Brain Derived Neurotrophic Factor and Cognitive Status: The Delicate Balance Among People Living with HIV, with and without Alcohol Abuse

Introduction: The advent of combination antiretroviral therapy(cART) has lead to a significant reduction in morbidity and mortality among people living with HIV(PLWH). However, HIV-associated neurocognitive disorders (HAND) still remain a significant problem. One possible mechanism for the persistence of these disorders is through the effect of HIV on brain-derived neurotrophic factor (BDNF). BDNF is influenced by various factors including hazardous alcohol use (HAU), which is prevalent among PLWH. This study attempts to elucidate the relationships between HAU, BDNF and HAND. Methods: Cross-sectional analyses were conducted on a sample of 199 hazardous alcohol users and 198 non-HAU living with HIV. Members of each group were matched according to sociodemographic characteristics and CD4 count. Research procedures included validated questionnaires, neuropsychological assessments and a blood sample to obtain BDNF and immune measurements. Results: Hazardous alcohol users showed either significantly lower or significantly higher BDNF levels compared to the Non-hazardous (OR=1,4; 95% CI: 1-2.1, p = 0.003). Therefore, for additional analyses, subjects were categorized based on BDNF values in: Group 1 < 4000, Group 2: 4001-7,999 (reference group), and Group 3 for those >8,000 pg/mL. Groups 1 and 3 performed significantly worse than those in Group 2 in the domains of processing speed, auditory-verbal and visuospatial learning and memory. Multivariate analyses confirmed that HAU and BDNF are significant contributors of HAND. Conclusion: Our findings offer novel insights into the relationships between BDNF, and alcohol use among PLWH. Our results also lend support to expanding clinical movement to use BDNF as an intervention target for PLWH, in those with evidence of deficiencies, and highlight the importance of including HAUat the inception of clinical trials.