Serum Mature and Precursor Brain-Derived Neurotrophic Factors and Their Association with Neurocognitive Function in ART-Naïve Adults Living with HIV in Sub-Saharan Africa.

Abstract

This study investigates the association between serum mature brain-derived neurotrophic factor (mBDNF), its precursor proBDNF, and neurocognitive function in ART-naïve adults with HIV in sub-Saharan Africa, exploring the distinct roles of these neurotrophic factors in cognitive health. This cross-sectional analysis utilized stored baseline serum samples and neuropsychological test data from participants in the AIDS Clinical Trials Group (ACTG) A5199 study in the Johannesburg and Harare sites. Serum concentrations of mBDNF and proBDNF were quantified using ELISA. Neurocognitive function was assessed via standardized tests, with results adjusted for site-specific demographics. Linear and quantile regression models examined the relationship of mBDNF and proBDNF with a composite cognitive score (NPZ-6), and structural equation modeling (SEM) explored their association with individual cognitive test outcomes. The analysis involved 157 ART-naïve adults with HIV. Increased serum mBDNF levels showed a significant positive association with cognitive performance (β = 1.30, p = 0.02), while elevated proBDNF levels were linked to poorer outcomes, particularly affecting fine motor skills and speed (β =  - 0.29 to - 0.38, p ≤ 0.01). Quantile regression analysis highlighted mBDNF's stronger positive impact at higher cognitive performance percentiles (β = 1.04 (0.01, 2.06) at the 75th percentile), while proBDNF showed significant negative association at the 75th percentile (β =  - 0.26 (- 0.47, - 0.06)). The study highlights the positive association of mature BDNF and the negative association of proBDNF with cognitive function in HIV. These findings emphasize the need for longitudinal research to understand the temporal dynamics of neurotrophic factors during ART initiation and their potential as targets for neurocognitive interventions in HIV.