The effect of vitamin B supplementation on neuronal injury in people living with HIV: a randomized controlled trial

Abstract

Effective antiretroviral therapy has radically changed the course of the HIV pandemic. However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomised controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12 μmol/L. They were randomised (1:1) to either active treatment (with cyanocobalamin 0.5 mg, folic acid 0.8 mg, and pyridoxine 3.0 mg) q.d. or to a control arm with a cross-over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, p < 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7 μmol/L (95% CI 14.7–16.7) to 10.3 μmol/L (95% CI 9.3–11.3) in the active treatment arm between baseline and month 12. No significant change was detected in the control arm during the same time period (geometric mean 15.2 [95% CI 14.3–16.2] vs geometric mean 16.5 μmol/L [95% CI 14.7–18.6]). A significant difference in change in plasma homocysteine levels was seen between arms at 12 months (-40% [95% CI -48 – -30%], p < 0.001). However, no difference between arms was seen in either plasma neurofilament light protein levels (-6.5% [ -20–9%], p = 0.39), or cognitive measures (-0.08 [-0.33–0.17], p = 0.53). Our results do not support a vitamin B-dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter.

Elevated homocysteine levels may moderate and mediate the association between HIV and cognitive impairment among middle-aged and older adults in an underserved population in Baltimore, Maryland

“…18,19 Low neurocognitive performance has been reported to be correlated with homocysteine levels among 57 adults with HIV. 20 A recent clinical trial examining the impact of vitamin B supplementation on neuronal injury in adults with HIV and homocysteine levels ≥12 μmol/L found a significant correlation between homocysteine levels at screening and neurofilament light protein, 21 a biomarker in neurological disorders. 21,22 However, the extent and mechanisms by which elevated homocysteine levels affect the relationship between HIV and NCI have seldom been reported, particularly in underserved populations.…”