HAART Protects the Brain From AIDS-Related Degeneration

BORAS, Sweden, Oct. 8 -- Keeping HIV at bay with highly active anti-retroviral therapy (HAART) may also forestall AIDS-related neurodegeneration, investigators have found.

Levels of neurofilament light protein in cerebrospinal fluid, a marker for brain injury, were significantly reduced after one year of HAART in 17 of 21 HIV-infected patients with high baseline amounts of the marker, reported Asa Mellgren, M.D., Ph.D., of the Clinic of Infectious Diseases SAS here, and colleagues in the Oct. 9 issue of Neurology.

Anti-retroviral therapy also appeared to prevent neurodegenerative changes for at least one year in 31 of 32 patients with normal baseline levels of neurofilament light protein in CSF, the researchers found.

The investigators had previously shown that levels of neurofilament light protein were significantly increased in the cerebrospinal fluid of patients with AIDS dementia complex, and that the levels correlated with severity of neurologic symptoms. They had also showed that in some neurologically asymptomatic patients with low CD4 T-cell counts, neurofilament light protein levels were only slightly elevated.

So they conducted a retrospective cohort study to evaluate the effects of HAART on the brain-injury marker in 53 HIV-positive patients with and without AIDS dementia complex, using archived cerebrospinal fluid samples from lumbar punctures done before and after the initiation of the drug regimen.

The researchers measured neurofilament light protein levels using enzyme-linked immunosorbent assay (ELISA) with a reference value for normal of less than 250 ng/L.

They found that 21 patients had increased levels of the marker at baseline, with a median of 780 ng/L, intraquartile range 480 to 7300 ng/L. Eighteen of these patients had an AIDS-defining condition: nine had AIDS dementia complex, five had pneumocystis jiroveci pneumonia, one had candida esophagitis, two were infected with mycobacterium avium complex, and one had the wasting syndrome.

At baseline, the patients with AIDS dementia complex also had significantly

higher neurofilament light protein concentrations than the neurologically normal patients, with a median level of 8,000 ng/L (interquartile range 1690 to 9700 ng/L) compared with 518 ng/L (interquartile range 451 to 780, P

They noted that the study was limited by its retrospective design and short follow-up. In addition, since all but two patients had never previously received anti-retroviral therapy, the findings may be applicable only to treatment-nave patients.

"Multiple-drug-experienced patients and patients on salvage therapy, who may be at greater risk of chronic CNS damage, need to be assessed in future studies," they wrote. "Indeed, neurofilament light protein measurement needs to be applied to a larger prospective longitudinal study that also includes more extensive neurologic assessments, including detailed neurocognitive testing."