The decrease in brain function seen in a 12-year study of people with HIV was worse than would be expected for typical ageing. This decrease was linked to diabetes, high blood pressure, chronic lung disease, depression, nerve pain and cannabis use. HIV itself did not appear to worsen brain function, nor was there a significant difference in brain function decline between different age groups.
Since the introduction of antiretroviral treatment (ART) and improved life expectancy of people living with HIV, there have been concerns around the effects of ageing. In 2010, the CHARTER study concluded that previous immunosuppression was linked to worsening brain function. Therefore, it was expected that HIV disease characteristics would influence brain function over time. In this study Dr Robert Heaton and his colleagues followed up the CHARTER participants to track changes in brain function and the impact of age and medical conditions. The study, published in the journal Brain, showed that the participants had faster decline in their brain function compared to what would normally be expected. The researchers were surprised to find that these changes seemed to be unrelated to increasing age or HIV, but instead were predicted by other medical conditions and drug use. This highlights the importance of diagnosing and managing these other medical conditions in people living with HIV.
Overall, 1597 people living with HIV were interviewed for this prospective study at six different US medical centres, between 2003-2007. Those with active opportunistic infections, major substance use problems or severe mental health issues were excluded, as this would have prevented them from undergoing a full day assessment. An average of 12.4 years later, 402 people were interviewed again to compare their brain function, medical conditions and medications after this time. Seven different types of tasks controlled by the brain such as memory and language, were tested in a 2-3 hour long interview to measure brain function. Bloods tests, medical examination, urine samples and spinal fluid samples were also completed at both appointments. Frailty assessments were only conducted at the second visit.
The participants aged over 60 (35%) at the follow up assessment were compared to those under 60 (65%). Overall, 76% were male, 46% were of African ancestry, 42% were described as non-Hispanic White ethnicity and 11% were Hispanic, similar to the group that were not re-interviewed. Brain function tests were done at each assessment, in order to see if there was any deterioration. We would expect there to be some decrease in brain function with age, so the brain function test results were adjusted according to what would be expected at a specific age, as well as other demographics like education. The difference in these scores between the baseline and follow up were compared, to give an indication of those participants whose brain function had worsened over time.
At the follow up assessment, participants were more likely to be using ART, more likely to be virally suppressed and were less likely to be currently depressed. As would be expected after 12 years, levels of other medical conditions like high cholesterol, high blood pressure and diabetes had increased in both age groups. There were also higher levels of previous cannabis use and hepatitis C. The number of AIDS diagnoses had also increased, although this diagnosis could have been at any point over 12 years, with generally much better control of HIV at the time of the second assessment.
For both age groups and at both time periods, there were high levels of reduced brain function compared to what would be expected for their gender, race, education and age. It had been thought prior to this study that the older age group would show faster decline, as it was thought that the risk of age-related problems in people with HIV multiplied with increased age – known as ‘accelerated ageing’. Surprisingly, there was no significant difference in the decline of brain function scores between the over and under 60 age groups.
When comparing individual participants’ brain function over time, 24% had a decline in their brain function, 70% remained stable and 6% improved. Significant risk factors that were identified at baseline assessment to predict worsening brain function at follow up included high blood pressure, chronic lung disease, high ALT liver enzyme, low blood protein levels, depression or ever having had issues with substance misuse. Surprisingly, HIV variables such as CD4 count, viral load, ART or AIDS were not good predictors for worsening brain function. This may be because most of the participants were virally suppressed on ART at the final assessment, as opposed to the earlier assessment when there was more uncontrolled HIV. Participants in the older age group with a detectable level of HIV had a greater decline in brain function at follow up compared to younger people with detectable levels of HIV.
As Dr Heaton and his colleagues noted: “These results are not consistent with premature or accelerated neurocognitive aging due to HIV itself but suggest important indirect effects of multiple, potentially treatable comorbidities that are more common among people with HIV than in the general population.”
It is worth noting that without a direct comparison to a group of people not living with HIV, these findings cannot be conclusively said to be only true of people living with HIV. The findings are still important, as the researchers note: “Apart from lifetime (not current) cannabis use disorder, the other comorbidities are potentially treatable and may deserve increased attention in the clinical management of people with HIV.”
Heaton RK et al. Twelve-year neurocognitive decline in HIV is associated with comorbidities, not age: a CHARTER study. Brain, online ahead of print, 7 December 2022.