Brain impairment associated with HIV level in cerebrospinal fluid

The amount of HIV in the cerebrospinal fluid (CSF), but not the blood, is associated with the development of HIV-associated brain disorders and psychiatric disease, according to a study published in the June 2002 edition of the Annals of Neurology.

Researchers at the HIV Neurobehavioural Research Center in San Diego, California, undertook a cohort study of 139 HIV-positive people between February 1990 and April 1998. Their study had two aims: to see if people with higher HIV viral loads in the CSF were more likely to progress to neuropsychological impairment, and, second, to see if higher CSF viral loads led to a decline in the skills most likely to be affected in HIV neurocognitive disorders (attention and working memory, learning and motor skills).

The study cohort consisted of 133 men and six women. On enrolment, the average CD4 count was 378 cells/mm³. Viral load in both the blood and CSF were measured at baseline and at follow-up, an average of one year later. At baseline and at follow-up the trial participants also completed tests which assessed eight major neurocognitive ability areas.

At baseline tests suggested that 94 of the trial participants had no neuropsychiatric impairment, whi;e 45 were evaluated as impaired. On follow-up, 18 of the non-impaired group were found to have developed impairment, whilst 14 of the impaired group improved to normal.

Examination of the baseline CSF viral loads indicated that those with higher CSF viral loads were at a significantly higher risk of developing impairment. By contrast, HIV viral load in the blood was not seen to be predictive of developing neuropsychiatric disorders.

People with higher baseline CSF viral load were also found to have worsened results in tests assessing learning, attention and motor function. However, baseline CD4 count, stage of HIV disease progression using CDC classification, use of antiretorvirals, changing antiretrovirals were not predictive of the development of brain impairment.

Investigators noted that not everybody with high CSF viral loads developed brain impairment, prompting them to suggest that immune responses in the central nervous system may be protective against HIV in the CSF.

The study authors conclude: “The observation that neurocognitive decline was associated with HIV RNA levels in CSF, but not plasma, suggests that CSF viral load measurement may be important in assessing the risk of future nerocoognitive decline in HIV-infected individuals…interventions targeted at lowering both plasma and CSF viral load may be clinically warranted. Our findings also support the inclusion of tests that assess learning, attention and working memory, and motor function…to evaluate neurocognitive function in HIV-infected individuals."