Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection.

Erika Ahlgren,Lars Hagberg,Lars-Magnus Andersson,Henrik Zetterberg,Dietmar Fuchs,Staffan Nilsson,Magnus Gisslén,Lishomwa C Ndhlovu

doi:10.1371/journal.pone.0158973

Abstract

ObjectiveTo investigate the role of homocysteine in neuronal injury in HIV infection.MethodsUsing 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.ResultsA 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).ConclusionA 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.

Highlights

Prior to the discovery of effective antiretroviral therapy (ART), HIV-infected individuals had about a 30% overall risk of developing HIV-related dementia (HAD) [1]
A significant correlation was found between plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL) concentrations in untreated individuals (r = 0.52, p < 0.0001)
The correlation of plasma homocysteine and CSF NFL was present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016)

Summary

Introduction

Prior to the discovery of effective antiretroviral therapy (ART), HIV-infected individuals had about a 30% overall risk of developing HIV-related dementia (HAD) [1]. Recent studies have noted increased levels of cerebrospinal fluid (CSF) neurofilament light protein (NFL) in HIV-infected individuals, which is interpreted as a sign of ongoing neuronal injury. Elevated levels of CSF NFL have been reported in individuals with neurological symptoms, and in some individuals with and without ART who are asymptomatic with regard to neurological symptoms [3,4]. Associations between elevated plasma homocysteine levels and cognitive impairment in HIV-negative individuals have been the topic of many studies. Data suggest an association between elevated levels of homocysteine and diseases of cognitive impairment such as Alzheimer’s [5,6]. In the case of HIV-infected individuals, data on homocysteine levels in the context of CNS injury and neurocognition are rare. This study investigates the possible association between homocysteine and neuronal injury in HIV-1-infected individuals

Methods

Results

Discussion

Conclusion