV, 126 CHEU, 80 CHU) performed PFT (ages 6.6-15.6 years). Spirometry (forced expiratory volume in 1 s, FEV1, forced vital capacity (FVC), FEV1/FVC) outcomes were similar between groups. In plethysmography, the mean residual volume (RV) z-score was 17% greater in CHIV than CHU (95% CI 1% to 33%, p=0.042). There was no difference in total lung capacity (TLC) or RV/TLC z-scores between groups. Diffusing capacity for carbon monoxide was similar in all groups, while alveolar volume (VA) differed between HIV groups by sex.
Conclusion:
Our study indicates that early ART initiation can mitigate the loss of lung function in CHIV with lasting benefit through childhood; however, there remains concern of small airway disease. CHEU does not appear to disrupt childhood lung function trajectory.
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