Genetic analysis and clinical studies have revealed that the AIDS virus in the cerebrospinal fluid (CSF) of some people with AIDS-related dementia evolves independently of the virus in their blood, leading to two genetically distinct forms of the virus. The finding poses a new challenge for treatment of these patients, suggesting that drugs effective against HIV-1 in their blood may not do the job in the central nervous system, and vice versa.
The discovery, by a research team from the Gladstone Institute of Virology and Immunology at UC San Francisco, was presented at the Sixth Conference on Retroviruses and Opportunistic Infections in Chicago earlier this week (February 2).
"Our data show independent viral evolution in the cerebrospinal fluid and plasma in subjects with AIDS dementia complex (ADC)," says Natalia Inkina Marlowe, PhD, lead author on the study and a postdoctoral fellow in the laboratory of Robert Grant, MD, of the Gladstone Institute. "Those with AIDS dementia may need drugs with a high capacity to penetrate the blood-brain barrier in order to treat HIV that is evolving independently in the central nervous system."
At the very least, the findings suggest that clinical trials should evaluate the success of new HIV drug treatments in the blood and the central nervous system separately, according to the research team, and success or failure in one system does not necessarily imply the same result in another.
The independent population of HIV does not appear to evolve in the CSF of neurologically normal HIV patients, the researchers found.
While the CSF and brain are different "compartments" within the central nervous system, Marlowe explains, there are parallels in their relation to systemic infection and barriers to drug penetration. As a result, the new observations may have implications for treatment of brain infection, she says.