For the millions living with HIV who have access to treatment, the lifelong condition is manageable rather than fatal. Still, living with a chronic condition is not easy—mentally or physically. For example, numerous studies have linked HIV comorbidities to symptoms of brain dysfunction and neurodegeneration.
Now, researchers at USC’s Mark and Mary Stevens Neuroimaging and Informatics Institute have published one of the largest-ever neuroimaging studies of HIV, giving us a much better understanding of how infection changes the human brain.
Previous studies have reported cognitive difficulties in HIV-positive populations at nearly 50%, while others suggested fewer than 20% of persons were affected. In addition to being inconsistent, the sample size examined in previous literature has been small—especially compared with this USC study—and not reflective of the impact antiretroviral medication has had on HIV treatment.
Since HIV damages the immune system by infecting CD4+ T lymphocytes, doctors often rely on a patient’s CD4+ T-cell count and HIV viral load in collected blood samples to monitor infection and treatment response. In their study, Talia Nir, Neda Jahanshad and colleagues used these biomarkers in patients’ blood, along with MRI data from 1,203 HIV-positive persons in six countries to look for any changes in the volume of various structures in the brain.
The researchers found that lower CD4+ T-cell counts were associated with less brain volume in the hippocampus and thalamus, the parts of the brain's limbic system involved in regulating memory, emotion and behavior. Detectable viral load was also associated with less brain volume in the hippocampus.
While those results were consistent across all patient populations, additional data told a different story. For example, detectable viral load was associated with smaller amygdala volumes only in those patients currently receiving HIV treatment. Meanwhile, lower CD4+ T-cell counts were associated with less brain volume in the putamen, the part of the brain that aids in movement of the limbs, only in those patients not receiving antiretroviral treatment.
The researchers note that accelerated atrophy of the hippocampus, the region that showed the most consistent effects in their study, is a hallmark of neurodegenerative diseases, such as Alzheimer's disease. Additionally, it has been proven that inflammation and blood brain barrier impairment accelerate age-related neurodegeneration—and both happen to be HIV-related pathological processes, as well.
“There are many factors that contribute to brain tissue loss and subsequent cognitive impairments as we age, and a person's immune function is no exception," said Jahanshad, associate professor of neurology and a senior author of the paper, published in JAMA Network Open. "Through these large-scale efforts, we're beginning to understand the link between immune function and brain alterations in individuals living, and aging, with HIV."
Next, Jahanshad and team will analyze imaging data over time to further understand how clinical markers of HIV infection affect the brain and the rate of neurodegeneration. As part of that ongoing work, they are inviting researchers around the world to join the ENIGMA-HIV Working Group.
"With a greater collaborative effort, we hope to be able to assess how genetic, environmental, lifestyle and treatment-related factors may further impact neurological outcomes," says Nir, a postdoctoral scholar and first author of the study.
Photo: The shift of HIV-infection from a fatal to chronic condition in the era of more widely available treatment appears to be accompanied by a shift in the profile of HIV-related brain abnormalities beyond the basal ganglia (yellow), frequently implicated in earlier studies, to limbic structures (red). Credit: Talia Nir, Neda Jahanshad, and James Stanis of the Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC.