A new study led in part by researchers at the University of North Carolina School of Medicine has found that HIV-infected cells persist in the cerebrospinal fluid of HIV patients, even after they had been receiving antiretroviral treatment for nine years or more, and the presence of these HIV-infected cells is associated with poorer neurocognitive performance.
The late Kevin R. Robertson, PhD, professor of neurology and director of neuropsychology, was co-lead author of the study, published July 15 in the Journal of Clinical Investigation. Joseph J. Eron, MD, chief of the division of infectious diseases, is a co-author.
“The relationship between HIV persistence in the cerebrospinal fluid and neurocognitive performance is critically important and deserves further study,” Eron said.
Serena Spudich, MD, of Yale University is also co-lead author of the study, and John W. Mellors, MD, of the University of Pittsburgh is senior author.
“In developing new methods to eradicate HIV, we need to look at the central nervous system more closely,” said Spudich, the Dr. Harry M. Zimmerman and Dr. Nicholas and Viola Spinelli Professor Neurology at Yale.
The persistence of HIV in sanctuary sites in the human body, despite treatment with antiretroviral therapy, is a potential barrier to HIV remission and cure. Cerebrospinal fluid, which is a part of the central nervous system and in contact with the brain and spinal cord, is one such protected compartment. This is important to understand, because neurological function is not always normal in people with well-treated HIV. Prior to this study, it was not known whether poorer thinking and cognitive function may be associated with HIV persistence in the nervous system.
The National Institutes of Health (NIH) AIDS Clinical Trial Group (ACTG) conducted the ACTG HIV Reservoirs Cohort Study (A5321), which included 69 participants with well-treated HIV. All of them underwent collection of cerebrospinal fluid and blood as well as neurocognitive assessment, which included tests of memory, learning, motor function and more. Most of these participants were male (97 percent) and had been on HIV treatment for a long time (median almost 9 years) and had a good response to their medications.
The study team examined genetic material of HIV in cells from the cerebrospinal fluid, and from fluid without cells. These tests found viral RNA (copies of the genetic material produced by the machinery in the cell) infrequently in the fluid without cells (4% of samples) but more commonly inside the cerebrospinal fluid cells (9% of cells). However, 48% of samples had viral DNA inside the cellular portion of the cerebrospinal fluid. These bits of viral DNA are copies of genetic material embedded in the cells and can sometimes make more viruses.
“This high proportion of cells within the spinal fluid with evidence of HIV was a surprise, since it suggests that more people than expected had genetic material that could encode HIV circulating in cerebrospinal fluid in the nervous system compartment,” Eron said. “Importantly, detection of the viral DNA in the cells in the cerebrospinal fluid was significantly associated with poorer performance on tests of cognition, even after taking into account the participants’ age and the severity of immune suppression they had experienced in the past.”
The study concluded that HIV-infected cells persist in the fluid that surrounds the brain and spinal cord in almost half of individuals on long-term, apparently successful treatment for HIV. The association between the presence of HIV genetic material in the cells of the cerebrospinal fluid with poorer performance on cognitive tests suggests that there may be a link between persistence of HIV in the brain compartment and neurological complications experienced by some patients.