The Eswatini Study on Neurocognitive Performance in Adolescents Living With HIV

NCT07165639 | Not Yet Recruiting

• 1 other identifier: EHHRRB 049/2025
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study explores the link between inflammatory biomarkers and neurocognitive performance in adolescents living with HIV (ALHIV) in Eswatini. Persistent HIV infection during adolescence has been associated with ongoing systemic inflammation and subsequent neurocognitive dysfunction. However, the exact nature of this relationship is not well-defined, especially in resource-limited settings where epidemiological and mechanistic data are scarce. objectives

• To determine the prevalence of cognitive impairment among a sample of adolescents living with HIV, compared to HIV-negative adolescents in Eswatini
• To assess the relationship between neurocognitive performance and current viral load status in adolescent living with HIV (ALHIV).
• To examine the association between inflammation biomarkers and viral load suppression status in ALHIV.
• To investigate whether adolescents with HIV experiencing neurocognitive decline exhibit a high inflammatory status. A case-control design will be employed, involving 80 adolescents aged 13-19 years: 50 who are HIV-positive and 30 HIV-negative controls. Participants will be recruited from Baylor Manzini and Mbabane, as well as Raleigh Fitkin Memorial Hospital. Neurocognitive function will be evaluated using the Symbol Digit Modalities Test, focusing on areas such as processing speed, motor coordination, attention, and visual scanning. Blood samples will be collected to measure key inflammatory biomarkers, including C-reactive protein (CRP), soluble CD14 (sCD14), lipopolysaccharide (LPS), soluble CD163 (sCD163), and monocyte chemoattractant protein-1 (MCP-1). Sociodemographic and clinical data will be gathered through questionnaires and medical record reviews. Primary outcomes will include neurocognitive performance scores, while secondary outcomes will involve biomarker levels and their correlation with cognitive function. Multivariate regression models will assess associations, adjusting for confounders such as age, sex, education, and HIV disease severity. Structural equation modeling will be used to explore potential mediators in the inflammation-cognition pathway.

Conditions

HIV (Human Immunodeficiency Virus)

Keywords

adolescent; Human Immunodeficiency Virus; inflammation biomarkers; neurocognitive performance; Eswatini

Outcome Measures

Primary Outcomes (1)

• Neurocognitive performance

  The Symbol Digit Modalities Test (SDMT) assesses neurocognitive performance by evaluating processing speed, attention, and visual-motor coordination. Participants are required to use a key to match symbols with digits as swiftly as possible within a 90-second timeframe, with the score indicating the number of correct matches. Z-scores, which typically range from -3.0 to +3.0, are employed to interpret results in relation to age and population norms. A score of 0 denotes average performance, while scores between +1 and +3 suggest above-average cognitive abilities. Conversely, scores from -1 to -1.5 may indicate mild impairment, and those below -1.5 often highlight clinically significant deficits, particularly in adolescents.

  baseline

Secondary Outcomes (1)

• Quantitative levels of inflammatory biomarkers.

  baseline

Study Arms (2)

cases, HIV positive adolescent

This group comprises adolescents aged 13-19 years living with HIV in Eswatini, recruited from Baylor College of Medicine Children's Foundation-Eswatini Centers of Excellence and affiliated clinical sites. Participants are virally suppressed or on antiretroviral therapy (ART) and will undergo standardized neurocognitive assessments, psychosocial evaluations, and clinical data collection, including CD4+ T-cell count, plasma viral load, ART regimen history, and inflammatory biomarker profiling. No therapeutic or behavioral intervention will be administered as part of the study; all procedures are observational and non-invasive. The objective is to characterize neurocognitive performance and identify biological correlates of cognitive outcomes in adolescents with perinatally acquired HIV.

Group: HIV-Negative Adolescents

This group consists of adolescents aged 13-19 years who are HIV-negative, recruited from Raleigh Fitkin Memorial (RFM) Hospital in Eswatini. Participants will undergo the same standardized neurocognitive assessments and psychosocial evaluations as their HIV-positive counterparts. No therapeutic or behavioral intervention will be administered; all procedures are observational and non-invasive. This group serves as a control population to facilitate comparative analyses of neurocognitive performance and inflammatory biomarker profiles, thereby helping to isolate the effects of HIV infection on neurodevelopmental outcomes

Eligibility Criteria

• Age: 13 Years - 19 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

The study population will encompass all adolescents attending RFM hospitals, Baylor RFM, and Baylor Mbabane: 1. Adolescents aged 13 to 19 years who are on antiretroviral therapy (ART) and attending the Baylor clinic at RFM and Baylor Mbabane. 2. HIV-negative adolescents aged 13 to 19 years who meet the inclusion criteria and are consulting at the RFM hospital outpatient department.

You may qualify if:

• Cases
• Adolescents aged 13-19 years
• HIV-positive
• Undergoing antiretroviral therapy at Baylor Clinic
• Providing consent or assent to participate
• Controls
• Adolescents aged 13-19 years
• HIV-negative
• Providing consent or assent to participate

You may not qualify if:

• Recent (within 2 months) acute conditions: influenza, COVID-19, TB, acute gastroenteritis (as these conditions elevate CRP levels)
• Chronic conditions: diabetes, hypertension, asthma
• Neurological disorders: epilepsy, cerebrovascular accident, neurodegenerative diseases
• History of significant cranial trauma or perinatal complications
• All the aforementioned conditions will be identified through self-reported data and medical records.

Sponsors & Collaborators

• Eswatini Nazarene Health Institutions: lead
• Baylor Foundation Eswatini: collaborator

Study Sites (1)

Eswatini Nazarene Health Institution, Baylor College of Medicine Children's Foundation-Eswatini (Centers of Excellence in Mbabane and satellite clinic in Manzini in Raleigh Fitkin Memorial Hospital)

Manzini, M200, Eswatini

Location

Related Publications (6)

• Swanta N, Aryal S, Nejtek V, Shenoy S, Ghorpade A, Borgmann K. Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV. J Neurovirol. 2020 Jun;26(3):358-370. doi: 10.1007/s13365-020-00834-3. Epub 2020 Mar 19.

  PMID: 32193795 BACKGROUND

• Moschopoulos CD, Stanitsa E, Protopapas K, Kavatha D, Papageorgiou SG, Antoniadou A, Papadopoulos A. Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review. Life (Basel). 2024 Apr 15;14(4):508. doi: 10.3390/life14040508.

  PMID: 38672778 BACKGROUND

• Mouchati C, El Kamari V, Sattar A, Yu J, McComsey GA. Comprehensive assessment of neurocognitive function, inflammation markers, and adiposity in treated HIV and control. Medicine (Baltimore). 2022 Oct 21;101(42):e31125. doi: 10.1097/MD.0000000000031125.

  PMID: 36281153 BACKGROUND

• Kapetanovic S, Giganti MJ, Abzug MJ, Lindsey JC, Sirois PA, Montepiedra G, Canniff J, Agwu A, Boivin MJ, Weinberg A; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network. Plasma biomarker factors associated with neurodevelopmental outcomes in children with perinatal HIV infection and controlled viremia. AIDS. 2021 Jul 15;35(9):1375-1384. doi: 10.1097/QAD.0000000000002862.

  PMID: 33710019 BACKGROUND

• Hoare J, Myer L, Heany S, Fouche JP, Phillips N, Zar HJ, Stein DJ. Cognition, Structural Brain Changes, and Systemic Inflammation in Adolescents Living With HIV on Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2020 May 1;84(1):114-121. doi: 10.1097/QAI.0000000000002314.

  PMID: 32032303 BACKGROUND

• Anderson AM, Jang JH, Easley KA, Fuchs D, Gisslen M, Zetterberg H, Blennow K, Ellis RJ, Franklin D, Heaton RK, Grant I, Letendre SL. Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection. J Acquir Immune Defic Syndr. 2020 Dec 15;85(5):617-625. doi: 10.1097/QAI.0000000000002484.

  PMID: 32932412 BACKGROUND

Related Links

• Peer-reviewed article in Journal of NeuroVirology (2020) identifying blood-based inflammatory biomarkers-such as CCL8, TIMP-1, and IL-23-associated with neurocognitive impairment in people living with HIV, using multivariate regression analysis
• Peer-reviewed article in Medicine (Baltimore) (2022) examining associations between inflammatory biomarkers and neurocognitive function in people living with HIV, highlighting links between systemic inflammation and cognitive impairment.
• This study investigates how plasma biomarkers-such as sCD14, IL-6, and TNF-α-correlate with neurodevelopmental outcomes in children with perinatal HIV who are virally suppressed. It's a key reference for understanding the biological mechanisms underlying
• Peer-reviewed article from the \*Journal of NeuroVirology\* (2020) examining how earlier antiretroviral therapy initiation in youth with vertically transmitted HIV is associated with improved brain structure and working memory-related neural activation.
• ClinicalTrials.gov protocol entry for "The Eswatini Study on Neurocognitive Performance in Adolescents Living With HIV," detailing study identification, design, outcome measures, data sharing plans, and references for related publications and supporting

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Phathizwe M Mantshana, BSc

  Eswatini Nazarene Health Institution

  PRINCIPAL INVESTIGATOR

• Sarah H Perry, Ass professor

  Baylor College of Medicine

  STUDY DIRECTOR

• Debrah Vambe, MD

  Baylor College of Medicine

  STUDY DIRECTOR

• Mkunde S Chachage, PHD

  University of Dar es Salaam-Mbeya

  STUDY DIRECTOR

• Clement Gascua AduGyamfi, G AduGyamfi,, PHD

  Baylor College of Medicine

  STUDY DIRECTOR

• Alfred Balasa,, Associate Professor

  Texas Children's Hospital Austin Baylor College of Medicine

  STUDY DIRECTOR

• ANDREW R DINARDO, associate professor

  Baylor College of Medicine

  STUDY DIRECTOR

Central Study Contacts

Phathizwe M Mantshana, BSc

CONTACT

+26878217451; stickenmud@gmail.com

Sarah H Perry, Associate Professor

CONTACT

+268 2409 6000; banner@bcm.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 10, 2025
• Study Start: November 30, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data from this study will be made available beginning six months after the primary publication of results.
• Access Criteria: Anonymized individual participant data will be made available to qualified members of the scientific community in accordance with the Baylor Foundation Eswatini data sharing policy. Access will be granted upon formal request and subject to review and approval procedures designed to ensure ethical use, data security, and alignment with participant consent provisions.

Locations

ES (1)