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  • Scientists in the U.S. have completed a 12-year study on brain function in 402 people with HIV
  • The study found that some issues—high blood pressure, diabetes, depression—affected the brain
  • They encouraged doctors to screen and treat people with HIV for these issues to preserve brain health

When initiated and taken as directed, HIV treatment (ART) reduces and suppresses levels of HIV in the blood. At such low levels, commonly called “undetectable,” HIV cannot be detected by routinely used tests. By suppressing HIV, ART helps the immune system to begin repairing itself. The benefits of ART are so tremendous that researchers expect many ART users to have a near-normal life expectancy. However, with longer life expectancy comes issues associated with a decline in the functioning of key organ-systems.

The brain and HIV

Before ART was widely available, people with HIV were vulnerable to a wide array of life-threatening infections, some of which could infect the brain and surrounding tissue. HIV itself could cause severe and ongoing inflammation that led to sustained injury to some cells in the brain. Over time, this would result in difficulty with memory, concentration and thinking clearly. In extreme cases, a loss of personality and dementia could occur.

Today, thanks to ART, HIV-related dementia is extremely rare. Some scientists have been concerned that there would be a large increase in age-related brain issues as people with HIV become older. As a consequence, there are studies underway that assess brain health and functioning in people with HIV.

A study in the U.S.

The University of California at San Diego is a centre of excellence in the field of HIV and the brain. A team of researchers who study HIV and the brain at this university has published a study about changes in neurocognitive functioning over a span of 12 years in 402 people with HIV. The researchers found that a decline in neurocognitive functioning occurred in some participants. To their surprise, the decline was found in some younger as well as older people, all of whom used ART and who had suppressed levels of HIV.

The researchers linked the decline in neurocognitive functioning to what they called “important indirect effects of multiple, potentially treatable comorbidities that are more common among people with HIV than in the general population.” The comorbidities referred to by the researchers in the present study included issues such as high blood pressure, diabetes, depression and others mentioned later in this CATIE News bulletin.

The researchers encouraged doctors and nurses to pay increased attention to a range of comorbidities that can have a negative impact on the brain health of people with HIV.

Study details

Researchers recruited participants from the following cities:

  • Baltimore, Maryland
  • Galveston, Texas
  • New York City, New York
  • San Diego, California
  • St. Louis, Missouri
  • Seattle, Washington

Recruitment occurred between 2003 and 2007. Upon study entry, participants underwent extensive medical and neuropsychological assessments. People who had major mental health issues and/or active substance use disorder were not enrolled, as these issues can affect the brain and possibly mask underlying problems caused by HIV or other factors.

Although researchers enrolled nearly 1,600 people, they focused their analysis on 402 people who had assessments done when they entered the study and again during the years 2015 to 2020.

Researchers expected that neurocognitive function would be significantly worse in older people, so they divided participants into two groups: people younger than 60 and people aged 60 and older.

The average profile of participants upon study entry was as follows:

  • age – 43 years
  • 76% men, 24% women
  • major ethno-racial groups: Black – 46%; White – 42%; Hispanic – 11% 
  • CD4+ count – 453 cells/mm3
  • lowest-ever CD4+ count – 172 cells/mm3
  • 74% of people were on ART
  • 62% of ART users had a suppressed viral load in their blood and 87% of ART users had a suppressed viral load in the fluid that surrounded the brain (this is called the cerebrospinal fluid)
  • participants were in the study for 12 years


When researchers compared results from younger and older people, they found that both groups were generally similar, though older people were more likely to have the following:

  • hepatitis C virus co-infection
  • abnormal levels of cholesterol and other fatty substances in the blood
  • injured nerves in the hands, feet and/or legs
  • high blood pressure

Over the course of the study, more participants initiated ART and achieved a suppressed viral load.

Researchers found a similar rate of neurocognitive issues in people regardless of age. As a group, the neurocognitive functioning of participants declined modestly over time. However, within the study population, researchers were able to grade the neurocognitive functioning of some people as follows:

  • stable neurocognitive functioning – 70%
  • declining neurocognitive functioning – 24%
  • improved neurocognitive functioning – 6%

Focus on decline

The factors and health issues associated with an increased risk for declining brain function (which participants had upon entering the study or developed during its course) were identified as follows:

  • high blood pressure
  • diabetes
  • chronic lung disease (the conditions in this category were asthma or chronic obstructive pulmonary disease, or COPD)
  • painful nerves in the hands, feet and/or legs (peripheral neuropathy)
  • being prefrail or having frailty
  • depression
  • anemia
  • low levels of protein in the blood
  • liver injury (elevated levels of the liver enzyme AST in the blood)
  • a history of substance use disorder

Bear in mind

The researchers planned their study with the assumption that as participants became older the following issues would combine and lead to decreased neurocognitive functioning:

  • longer exposure to HIV
  • potential effects of ART on the brain
  • aging of other organ-systems

However, they found that certain conditions that were unrelated to HIV had a profound impact on brain health. These conditions affected both younger and older people. As a result, the researchers called for physicians and nurses to pay “increased attention” to these conditions. By addressing these other conditions, brain function can be maintained and better general health preserved.


The present study is imperfect. It could have had more participants and a comparison group of people without HIV and it could have assessed participants more frequently. It also could have collected information about diet, exercise, income and access to medical care. However, some of these interventions would have added to the complexity and cost of the study.

Previous studies in people without HIV have found links between some of the issues found in the present study and declining brain health, so the present study’s findings seem reasonable.

For the future

Perhaps in the future other studies with HIV-positive people will investigate interventions (when necessary) against cardiovascular disease, diabetes, depression and so on to assess their impact on the health and functioning of the brain in the long term.

As people with HIV continue to age, ongoing funding for aging-related research is needed.

—Sean R. Hosein


Heaton RK, Ellis RJ, Tang B, et al. Twelve-year neurocognitive decline in HIV is associated with comorbidities, not age: a CHARTER study. Brain. 2023; in press.