The Association Between Serum Mature and Precursor Brain-Derived Neurotrophic Factor and Neurocognitive Function in People With Human Immunodeficiency Virus: A Longitudinal Study.

Abstract

Background: Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-associated neurocognitive impairment persists. We investigated the association between serum levels of mature brain-derived neurotrophic factor (mBDNF), precursor brain-derived neurotrophic factor (proBDNF), and neurocognitive changes over time among adults with HIV in sub-Saharan Africa, seeking to elucidate the interplay between neurotrophic factors and neurocognitive outcomes post-ART.

Methods: Utilizing data from the ACTG 5199 study in Johannesburg and Harare, serum mBDNF and proBDNF levels were measured via enzyme-linked immunosorbent assay. Neurocognitive performance was assessed at baseline and 24, 48, and 96 weeks using neuropsychological tests. The Friedman test and linear mixed-effects models were used to assess changes in mBDNF, proBDNF, and neurocognitive performance over time, accounting for individual variability and adjusting for multiple comparisons.

Results: Among 155 participants, there were significant cognitive improvements (P < .001) and a rise in mBDNF levels from baseline to 96 weeks. The proBDNF levels initially remained stable (P = .57) but notably increased by 48 weeks (P = .04). Higher mBDNF levels were positively associated with enhanced neurocognitive performance at 48 weeks (β = .16, P = .01) and 96 weeks (β = .32, P < .001). Similarly, higher proBDNF levels were positively associated with neurocognitive performance at 96 weeks (β = .25, P < .001).

Conclusions: This study highlights the significant association between serum BDNF levels and neurocognitive improvement post-ART in adults with HIV. However, more research is needed to replicate these findings, establish causal relationships, and explore whether BDNF-enhancing activities can improve neurocognitive outcomes in people with HIV.