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.