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Cognitive changes may occur early in patients on cART

Adults with human immunodeficiency virus (HIV) and good viral suppression on combination antiretroviral therapy had poorer cognition and reduced brain thickness and volume on magnetic resonance imaging than adults without HIV, but changes over time in cognitive performance and brain structure were similar between the two groups over two years, concludes a new study by Dr Ryan Sanford, of McGill University, Montreal, Canada, and co-authors.

The study involved 48 adults with HIV treated with cART with good viral suppression; 31 adults for comparison who did not have HIV; both groups were about half women, had average ages of nearly 48 (HIV-positive adults) and 51 (HIV-negative adults), and an average of 13 to 14 years of education. The study measured brain changes (cortical thickness and sub-cortical volumes) on magnetic resonance imaging (MRI) and cognitive performance using neuro-psychological assessments during a two-year period.

Treatment with combination antiretroviral therapy (cART) has helped make HIV a chronic condition but many patients experience neuro-cognitive deficits associated with HIV that affect their quality of life. It is important to know if effective cART therapy prevents brain atrophy and cognitive decline that has been observed in untreated HIV patients or in those treated but with poor viral suppression.

This is an observational study. In observational studies, researchers observe exposures and outcomes for patients as they occur naturally in clinical care or real life. Because researchers are not intervening for purposes of the study they cannot control natural differences that could explain study findings so they cannot prove a cause-and-effect relationship.

Results showed that adults with HIV had poorer cognitive performance and smaller cortical thickness and sub-cortical volumes in their brains compared with adults without HIV, but there were no significant losses in brain volume or cognitive decline over a two-year period.

Study limitations included: data on vascular risk factors were not collected so vascular injury cannot be excluded as contributing factor to smaller brain volumes and cognitive deficits; adults with HIV who were included had few comorbidities; using other tests to measure cognition could have yielded additional results.

Overall, the study concluded that changes in brain structure and cognition in HIV patients may be due to brain injury from HIV that happens earlier when the infection is untreated, and effective cART therapy with viral suppression appears to halt progression of the change.

Abstract
Importance: Despite the introduction of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders continue to be a problem for treated HIV-positive individuals. The cause of this impairment remains unclear.
Objective: To determine if detectable brain changes occur during a 2-year period in HIV-positive individuals who were aviremic and treated with cART.
Design, Setting, and Participants: In this longitudinal case-control study, participants underwent neuroimaging and neuropsychological assessment approximately 2 years apart. Data were collected from October 26, 2011, to March 1, 2016. Data from 92 HIV-positive individuals were acquired at Washington University in St Louis from ongoing studies conducted in the infectious disease clinic and AIDS Clinical Trial Unit. A total of 55 HIV-negative control participants were recruited from the St Louis community and a research participant registry. A total of 48 HIV-positive individuals who were aviremic and treated with cART and 31 demographically similar HIV-negative controls met the study requirements and were included in the analyses.
Main Outcomes and Measures: Brain volumes were extracted with tensor-based and voxel-based morphometry and cortical modeling. Raw scores from neuropsychological tests quantified cognitive performance. Multivariable mixed-effects models assessed the effect of HIV serostatus on brain volumes and cognitive performance, and determined if HIV serostatus affected how these measures changed over time. With HIV-positive participants, linear regression models tested whether brain volumes and cognitive performance were associated with measures of infection severity and duration of infection.
Results: The 2 groups were demographically similar (HIV-positive group: 23 women and 25 men; mean [SD] age, 47.7 [13.2] years; mean [SD] educational level, 13.3 [3.4] years; and HIV-negative group, 16 women and 15 men; mean [SD] age, 51.2 [12.9] years; mean [SD] educational level, 14.5 [2.1] years). The HIV-positive participants had poorer neuropsychological test scores compared with controls on the Trail Making Test Part A (5.9 seconds; 95% CI, 1.5-10.3; P = .01), Trail Making Test Part B (27.3 seconds; 95% CI, 15.0-39.6; P < .001), Digit Symbol Substitution Task (–12.5 marks; 95% CI, –18.9 to –6.0; P < .001), Letter-Number Sequencing (–2.5 marks; 95% CI, –3.7 to –1.3; P < .001), Letter Fluency (–6.6 words; 95% CI, –11.5 to –1.6; P = .01), and Hopkins Verbal Learning Test–Revised immediate recall (–2.4 words; 95% CI, –4.4 to –0.4; P = .05), after adjusting for age, sex, and educational level. Only changes in Trail Making Test Part A significantly differed between the groups. Cortical thickness and subcortical volumes were smaller in HIV-positive individuals compared with controls. However, changes in brain volume over time were similar between the groups.
Conclusions and Relevance: These findings are consistent with the idea that cognitive and structural brain changes may occur early after seroconversion, and argue that maintaining aviremia with cART can prevent or minimize progressive brain injury.

Authors
Ryan Sanford; Lesley K Fellows; Beau M Ances; D Louis Collins

[link url="https://media.jamanetwork.com/news-item/brain-structure-cognitive-function-treated-hiv-positive-individuals/"]JAMA material[/link]
[link url="https://jamanetwork.com/journals/jamaneurology/article-abstract/2661300"]JAMA Neurology abstract[/link]

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