Controlling HIV in the Brain
Jeffrey Laurence, M.D., and Rowena Johnston, Ph.D.
amfAR grantee Dr. Steven Deeks
May 20, 2010— In following HIV patients who have been on antiretroviral therapy (ART) for many years, researchers have begun to observe that some of these patients exhibit signs of accelerated aging, including increased risk of heart disease, some cancers, liver disease, and possibly, dementia. Since most longtime HIV patients are on treatment, scientists have been unsure about whether this premature aging process results from the body’s immune response to the virus or is a side effect of treatment. amfAR grantee Dr. Steven Deeks of the University of California-San Francisco recently addressed this question by examining virus and immune activation in the central nervous system—an area that has not been well studied to date.
As part of his study, Dr. Deeks and his colleagues looked at a small but significant group of people living with HIV: elite controllers. This group is a rare subset of people with HIV—less than one percent—who maintain virus levels in their blood below the limits of detection by standard tests without ART.
Deeks and others had previously shown that the vast majority of elite controllers have evidence of immune activation in the blood, as well as the signs of premature heart disease thought by some to be caused by such activation. This raised the possibility that immune activation that occurs despite very low viral growth might also be affecting the brain. Writing in the April issue of the journal AIDS, Deeks and colleagues from UCSF and Johns Hopkins analyzed cerebrospinal fluid (CSF), which bathes the brain and spinal cord, from eight elite controllers. These individuals had a median known duration of infection of 17 years. Deeks compared the CSF from these eight elite controllers to the CSF of three other groups: HIV-negative people; untreated HIV-positive individuals with detectable virus; and HIV-positive people successfully treated with ART. He and his colleagues assessed viral loads and three markers of inflammation and immune activation— neopterin, MCP-1, and IP-10—that characterize dementia and other neurological disorders in the setting of HIV.
Mirroring what is seen in the blood in these groups, no virus was detectable by standard tests in the CSF of elite controllers and those successfully treated with ART. On the other hand, while levels of all three activation markers were similar among elite controllers, HIV-positive individuals who were successfully treated with ART, and those who were HIV negative, they were higher in the HIV-positive individuals not on ART.
This information is important because a strong immune response targeting HIV is often associated with control of the virus. But such chronic immune activation has also been linked to metabolic complications, including accelerated osteoporosis and heart disease. The findings of Deeks and associates suggest that both elite controllers and those on ART are not at high risk for developing HIV-related neurological damage. Further studies with the elites and long-term nonprogressors could offer the opportunity to intervene with therapies targeted not at controlling the virus but at dampening the deleterious aspects of the chronic immune activation that the virus elicits.
Dr. Johnston is amfAR’s vice president and director of research and Dr. Laurence is senior scientific consultant.