First study of people with HIV on long-term ART shows cognitive decline

People with HIV on long-term antiretroviral therapy show signs of brain damage and cognitive impairment on a battery of imaging, laboratory, and functional tests, and they report a greater degree of difficulty with the routine tasks of everyday life, according to a new study. 

The study, published in April in the journal Neurology, is the first to gauge cognitive changes in HIV patients on antiretroviral therapy (ART) for at least 15 years. Ulisses Santamaria, with the Clinical Research Program at the Frederick National Laboratory for Cancer Research collaborated on the research led by Bryan Smith of the National Institute of Neurological Disorders and Stroke.  

When compared with an HIV-negative control group, people with HIV had poorer attention spans and working memory, and slower motor control. They were more depressed, had reduced brain volume, and showed signs of neuronal injury and inflammation. They also told of difficulties with daily activities. 

“This study is the first to characterize these outcomes with a focus on prospectively defined, long-duration HIV and long-duration ART use with a well-matched group of controls,” the scientists reported. 

The study collected test data from 155 people with HIV on ART for at least 15 years and 100 HIV-negative individuals with demographics matched to the HIV population itself. The study evaluations included medical histories; functional assessments of attention, memory, and motor function; MRI scans; and cerebrospinal fluid analyses. 

People with HIV took longer than members of the control group to complete tasks involving attention and working memory, were nearly four times as likely to say they have experienced cognitive impairments, and more than seven times as likely to have some degree of depression. 

People with HIV had smaller brain volume (specifically in subcortical gray matter) compared to controls. Forty-nine people with HIV and 23 members of the control group underwent analysis of cerebrospinal fluid. This showed “significant effects” of HIV infection on neurofilament light chain, a biomarker for neuronal damage. 

The researchers suggested that these findings might help inform future approaches to treatment for a population that continues to grow and be sustained over time by infection-controlling ART. Until HIV can be completely eradicated from affected individuals, additional therapies might be considered to support their neurologic health, the report said.  

“Depression has been associated with cognitive impairment and represents a potentially modifiable factor that clinicians should be aware of in this population,” the scientists wrote, as one example of a way to support the health of people with HIV on long-term ART.