No change in cognitive function or brain structure in people taking effective HIV treatment for 2 years

People with HIV taking antiretroviral treatment who had undetectable viral load did not suffer any loss of cognitive function or brain volume during a two-year period when compared with their HIV-negative peers, but did have lower cognitive function and brain volume at the start of the study, suggesting that changes occur before effective treatment starts, according to the findings of a study published this week in the journal JAMA Neurology.

Although a mild loss of cognitive function can be detected in up to 40% of people living with HIV it is unclear if people with HIV taking effective antiretroviral therapy will suffer a progressive decline in cognitive function, or if any deterioration in cognitive function is a result of physical changes in the brain.

To answer these questions, researchers from McGill University, Montreal (Canada), and Washington University, St Louis (USA) designed a study to follow people living with HIV for two years and compare their cognitive function and brain structure with a demographically similar HIV-negative control group.

Glossary

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.

magnetic resonance imaging (MRI)

A non-invasive, non-x-ray diagnostic technique that provides computer-generated images of the body's internal tissues and organs.

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

hypothesis

A tentative explanation for an observation, phenomenon, or scientific problem. The purpose of a research study is to test whether the hypothesis is true or not.

They recruited 23 women and 25 men living with HIV, with an average age of 47 years and 13.3 years of education. Just over two-thirds were African American (69%). People were excluded from the study if they had any history of opportunistic infections affecting the brain, traumatic brain injury, psychiatric disorder or substance use disorder. The control group consisted of 16 women and 15 men with an average of 51 years and 14.5 years of education. Fifty-two per cent were African American.

All people with HIV were taking antiretroviral treatment and had fully suppressed viral load. They had been infected with HIV for a median of 13.5 years, had a current median CD4 cell count of 630 cells/mm3 and a median nadir CD4 count of 190 cells/mm3

Cognitive function was assessed using eight tests recommended for evaluation of HIV-associated neurocognitive disorders.

Changes in the brain were assessed using magnetic resonance imaging (MRI). These scans of the brain measured changes in the volume of the brain and its various components (white matter, grey matter, cerebrospinal fluid) and changes in the thickness of the cerebral cortex.

Participants were tested and scanned twice, at an average interval of 2.1 years.

After adjusting for age, sex and educational level, people living with HIV had significantly lower scores in six of the eight tests of neuropsychological function at baseline. There was no relationship between CD4 cell count, nadir CD4 cell count or duration of infection and neuropsychological scores.

During the follow-up period, HIV-positive study participants showed no deterioration in test scores.

Differences between the two groups in the volume of several regions of the brain were detected at baseline, as well as significantly lower cortical thickness. Again, no significant changes in the brain were detected during the follow-up period.

The study authors argue that the lack of relationship between CD4 cell counts, nadir CD4 cell counts or duration of infection and most brain changes suggests that any neurocognitive deficit becomes established in the early phase of HIV infection. More work is needed, they say, to confirm the hypothesis that early treatment – within a year of infection – might reduce the prevalence of HIV-associated neurocognitive disorders (HAND).

There was no relationship between exposure to antiretroviral drugs with greater penetration into the central nervous system and neuropsychological function or brain volume, although the number of different regimens taken by study participants was too small to determine if any regimen was protective or neurotoxic.

The investigators say that the study population was large enough to detect clinically meaningful changes and that their findings mirror those of other studies that used different methods to assess changes in cognitive function in people on antiretroviral treatment.

An important limitation of their study, say the investigators, is that they can’t rule out that smaller brain volume and cognitive deficits could be partly explained by cardiovascular disease, and specifically by microvascular in the brain.

References

Sanford R et al. Association of brain structure changes and cognitive function with combination antiretroviral therapy in HIV-positive individuals. JAMA Neurology, published in advance online, 13 November 2017.