Impact of HIV and antiretroviral drug exposure on lung growth and function over 2 years in an African Birth Cohort.

Diane M Gray,Carvern Jacobs,Lauren Mcmillan,Graham L Hall,Jacob A.M Stadler,Catherine J Wedderburn,Heather J Zar,Rae P Macginty

doi:10.1097/qad.0000000000002444

Abstract

To assess the impact of HIV and antiretroviral exposure without infection on lung growth and function over the first 2 years of life. Prospective observational study of an African birth cohort, Drakenstein Child Health Study. Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received antiretroviral therapy (ART) as per local guidelines. The association between HIV and antiretroviral exposure with lung function was assessed using mixed effects modelling. Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume compared with HIV-unexposed infants (1.13 ml, confidence interval: 0.02-2.23, P = 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, confidence interval 0.00-0.34, P = 0.046). First-line ART initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (-2.7 ml, -5.31 to -0.10, P = 0.042), and low maternal CD4 cell counts associated with lower infant tidal over 2 years (-11.1 ml, -18.58-3.58, P = 0.004). HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. These data highlight the importance of ongoing surveillance of respiratory health in HEU children.

Highlights

Respiratory disease is the leading cause of death outside the neonatal period in children under 5 years worldwide [1] and despite progress towards the SustainableDevelopment Goals, many countries fall far behind the global under-5 mortality targets
Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years
First-line antiretroviral therapy (ART) initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (À2.7 ml, À5.31 to À0.10, P 1⁄4 0.042), and low maternal CD4þ cell counts associated with lower infant tidal over 2 years (À11.1 ml, À18.58–3.58, P 1⁄4 0.004)

Summary

Introduction

Development Goals, many countries fall far behind the global under-5 mortality targets This is evident in sub-Saharan Africa (SSA) which has the highest under-5 mortality rate globally, and where children have a 15-fold higher likelihood of dying before aDepartment of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital and SA-MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa, bDepartment of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK, and cTelethon Kids Institute and School of Physiotherapy and Exercise Science, Curtin University, Perth, Western Australia, Australia. PhD, MD, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital and SA-MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.

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Conclusion