Chronic lung disease in HIV-infected children established on antiretroviral therapy.
Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group.



A cross-sectional study in Zimbabwe of HIV-infected children aged 6-16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area.



Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4 cell count, HIV viral load and sputum culture for tuberculosis were performed.



A total of 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8-7.5) and 6.1 (interquartile range 3.6-8.4) years, respectively. Median CD4 cell count was 726 cells/μl, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n = 1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P < 0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889 m, respectively, P < 0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P = 0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P = 0.025). No participant tested positive for Mycobacterium tuberculosis.



In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required.
aLiverpool School of Tropical Medicine, Liverpool, UK bBiomedical Research and Training Institute, Harare, Zimbabwe cUniversity of California, San Francisco, San Francisco, California, USA dUniversity of Zimbabwe, Harare, Zimbabwe eUniversity of Oxford, Oxford fLondon School of Hygiene and Tropical Medicine gRoyal Free Hospital, London, UK.
Jamie
J
Rylance
Grace
G
Mchugh
John
J
Metcalfe
Hilda
H
Mujuru
Kusum
K
Nathoo
Stephanie
S
Wilmore
Sarah
S
Rowland-Jones
Edith
E
Majonga
Katharina
K
Kranzer
Rashida A
RA
Ferrand
D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002908:Chronic Disease / Q000453:epidemiology; D003430:Cross-Sectional Studies; D015444:Exercise; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008171:Lung Diseases / Q000453:epidemiology* / Q000473:pathology*; D008297:Male; D013147:Spirometry; D011795:Surveys and Questionnaires; D019562:Viral Load; D015030:Zimbabwe
D044966:Anti-Retroviral Agents
Thorax. 2015 Sep;70(9):840-6
26060256
Thorax. 1992 Dec;47(12):1019-24
1494764
Clin Radiol. 2011 Mar;66(3):257-63
21295205
Pediatr Pulmonol. 2003 Feb;35(2):133-8
12526075
Lancet Infect Dis. 2014 Sep;14(9):794-5
25164190
Bull World Health Organ. 2010 Jun;88(6):428-34
20539856
N Engl J Med. 2015 Aug 27;373(9):795-807
26192873
N Engl J Med. 2015 Aug 27;373(9):808-22
26193126
Am J Respir Crit Care Med. 2013 Sep 15;188(6):647-56
23898922
J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):275-281
27171738
J Pediatric Infect Dis Soc. 2016 Jun;5(2):161-9
26407277
HIV Med. 2016 Feb;17 (2):89-105
26452565
Clin Infect Dis. 2012 Jul;55(1):145-52
22474177
AIDS. 2011 Mar 13;25(5):717-20
21252630
Am J Respir Crit Care Med. 2007 Jul 15;176(2):174-80
17463419
Pediatr Pulmonol. 1997 Dec;24(6):406-14
9448232
Clin Infect Dis. 2013 Feb;56(4):576-82
23097588
Eur Respir J. 2005 Aug;26(2):319-38
16055882
Eur Respir J. 2012 Dec;40(6):1324-43
22743675
PLoS One. 2013 Nov 01;8(11):e78926
24223865
Jpn J Radiol. 2011 Oct;29(8):554-62
21927997
J Infect Dis. 2009 Oct 15;200(8):1212-5
19728788
JAMA. 2006 Jul 19;296(3):292-300
16849662
J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):420-7
26914911
J Am Coll Cardiol. 2001 Jan;37(1):153-6
11153730
Ann Am Thorac Soc. 2014 Jul;11(6):915-24
24960156
Pediatrics. 2011 Feb;127(2):e423-41
21262891
Pediatr Pulmonol. 2008 Jan;43(1):1-10
18041077
J Int AIDS Soc. 2013 Jun 18;16:18633
23782483
AIDS. 1998 Jul 9;12(10):1185-93
9677168
Arch Dis Child. 1997 Apr;76(4):334-6
9166026
Respiration. 2013;86(1):76-85
23652030
Curr Opin Infect Dis. 2016 Feb;29(1):31-8
26555039
Int J Tuberc Lung Dis. 2012 Jan;16(1):114-9
22236856