Differential Serum NGF and BDNF Levels in People Living with HIV According to Antiretroviral Therapy, Historical and Current Viro-immunological Condition. A Pilot Study

Introduction: Although HIV infection can now be kept under control in almost all people living with HIV (PLWH), these individuals are prone to developing several non-AIDS complications due to chronic immune impairments, such as HIV-associated neurocognitive disorders (HAND). Unfortunately, no marker has been identified to predict these conditions, but there is growing interest in neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Methods: In this pilot study we evaluated the serum levels of these neurotrophins in 13 antiretroviral therapy (ART)-naïve and 12 ART-treated PLWH, and in two matched groups of 13 and 12 HIV-negative volunteers, respectively. Results: ART-naïve PLWH showed higher levels of NGF (p = 0.0036) and lower levels of BDNF (p < 0.0001) in their serum compared to HIV-negative individuals. In contrast, the neurotrophin levels of ART-treated PLWH were similar to those of HIV-negative people. Furthermore, serum NGF showed a negative correlation with blood CD4+ T cell count and a positive correlation with zenith HIV-RNA. Conversely, serum BDNF had a positive correlation with blood CD4+ T cell count and CD4/CD8 ratio. Discussion: The dysregulation in neurotrophin homeostasis due to HIV infection appears to be restricted to ART-naive individuals. However, NGF and BDNF levels remain influenced by both the viro-immunological status at diagnosis and the current immune status, even after effective ART. Conclusion: These findings suggest a distinct neurotrophin signature in untreated HIV infection, as well as a strong correlation between NGF and BDNF levels and current or historical immune status. This supports the need for further exploration of neurotrophins as potential biomarkers of HAND.