Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection

• Published in: PloS one 2016-07, Vol.11 (7), p.e0158973-e0158973
• Main Authors: Ahlgren, Erika, Hagberg, Lars, Fuchs, Dietmar, Andersson, Lars-Magnus, Nilsson, Staffan, Zetterberg, Henrik, Gisslén, Magnus
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Analysis; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Biology and Life Sciences; Blood-brain barrier; Care and treatment; Cerebrospinal fluid; Cognitive ability; Correlation; Cyanocobalamin; Dementia; Drug therapy; Female; Folic acid; Folic Acid - blood; Health aspects; Health risk assessment; HIV; HIV infections; HIV Infections - blood; HIV Infections - cerebrospinal fluid; HIV Infections - drug therapy; Homocysteine; Homocysteine - blood; Homocysteine - metabolism; Human immunodeficiency virus; Humans; Immune response; Immunoassay; Infections; Infectious diseases; Injuries; Injury analysis; Male; Mass spectrometry; Medical laboratories; Medicine and Health Sciences; Metabolism; Middle Aged; Neopterin; Nervous system; Neurofilament Proteins - blood; Neurofilament Proteins - cerebrospinal fluid; Neurons - pathology; Neurosciences; Neurovetenskaper; Nutrient deficiency; Physical Sciences; Plasma; Regression analysis; Research and Analysis Methods; Ribonucleic acid; Risk factors; RNA; Scientific imaging; Studies; Vitamin B; Vitamin B 12 - blood; Vitamin B12; Vitamin deficiency
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158973

To investigate the role of homocysteine in neuronal injury in HIV infection. Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.