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Observational Study
. 2025 May 3;15(1):15520.
doi: 10.1038/s41598-025-99569-6.

Dual trajectories of serum brain-derived neurotrophic factor and cognitive function in people living with HIV

Henry Ukachukwu Michael  1   2   3 , Antony M Rapulana  4   5   6 , Theresa Smit  4 , Njabulo Xulu  4 , Sivapragashini Danaviah  7 , Suvira Ramlall  8 , Frasia Oosthuizen  9
Affiliations
Observational Study

Dual trajectories of serum brain-derived neurotrophic factor and cognitive function in people living with HIV

Henry Ukachukwu Michael et al. Sci Rep. .

Abstract

This study aimed to identify the interrelationships between mature BDNF (mBDNF), precursor BDNF (proBDNF) trajectories, and cognitive performance in individuals with HIV from sub-Saharan Africa over 96 weeks following antiretroviral therapy (ART) initiation. Using data from 154 participants in the ACTG 5199 study (ClinicalTrials.gov NCT00096824, 2005-06-23) in Johannesburg and Harare (2006-2009), we measured serum mBDNF and proBDNF levels via ELISA and assessed cognitive performance with neuropsychological tests. Group-based trajectory modelling indicated two mBDNF trajectories-"Stable Ascent" (83.9%) and "Peak with Gradual Decline" (16.1%)-and two proBDNF trajectories-"Gradual Increase" (85.7%) and "Gradual Decline" (14.3%). These were linked to three cognitive trajectories: "Low Baseline-Slow Improvement," "Gradual Improvement," and "Late Surge." The "Stable Ascent" mBDNF group showed a significant probability of "Gradual Improvement" (68%) in cognitive performance and a "Late Surge" (9.5%). In contrast, the "Peak with Gradual Decline" mBDNF trajectory saw no "Late Surge." A "Gradual Increase" in proBDNF corresponded to a 67.7% chance of "Gradual Improvement" in cognition. Findings suggest BDNF isoforms as potential biomarkers for cognitive interventions in HIV, emphasizing that stable or increasing BDNF levels post-ART are linked to favourable cognitive outcomes. Further research is needed to develop BDNF-based cognitive health strategies to improve outcomes for people with HIV.

Keywords: Brain-derived neurotrophic factor; Cognition; Group-based trajectory modelling; HIV/AIDS; sub-Saharan Africa.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Kwazulu-Natl, Durban South Africa (August 18, 2022/Number BREC/00003101/2021), University of the Witwatersrand, Johannesburg, South Africa (July 28, 2021/04081), and Medical Research Council of Zimbabwe, Harare, Zimbabwe (September 10, 2021/MRCZ/E/299). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors confirm that participants provided consent for publication. The data analyzed was anonymized and presented collectively.

Figures

Fig. 1
Fig. 1
Predicted trajectory groups for serum mBDNF. “Peak with gradual decline” group (16.1%) is represented in red; “Stable Ascent” group (83.9%) is represented in blue. The shaded regions around the trajectories represent the 95% confidence intervals, illustrating the uncertainty or variability in the model’s predictions over time. Narrower shading indicates greater confidence in the predicted values. Abbreviation: mBDNF, mature brain-derived neurotrophic factor.
Fig. 2
Fig. 2
Predicted trajectory groups for serum proBDNF. “Gradual Decline” group (14.2%) is represented in red; “Gradual Increase” group (85.7%) is represented in blue. The shaded regions around the trajectories represent the 95% confidence intervals, illustrating the uncertainty or variability in the model’s predictions over time. Narrower shading indicates greater confidence in the predicted values. Abbreviation: proBDNF, precursor brain derived neurotrophic factor.
Fig. 3
Fig. 3
Predicted trajectory groups for cognitive z-score. “Low Baseline-Slow Improvement” group (24.52%) is represented in red; “Gradual improvement” group (67.74%) is represented in blue; “Late Surge” group (7.74%) is represented in green. The shaded regions around the trajectories represent the 95% confidence intervals, illustrating the uncertainty or variability in the model’s predictions over time. Narrower shading indicates greater confidence in the predicted values. Clinically, the identification of a ‘Late Surge’ trajectory is of interest as it suggests that cognitive gains may manifest later in treatment for a subset of individuals, highlighting the potential for improvement even among those with initially limited progress.
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