Association Between Inflammation Biomarkers and Neurocognitive Performance Among Adolescents Living With HIV in Eswatini
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Neurocognitive performance
Study Overview
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.
Detailed Description
Adolescents living with HIV (ALHIV) in sub-Saharan Africa face a complex health burden that goes beyond virological control. In Eswatini, where HIV prevalence ranks among the highest globally, the combination of chronic infection, immune dysregulation, and neurodevelopmental vulnerability poses a significant public health challenge. Although antiretroviral therapy (ART) has greatly improved survival rates, emerging evidence indicates that ongoing immune activation may lead to subtle yet clinically significant neurocognitive deficits in youth. These impairments can impact academic performance, psychosocial functioning, and long-term quality of life.
This study aims to explore the biological correlates of neurocognitive performance in ALHIV, with a particular focus on inflammatory biomarkers. It seeks to determine the extent to which systemic inflammation measured through specific immunological markers relates to cognitive functioning in adolescents and whether these associations differ between HIV-positive and HIV-negative individuals.
Utilizing a case-control design, the study will generate comparative data to enhance understanding of the neuroimmune interface in this population. Study Population and Recruitment The study will enroll 80 adolescents aged 13 to 19 years, consisting of: 50 HIV-positive participants, recruited from HIV care centers at Baylor College of Medicine Children's Foundation-Eswatini (Manzini & Mbabane), and Raleigh Fitkin Memorial Hospital. 30 HIV-negative controls, matched by age and sex, recruited from the same geographic catchment areas to ensure contextual comparability. Eligibility criteria include confirmed HIV status (positive or negative), age within the specified range, and capacity to participate in neurocognitive testing. Exclusion criteria include acute illness, neurological disorders unrelated to HIV, or inability to provide informed consent/assent.
Neurocognitive Assessment Protocol Cognitive functioning will be assessed using the Symbol Digit Modalities Test (SDMT), a standardized neuropsychological instrument sensitive to changes in processing speed and attention. The SDMT is particularly suitable for use in low-resource settings due to its minimal language dependence and brief administration time. It evaluates: Visual scanning Psychomotor speed Sustained attention Working memory Testing will be conducted in a quiet, controlled environment by trained research personnel fluent in local languages and familiar with adolescent developmental norms.
Biomarker Collection and Analysis Venous blood samples will be collected from all participants under sterile conditions. Samples will be processed and stored according to biosafety protocols and analyzed using enzyme-linked immunosorbent assay (ELISA) techniques. The following biomarkers will be quantified: C-reactive protein (CRP): A general marker of systemic inflammation. Soluble CD14 (sCD14): Reflects monocyte activation and microbial translocation. Lipopolysaccharide (LPS): Indicates gut barrier dysfunction and endotoxemia. Soluble CD163 (sCD163): Associated with macrophage activation and neurodegeneration. Monocyte chemoattractant protein-1 (MCP-1): A chemokine involved in leukocyte recruitment and neuroinflammatory signaling. These biomarkers were selected based on their relevance to HIV-associated immune activation and their potential role in neurocognitive outcomes.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 13 Years to 19 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Adolescents aged 13-19 years
- •HIV-positive
- •Undergoing antiretroviral therapy at Baylor Clinic
- •Providing consent or assent to participate
- •Adolescents aged 13-19 years
- •HIV-negative
- •Providing consent or assent to participate
Exclusion Criteria
- •Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Neurocognitive performance
Time Frame: baseline
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.
Secondary Outcomes
- Quantitative levels of inflammatory biomarkers.(baseline)