Protein in spinal fluid can be a marker of HIV dementia

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Measuring a protein in cerebrospinal fluid could be a way of tracking the success of treatment for HIV-induced dementia, according to data from Sweden published in the October edition of Neurology.

AIDS dementia complex is caused directly by the virus’s effect on brain tissue and also by other indirect mechanisms such as HIV viral load in cerebrospinal fluid (CSF).

Three neurofilament proteins are essential for maintaining the structure of nerve cells: light, intermediate and heavy neurofilament (NFL). NFL can be measured in CSF and is known to be a sensitive marker of nerve cell damage.

Glossary

cerebrospinal fluid (CSF)

The liquid surrounding the brain and spinal cord.

dementia

Loss of the ability to process, learn, and remember information. Potential causes include alcohol or drug abuse, depression, anxiety, vascular cognitive impairment, Alzheimer’s disease and HIV-associated neurocognitive disorder (HAND). 

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

AIDS dementia complex

A disease or infection affecting the brain. HIV-encephalopathy (also called AIDS dementia complex) is the result of damage to the brain by advanced HIV disease.

The Swedish researchers studied NFL levels in 53 men and women infected with HIV. Of these 22 had an AIDS-defining illness including nine with AIDS dementia complex (ADC). All but two were naïve to potent antiretroviral therapy, and one patient had stopped taking treatment and the other was on a failing regimen.

Twenty-one patients had raised NFL levels at the start of the study and 18 of these had an AIDS defining illness, including all nine patients with ADC. Those with ADC had significantly higher levels of NFL compared to the others with raised NFL.

After around one year of treatment with anti-HIV drugs NFL levels had fallen in all the patients except for four – all of whom still had ADC symptoms. NFL levels dropped to normal in one of these patients after two years of anti-HIV therapy but the remaining three patients did not return for follow up after the first year.

In most of the patients with ADC the drop in NFL seen over the first year corresponded with improvements in symptoms of dementia.

The authors say the study supports the concept that NFL concentrations in CSF provides a useful maker of ongoing central nervous system damage in HIV infection and could be used to monitor the success of CNS treatments.

But they also stress that raised NFL levels were seen in some patients who had not yet developed any symptoms of neurological impairment. That finding mirrors data published last year from a study of healthy, active amateur boxers which showed NFL was a sensitive marker of asymptomatic brain injury.

They add that future studies should look at NFL levels in HIV-infected people with extensive experience of antiretroviral therapy and those who have tried multiple drug treatments as they could be at greater risk of chronic CNS damage.

References

Mellgren Å et al. Antiretroviral treatment reduces CSF neurofilament protein (NFL) in HIV-1 infection. Neurology: 69: 1536-1541, 2007.