April 2, 2008

Even Failing Treatment Reduces HIV in the Brain

Despite having similar levels of HIV in the blood, people who continue taking a failing antiretroviral (ARV) regimen have lower levels of HIV and reduced immune activation in the brain compared with people not on treatment, according to a study published in the April 15 issue of the Journal of Acquired Immune Deficiency Syndromes. This is potentially good news for people who may be at risk for HIV-related brain disorders like AIDS dementia complex (ADC).

To protect the central nervous system, our bodies have a series of membranes—called the blood-brain barrier (BBB)—that filter blood and fluids entering the brain and cerebrospinal fluid (CSF) from the rest of the body. Scientists have noted that HIV replication sometimes differs between the blood and distinct compartments like the brain or the genital tract. It is also clear that, in addition to directly infecting and killing CD4 cells, HIV causes damage to the immune system by causing it to be in a chronically activated state. Because of this, and the fact that not all HIV drugs make it through the BBB, there has been concern that HIV replication and immune activation may be worse in the brain than in the blood, potentially leaving HIV-positive people on ARV therapy for ADC and other cognitive disorders.

Elizabeth Sinclair, PhD, of the University of California San Francisco, and her colleagues examined the results of HIV viral load tests and immune cell tests in the blood and CSF of 123 people with HIV and 14 HIV-negative volunteers. The study participants were similar in terms of age and gender and none had any evidence of neurological diseases. Sinclair’s team divided the HIV-positive patients into three groups: The first group included people not taking antiretrovirals, called “offs”; the second group included people taking antiretrovirals, but with virus levels over 500 copies, called “failures”; and the third group included people taking antiretrovirals with virus levels below 500 copies, called “successes.”

Though the offs and failures had similar levels of HIV in blood, levels of HIV in the CSF were significantly lower in the failures than the offs. When Sinclair’s team looked for signs of immune activation, specifically the presence of a CD38 receptor on the surface CD8 immune cells, they found that remaining on a failing regimen reduced the amount of activation in both the blood and the brain. The offs had activation levels in both blood and CSF that were roughly double that of the HIV negatives. Immune activation was significantly lower in the failures and lower still in the successes. As would be expected, the HIV-negative group had the lowest levels of immune activation of all the groups.

Sinclair and her team conclude that while the results of their study are promising, similar research should be carried out in people with varying levels of neurological impairment to determine how much of a role immune activation and HIV levels in CSF play in brain disorders.

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