People with undetectable HIV age cognitively at the same rate as those without HIV

Cognitive decline in virally suppressed people with HIV followed a similar trend and speed as in people without HIV as they aged, while people with HIV who failed to achieve or maintain stable viral suppression experienced a steeper age-related decline in cognition, report Dr James Kennedy and colleagues in a large long-term study published in The Journal of Infectious Diseases.

Brain volumes in both groups of people with HIV were smaller than in people without HIV across most brain regions, but the rate of age-related volume loss was largely similar between all three cohorts, with more noticeable losses in some areas among people with unsuppressed HIV. 

The most significant conclusion of the study is that achieving viral suppression seems to normalise the age-related rate of change in cognitive function and brain volume in people with HIV compared to people without HIV, whereas in people who fail to maintain undetectable viral load despite therapy, both aspects may suffer and their decline may accelerate.

The authors also suggest that the overall lower cognitive scores of people with HIV on average compared to those without HIV at baseline may be because of the initial pre-treatment effects of the infection. They found that once those people achieve an undetectable viral load their brain ageing follows the same rate as people without HIV.

The study

Between 2008 and 2024, participants were recruited from the St. Louis area in Missouri, United States. Anyone with a history of neurological disorders such as stroke, untreated depression, or loss of consciousness for more than half an hour was excluded. The exclusion also covered those with an education of less than eight years or a substance use disorder, unless it was related to tobacco, alcohol or cannabis.

A relatively large cohort – for a neurocognitive imaging study – was enrolled, including 259 participants without HIV, 264 on treatment and virally suppressed and 84 with a detectable viral load despite therapy. Social and demographic characteristics were generally comparable between the two groups of people with HIV, while relevant differences between participants with and without HIV were adjusted for in the analyses. Participants, particularly those living with HIV, were predominantly male and African American. Participants without HIV and those with detectable HIV had an average age of 36 years, around ten years younger than those with undetectable HIV. There was only a modest difference in years of education between the groups.

Viral suppression cut-off was 50 copies and it was determined either by a blood draw at the beginning of the study or participants’ medical records.

The participants had 841 study visits in total, as the majority had only one visit while some had up to five visits. At each visit they underwent a cognitive test and then neuroimaging (an MRI scan). The four-part cognitive test included category fluency, verbal learning, and two different trail-making tests.

The category fluency test consists of asking someone to name as many items belonging to a category as they can within a given time limit, in this case animals. In the verbal learning test an examiner reads twelve words and then expects you to repeat them by memory; it’s done in three trials. The last two trail-making tests ask the participants to draw continuous lines between scattered numbers on a paper as fast as they can without lifting the pen.

Together these tests assess how fast the brain can access knowledge about meanings and concepts, how well it can process verbal information, visual attention, motor speed and cognitive flexibility.

Following the cognitive test, the participants also underwent an MRI to assess brain volume changes. The researchers examined different regions of the brain primarily to look for shrinkage known as atrophy. Atrophy of given brain regions results from cell death and structural disruptions in them, and correlates with diminished functioning of abilities controlled by these brain regions. 

Rate of cognitive ageing among the groups

Everyone’s cognition worsened with age, as expected, while people without HIV performed better than both groups with HIV. However, the more important finding is that people with undetectable HIV had a rate of cognitive ageing that matched that of people without HIV. In simple terms that means, even if at baseline people with undetectable HIV may have had a worse cognitive performance than those without HIV, the decline in cognition between the two groups followed at the same rate over time.

Find out more: Cognitive impairment, dementia and HIV

Those on treatment with detectable viral load had a steeper (more accelerated) decline in their cognitive performance as they got older. In other words, age and detectable HIV seemed to synergise to quicken the decline in these participants. 

Brain volume changes among the groups

Once again, age correlated with loss of brain volume in all groups. The participants without HIV showed greater brain volumes across most brain regions than either group with HIV. The differences in brain volume between people with undetectable HIV and those with detectable HIV were negligible, except for a few regions where those who were undetectable had greater volumes than those who had a detectable viral load.

The rate of brain volume loss with age followed at a similar pace for all three groups except for the globus pallidus and putamen. In these areas, volume loss was the fastest in those with a detectable viral load. These areas together are associated with control over movement, cognition and motivation. They are part of the basal ganglia, which are known to be especially vulnerable to HIV and may act as long-term viral reservoirs in the brain.

Concluding thoughts

By separating participants according to viral suppression and following them over time, this study helps to further clarify the overall picture. Its findings add to a slowly growing body of evidence showing that people who maintain undetectable HIV experience cognitive ageing at a similar rate to people without HIV. While average cognitive performance and brain volumes may remain slightly lower, ageing itself does not appear to accelerate once viral suppression is achieved.

On the other hand, the steeper cognitive decline observed in people with detectable viral load reinforces the importance of sustained viral control for long-term brain health. These results suggest that effective treatment can prevent a synergy between the negative effects of age and HIV on cognitive function.

It is important to note that supplementary analyses revealed additional factors such as depressive symptoms, alcohol and cannabis use, and living in a disadvantaged neighbourhood were also linked to worse cognitive performance or smaller brain volumes, suggesting that non-HIV factors shape brain health even among people with well-controlled HIV. This is an important reminder than just like for everyone else, addressing lifestyle, diet, social disadvantages and mental health in people with HIV is key for healthy cognitive ageing.