People with HIV are at an increased risk for brain inflammation and damage, similar to problems typically seen in older members of the general population, according to a series of studies presented Wednesday, February 11, at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal. The latest research also indicates this damage may not be completely halted or reversed with the use of HIV treatment.

A great deal of attention has been paid recently to the effect of HIV on the aging process, with a number of studies reported in the past year showing that people with HIV are more likely to have heart, kidney, bone and other problems at a younger age than HIV-negative people. One possible reason for this: HIV exacerbates cellular damage and further inhibits the body to heal itself, both considered to be natural consequences of growing older.

Research presented at CROI also suggests that HIV can speed up the aging process in the brain, sobering findings in light of other data presented in Montreal indicating high rates of peripheral nerve damage in people infected with the virus.

The Lower the CD4s, the Higher the Risk

Igor Grant, MD, from the University of California in San Diego (UCSD), shared data involving 1,555 HIV-positive patients enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study. Eight-five percent of those enrolled were on antiretroviral (ARV) therapy at the beginning of the study, and 63 percent had a history of an AIDS diagnosis. The average lowest-ever CD4 count was 174. At the first study visit, 47 percent of the patients had normal cognitive functioning, 21 percent had mild impairment, 30 percent had moderate impairment, and only 2 percent had severe impairment.

Although Grant and his colleagues found, to their surprise, that the rate of cognitive problems in the CHARTER study participants had not improved significantly since the early days of the epidemic, they did find a strong connection between lowest-ever CD4 count, called the nadir, and the likelihood of cognitive impairment. People who’d never had a CD4 count below 200 and who kept their virus levels under 50 copies were much less likely to have cognitive impairment.

One disturbing finding by Grant’s team was that when they used an ultra sensitive viral load test on cerebrospinal fluid—a measure of what’s going on the brain—they found that 41 percent of people with an undetectable viral load in the blood did have very low levels of virus in the brain.

Grant surmised that waiting to start ARV therapy until CD4 cells drop below 200 could initiate a cycle of brain injury that subsequent treatment with HIV drugs cannot fully shut down.

Damage Without Symptoms

Signs of brain inflammation—a potential brain damage prerequisite—is very common in people living with HIV, according to findings presented by Bradford Navia, MD, PhD, from Sackler School of Biomedical Sciences at Tufts University in Boston. His group shared data on 263 HIV-negative and HIV-positive patients, all of whom were assessed using brain imaging technology that included magnetic resonance spectroscopy (MRS). The patients were on the older end of the spectrum, with the average age being 47, and more than one third being older than 50.

Most of the HIV-positive patients have been infected for at least 12 years, and the average nadir CD4 count was less than 50. One hundred twenty-two had no neurological symptoms at baseline, 64 had very mild symptoms of dementia, and 49 had moderate to severe dementia.

Navia and his colleagues found that all of the HIV-positive patients, including those with no symptoms, had increased levels of brain inflammation proteins. However, further analysis revealed that only elevations of proteins in the basal ganglia—which connects several parts of the brain and is involved in motor control, thinking, learning and emotions—were associated with having nuerological impairment. When combined with older age, basal ganglia inflammation was a significant predictor of reduced brain functioning.

Navia’s results were similar to those presented by Beau Ances, MD, PhD, from the Washington University School of Medicine in St. Louis. Ances showed the results of functional brain images, in which the researchers took an image of a person’s brain while at rest and again while attempting to perform a mental task. Ances and his team looked at the level of blood flow to the brain in 35 HIV-negative and HIV-positive people—half of those living with HIV were receiving ARV therapy—to determine what influence HIV and aging may have on brain function.

Ances and his colleagues found that at baseline, people with HIV at rest had a reduction in blood flow that was similar to an HIV-negative person who was 10 years older. When they conducted imaging on people as they sought to perform tasks, they found that the degree of reduced blood flow to the brain was even more pronounced, with HIV-positive patients having the blood flow of a person 15 to 20 years older.

Reduced blood flow to the brain can lead, in the short term, to reduced brain function, and over time, to brain injury. Though Ances did not look specifically for the underlying causes of the reduced blood flow, he speculated that it could be from increased inflammation in the blood vessels and changes to blood platelet functioning, which could lead to reduced blood flow throughout the body. He commented that although there was no difference in blood flow based on the type of ARV treatment a person took, being on treatment with an undetectable viral load did result in higher blood flow to the brain.