Neurocognitive function among HIV-infected children on protease inhibitor -based versus non-protease inhibitor based antiretroviral therapy in Uganda: a pilot study

Damalie Nalwanga, Victor Musiime, Paul Bangirana, Erika Phelps Nishiguchi, Andrew Kiggwe, Titus Ssesanga, John M. Ssenkusu, Philippa Musoke, Sarah E. Cusick

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BACKGROUND: HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children's neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART.

METHODS: We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5-12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel's method was used to adjust for multiple testing.

RESULTS: We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03).

CONCLUSIONS: We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.

Original languageEnglish (US)
Article number198
JournalBMC Pediatrics
Issue number1
StatePublished - Dec 2021

Bibliographical note

Funding Information:
We acknowledge the Joint Clinical Research Centre (JCRC) Paediatric clinic for their support during enrolment, Irene Akello who carried out the neurocognitive tests, Dr. Michael Boivin for donating TOVA testing equipment to the study, Global Health Uganda (GHU) for administrative and technical support for the trial and the children and parents/guardians who agreed to participate in the research.

Funding Information:
Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under grant #D43TW009345 awarded to the Northern Pacific Global Health Fellows Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.(7,19).

Funding Information:
The study was conducted at the Joint Clinical Research Centre (JCRC), Kampala, Uganda. It is located approximately 10 km outside Kampala, the capital city of Uganda. JCRC has led the treatment of HIV/AIDS and opportunistic infections in Uganda. It has served over 200,000 clients on first, second and third line ART countrywide. The JCRC paediatric clinic provides longitudinal clinical care and psychosocial support to over 1000 children living with HIV. JCRC also conducts research in several fields including HIV vaccines, ART, opportunistic infections, public health and social behaviours []. JCRC is funded through research and implementation grants, institutional research collaborations, internally generated revenue, and support from the Uganda Ministry of Health.

Publisher Copyright:
© 2021, The Author(s).


  • ART
  • Children
  • HIV
  • Neurocognitive function
  • Prospective Studies
  • Humans
  • Child, Preschool
  • Anti-HIV Agents/therapeutic use
  • Protease Inhibitors/therapeutic use
  • Viral Load
  • HIV Infections/drug therapy
  • Pilot Projects
  • Quality of Life
  • Adult
  • Uganda
  • Child

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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