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Childhood lung function following perinatal HIV infection and early antiretroviral therapy initiation: a cross-sectional study

Andre Gie, Julie Morrison, David Maree, Barbara Laughton, Sara H. Browne, Mark F. Cotton, Pierre Goussard, Steve Innes
ERJ Open Research 2022 8: 00691-2021; DOI: 10.1183/23120541.00691-2021
Andre Gie
1Dept of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
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  • For correspondence: agie@sun.ac.za
Julie Morrison
1Dept of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
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David Maree
2Dept of Medicine, Division of Pulmonology, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
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Barbara Laughton
1Dept of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
3Family Center for Research with Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa
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  • ORCID record for Barbara Laughton
Sara H. Browne
4Dept of Medicine, University of California San Diego, San Diego, CA, USA
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Mark F. Cotton
1Dept of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
3Family Center for Research with Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa
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Pierre Goussard
1Dept of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
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Steve Innes
1Dept of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
3Family Center for Research with Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa
5Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa
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  • Article
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Figures

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  • Supplementary Materials
  • FIGURE 1
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    FIGURE 1

    Participants recruited to perform pulmonary function tests and proportion who successfully completed spirometry, plethysmography and diffusing capacity testing.

  • FIGURE 2
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    FIGURE 2

    Age at antiretroviral therapy (ART) initiation in perinatally HIV-infected (HIV+) children. Data displayed as median (interquartile range).

  • FIGURE 3
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    FIGURE 3

    Spirometry (FEV1, FVC, FEV1/FVC) Z-scores of HIV-unexposed (HU), HIV-exposed-uninfected (HEU) and perinatally HIV-infected (HIV+) children. Z-scores calculated using Global Lung Initiative reference data and software. Normally distributed (mean±sd), compared with ordinary one-way ANOVA with Tukey post hoc multiple comparison test, non-normally distributed data (median (interquartile range)) compared with Kruskal–Wallis test and post hoc Dunn's correction for multiple comparisons. FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity.

  • FIGURE 4
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    FIGURE 4

    Plethysmography Z-scores for HIV-unexposed (HU), HIV-exposed-uninfected (HEU) and HIV+ children. Data displayed as mean±sd, comparison of groups with ordinary one-way ANOVA and Tukey post hoc multiple comparison test. Single data point of HEU Z-score for TLC and RV/TLC is not included in the figure as Z<−5 and >Z+7, respectively. TLC: total lung capacity; RV: residual volume, FRC: functional residual capacity. *p<0.05; **p<0.01; ****p<0.0001.

Tables

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  • TABLE 1

    Characteristics of participants

    HIV-unexposed (HU)HIV-exposed (HEU)HIV-infected (HIV+)HU versus HIV+
    (p-value)
    HEU versus HIV+
    (p-value)
    Subjects n90162142
    Age years8.8 (7.8–10.5)9.0 (7.9–10.6)8.4 (7.6–8.8)p=0.0004p<0.0001
    Ethnicity n (%)African 90 (100)African 147 (91)
    Mixed 15 (9)
    African 129 (91)
    Mixed 13 (9)
    Height cm128.3 (122.5–138.8)129.5 (124.1–139.0)123.8 (119.0–128.5)p<0.0001p<0.0001
    Height-for-age Z-score−0.56±1.1−0.53±1.09−0.87±1.00p=0.0848p=0.0187
    Weight kg27.75 (23.50–34.98)27.2 (23.9–33.2)24.3 (22.0–26.7)p<0.0001p<0.0001
    Weight-for-age Z-score−0.09±1.22−0.22±1.19−0.51±0.99p=0.0186p=0.0758
    Age at ART initiation weeks17.6 (8.0–36.7)
    Time interval years, first ART exposure to PFT7.65 (7.35–8.37)
    CD4 count at PFT (n=126) cells·mm−31065 (786–1298)
    HIV viral load at PFT (n=108) copies·mL−139 (19–302)
    HIV viral suppression at PFT (%)100 (92.6)

    Data are presented as mean±sd if normally distributed, median (interquartile range) if not normally distributed, unless otherwise stated. HIV viral suppression was defined as a HIV viral load <400 viral copies·mL−1. Compared with either one-way ANOVA with post hoc Tukey's multiple comparison test (normal distribution), Kruskal–Wallis with post hoc Dunn's multiple comparison test (not normally distributed) and Chi-square (categorical data). No statistically significant differences between HU and HEU. ART: antiretroviral therapy; PFT: pulmonary function test.

    • TABLE 2

      Successfully completed lung function tests of HIV-unexposed (HU), HIV-exposed-uninfected (HEU) and perinatally HIV-infected children on early ART (HIV+)

      HUHEUHIV+HU versus HIV+ (p-value)HEU versus HIV+ (p-value)
      Spirometry
       Subjects n76131120
       FEV1 absolute L1.380 (1.205–1.648)1.430 (1.200–1.710)1.250 (1.110–1.450)p=0.0057p=0.0001
       FEV1 Z-score−0.892±0.932−0.786±1.125−0.570±1.083p=0.1001p=0.2456
       FVC absolute L1.550 (1.32–1.813)1.570 (1.340–1.860)1.355 (1.195–1.598)p=0.0009p=0.0002
       FVC Z-score−0.894±0.898−0.953±1.196−0.669±1.207p=0.3695p=0.1199
       FEV1/FVC absolute0.89 (0.853–0.940)0.914 (0.863–0.962)0.909 (0.879–0.954)p=0.1771p>0.9999
       FEV1/FVC Z-score−0.031±1.2840.301±1.2050.1551±1.076p=0.5297p=0.5891
      Plethysmography
       Subjects n77128120
       Total lung capacity (TLC) L2.481±0.4872.467±0.5612.258±0.3524p=0.0041p=0.0018
       TLC Z-score−0.2194±1.050−0.406±1.1780.2906±0.9855p=0.0039p<0.0001
       Residual volume (RV) L0.8612±0.25840.8746±0.25370.8734±0.2257p=0.9373p=0.9992
       RV Z-score0.6125±0.76070.6251±0.71850.9497±0.6517p=0.0034p=0.001
       RV/TLC34.75±8.15335.56±9.21038.69±8.441p=0.0058p=0.0139
       RV/TLC Z-score1.399±0.83411.489±1.0591.733±0.8190p=0.0371p=0.0995
       Functional residual capacity (FRC) L1.28 (1.13–1.55)1.33 (1.15–1.59)1.18 (1.06–1.36)p=0.0135p=0.0001
       FRC Z-score0.3676±0.93910.4456±0.88290.7156±0.8926p=0.0234p=0.0504
       Vital capacity (VCPLETH) L1.540 (1.285–1.860)1.530 (1.290–1.825)1.380 (1.195–1.598)p=0.0011p=0.0008
       VCPLETH Z-score−2.179±0.8135−2.281±1.061−2.157±1.077p=0.9884p=0.6037
      Diffusing capacity
       Subjects n6210598
       DLCO14.75 (13.22–16.87)14.77 (12.69–17.01)13.93 (12.46–16.09)p=0.1802p=0.2837
       DLCO Z-score0.231 (−0.25–0.76)0.176 (−0.38–0.82)0.50 (0.01–1.28)p=0.0375p=0.0026
       Alveolar volume (VA) L2.370 (2.068–2.800)2.380 (2.095–2.790)2.11 (1.938–2.315)p=0.0005p<0.0001
       VA Z-score−0.44 (−1.15–0.18)−0.34 (−1.0–0.52)−0.19 (−0.68–0.36)p=0.1480p>0.9999
       DLCO/VA6.400 (5.788–6.783)6.010 (5.395–6.680)6.565 (6.005–7.230)p=0.1564p<0.0001

      Data are presented as mean±sd if normally distributed, median (interquartile range) if not normally distributed, unless otherwise stated. No statistically significant differences between HU and HEU. ART: antiretroviral therapy; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide.

      Supplementary Materials

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        Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

        Supplementary figure 00691-2021.SUPPLEMENT

        Supplementary methods 00691-2021.SUPPL_METHODS

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      Childhood lung function following perinatal HIV infection and early antiretroviral therapy initiation: a cross-sectional study
      Andre Gie, Julie Morrison, David Maree, Barbara Laughton, Sara H. Browne, Mark F. Cotton, Pierre Goussard, Steve Innes
      ERJ Open Research Jan 2022, 8 (1) 00691-2021; DOI: 10.1183/23120541.00691-2021

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      Childhood lung function following perinatal HIV infection and early antiretroviral therapy initiation: a cross-sectional study
      Andre Gie, Julie Morrison, David Maree, Barbara Laughton, Sara H. Browne, Mark F. Cotton, Pierre Goussard, Steve Innes
      ERJ Open Research Jan 2022, 8 (1) 00691-2021; DOI: 10.1183/23120541.00691-2021
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