Michael Henry, Rapulana Antony, Smit Theresa, Xulu Njabulo, Danaviah Sivapragashini, Ramlall Suvira, Oosthuizen Frasia
University of KwaZulu-Natal.
Africa Health Research Institute.
Res Sq. 2025 Apr 14:rs.3.rs-4307577. doi: 10.21203/rs.3.rs-4307577/v1.
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.
本研究旨在确定撒哈拉以南非洲地区感染艾滋病毒的个体在开始抗逆转录病毒治疗（ART）后的96周内，成熟脑源性神经营养因子（mBDNF）、前体脑源性神经营养因子（proBDNF）轨迹与认知表现之间的相互关系。利用来自约翰内斯堡和哈拉雷（2006 - 2009年）的ACTG 5199研究（ClinicalTrials.gov NCT00096824，2005 - 06 - 23）中154名参与者的数据，我们通过酶联免疫吸附测定法测量血清mBDNF和proBDNF水平，并通过神经心理学测试评估认知表现。基于组的轨迹建模显示出两种mBDNF轨迹——“稳定上升”（83.9%）和“先达到峰值后逐渐下降”（16.1%），以及两种proBDNF轨迹——“逐渐增加”（85.7%）和“逐渐下降”（14.3%）。这些轨迹与三种认知轨迹相关：“低基线 - 缓慢改善”、“逐渐改善”和“后期激增”。“稳定上升”的mBDNF组在认知表现上有显著的“逐渐改善”概率（68%）和“后期激增”概率（9.5%）。相比之下，“先达到峰值后逐渐下降”的mBDNF轨迹没有出现“后期激增”。proBDNF的“逐渐增加”对应着认知方面“逐渐改善”的概率为67.7%。研究结果表明，BDNF亚型可能是艾滋病毒认知干预的潜在生物标志物，强调ART后BDNF水平稳定或升高与良好的认知结果相关。需要进一步研究以制定基于BDNF的认知健康策略，改善艾滋病毒感染者的预后。
