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

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.

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

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

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.