Outcomes of HIV-exposed infected and HIV-exposed uninfected children admitted to two paediatric intensive care units in South Africa: A retrospective analytical cohort study

Main Article Content

M van der Merwe
J B Sempa
M A Pienaar

Abstract





Background. Reduced vertical transmission of HIV has led to an increased proportion of HIV-exposed uninfected children (HEU) in South Africa. Increased infective morbidity and mortality creates a need to better understand outcomes and morbidity in this population.


Objectives. To describe and compare critical care outcomes in terms of survival and disease severity between HIV-unexposed children (HUU), HIV-exposed infected children (HEI) and HEU.


Methods. A retrospective analytical cohort study was carried out from 1 January 2017 to 31 December 2021. Paediatric intensive care unit admissions of children aged 1 month - 5 years were included. Outcomes for HEU and HEI were compared with those of HUU, with a significance threshold set at p=0.05. Multivariate logistic regression analysis was conducted.


Results. Of 1 015 children, 633 (62.4%) were HUU, 318 (31.3%) were HEU and 64 (6.3%) were HEI. Mortality was higher in HEU (15.8%; p=0.1) and HEI (17.2%; p=0.4) compared with HUU (11.4%), but this was not statistically significant. HEU and HEI were younger (p<0.001) and more frequently underweight (p<0.001). HEU (and HEI) had an increased risk of acute kidney injury (AKI) (odds ratio 1.19; 95% confidence interval 1.07 - 1.81; p=0.014) and a lower minimum estimated glomerular filtration rate (p<0.001) compared with HUU. Septic shock was more frequent in HEU (28.6%; p=0.001) and HEI (43.8%; p<0.001) compared with HUU (20.1%). HEI had more frequent mechanical ventilation (p=0.003), more prolonged mechanical ventilation (p<0.001) and lower admission haemoglobin concentrations (p<0.001) than HUU.


Conclusion. Compared with HUU, both HEU and HEI demonstrated a trend towards increased mortality, but this was not statistically significant. HEU and HEI experienced increased AKI and other morbidity.





Article Details

Section

Research Articles

Author Biographies

M van der Merwe, Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa

MBChB, Registrar, Department of Paediatrics and Child Health, University of the Free State

J B Sempa, Department of Biostatistics, School of Biomedical Sciences, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa

PhD (Epi), Senior Lecturer, Department of Biostatistics, University of the Free State

M A Pienaar, Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa

FCPaed(SA), Cert. Crit. Care (SA) Paed, PhD. Associate Professor, Department of Paediatrics and Child Health, University of the Free State. 

How to Cite

Outcomes of HIV-exposed infected and HIV-exposed uninfected children admitted to two paediatric intensive care units in South Africa: A retrospective analytical cohort study. (2025). Southern African Journal of Critical Care, 41(2), e1825. https://doi.org/10.7196/SAJCC.2025.v412.1825

References

1. Wessels J, Sherman G, Bamford L, et al. The updated South African National Guideline for the Prevention of Mother to Child Transmission of Communicable Infections (2019). South Afr J HIV Med 2020;21(1):1079. https://doi.org/10.4102/sajhivmed.v21i1.1079

2. Slogrove AL, Goetghebuer T, Cotton MF, Singer J, Bettinger JA. Pattern of infectious morbidity in HIV-exposed uninfected infants and children. Front Immunol 2016;7:1-8. https://doi. org/10.3389/fimmu.2016.00164

3. Slogrove AL. It is a question of equity: Time to talk about children who are HIV-exposed and ‘HIV-free’. J Int AIDS Soc 2021;24(11):e25850. https://doi.org/10.1002/jia2.25850

4. Slogrove AL, Powis KM, Johnson LF, Stover J, Mahy M. Estimates of the global population of children who are HIV-exposed and uninfected, 2000-18: A modelling study. Lancet Glob Health 2020;8(1):e67-e75. https://doi.org/10.1016/S2214-109X(19)30448-6

5. Hall K. Statistics on children in South Africa: Demography. Children Count, 2023. http://www. childrencount.uct.ac.za/indicator.php?domain=1&indicator=1 (accessed 9 November 2013).

6. Brennan AT, Bonawitz R, Gill CJ, et al. A meta-analysis assessing diarrhea and pneumonia in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children. J Acquir Immune Defic Syndr 2019;82(1):1-8. https://doi.org/10.1097/QAI.0000000000002097

7. Arikawa S, Rollins N, Newell ML, Becquet R. Mortality risk and associated factors in HIV- exposed, uninfected children. Trop Med Int Health 2016;21(6):720-734. https://doi.org/10.1111/ tmi.12695

8. Rollins NC, Ndirangu J, Bland RM, Coutsoudis A, Coovadia HM, Newell ML. Exclusive breastfeeding, diarrhoeal morbidity and all-cause mortality in infants of HIV-infected and HIV uninfected mothers: An intervention cohort study in KwaZulu Natal, South Africa. PLoS ONE 2013;8(12):e81307. https://doi.org/10.1371/journal.pone.0081307

9. Slogrove A, Reikie B, Naidoo S, et al. HIV-exposed uninfected infants are at increased risk for severe infections in the first year of life. J Trop Pediatr 2012;58(6):505-508. https://doi. org/10.1093/tropej/fms019

10. Kelly MS, Wirth KE, Steenhoff AP, et al. Treatment failures and excess mortality among HIV- exposed, uninfected children with pneumonia. J Pediatric Infect Dis Soc 2015;4(4):e117-e126. https://doi.org/10.1093/jpids/piu092

11. Afran L, Knight MG, Ndauti E, Heyderman RS, Rowland-Jones SL. HIV-exposed uninfected children: A growing population with a vulnerable immune system? Clin Exp Immunol 2014;176(1):11-22. https://doi.org/10.1111/cei.12251

12. Keeling KH, Price J, Naidoo KD. HIV exposure and its association with paediatric ICU outcomes in children admitted with severe pneumonia at Chris Hani Baragwanath Academic Hospital, South Africa. S Afr J Child Health 2022;16(3):130-133. https://doi.org/10.7196/SAJCH.2022. v16i3.1890

13. Whitehead K, Ballot DE. A retrospective observational study of the impact of HIV status on the outcome of paediatric intensive care unit admissions at a tertiary hospital in South Africa (2015- 2019). Pediatr Rep 2023;15(4):679-690. https://doi.org/10.3390/pediatric15040061

14. Joint United Nations Programme on HIV/AIDS (UNAIDS). The path that ends AIDS: UNAIDS Global AIDS Update 2023. https://www.unaids.org/en/resources/documents/2023/global-aids- update-2023 (accessed 30 June 2025).

15. Straney L, Clements A, Parslow RC, et al. Paediatric Index of Mortality 3: An updated model for predicting mortality in pediatric intensive care. Pediatr Crit Care Med 2013;14(7):673-681. https://doi.org/10.1097/PCC.0b013e31829760cf

16. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012;2(1):1-138. https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-AKI-Guideline-English.pdf (accessed 24 March 2025).

17. Mopeli RK, Ballot DE, White DA. An audit of primary medical conditions in children admitted to the paediatric intensive care unit of Charlotte Maxeke Johannesburg Academic Hospital. S Afr J Child Health 2016;10(4):221-226. https://doi.org/10.7196/SAJCH.2016.v10i4.1187

18. Hutton HK, Zar HJ, Argent AC. Clinical features and outcome of children with severe lower respiratory tract infection admitted to a pediatric intensive care unit in South Africa. J Trop Pediatr 2019;65(1):46-54. https://doi.org/10.1093/tropej/fmy010

19. Le Roux SM, Abrams EJ, Nguyen K, Myer L. Clinical outcomes of HIV-exposed, HIV-uninfected children in sub-Saharan Africa. Trop Med Int Health 2016;21(7):829-845. https://doi.org/10.1111/ tmi.12716

20. Li H, Yuan S, Liao M, et al. Effects of HIV exposure on anemia and vitamin D nutritional status in children aged 6-24 months: A hospital-based cross-sectional study. Sci Rep 2025;15:2839. https:// doi.org/10.1038/s41598-025-87101-9

21. Younous S, Nadifiyine D, Yassine A, et al. High rates of nosocomial infections and antimicrobial resistance in a Moroccan pediatric intensive care unit: A cause for alarm. IJID Reg 2024;13:100423. https://doi.org/10.1016/j.ijregi.2024.100423

22. De Zan F, Amigoni A, Pozzato R, Pettenazzo A, Murer L, Vidal E. Acute kidney injury in critically ill children: A retrospective analysis of risk factors. Blood Purif 2020;49(1-2):1-7. https://doi. org/10.1159/000502081

23. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL; AWARE Investigators. Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med 2017;376(1):11-20. https:// doi.org/10.1056/NEJMoa1611391

24. Sanchez-Pinto LN, Bennett TD, Dewitt PE, et al. Development and validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock. JAMA 2024;331(8):675-686. https://doi. org/10.1001/jama.2024.0196

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