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Early Initiation of Antiretroviral Therapy Can Prevent HIV-Related Brain Damage

Jaime Rosenberg
Neurological damage begins early in infection, particularly during untreated infection, and worsens with the continued absence of combination antiretroviral therapy (cART). However, initiating cART may halt further deterioration, emphasizing the importance of early cART.
Soon after infection, HIV penetrates the brain and can cause cognitive impairment. Early initiation of combination antiretroviral therapy (cART) can prevent HIV-related brain damage, according to study findings.

Past researchers have hypothesized that structural brain alterations may occur less than a year after exposure to the virus—known as the primary stage of HIV—and progressively worsen without cART. However, course of these changes that occur shortly after infection, as well as the impact of cART, is not well-characterized.

To answer these questions, researchers assessed 65 participants in the primary stages of HIV infection from December 14, 2005, through December 22, 2011. They also included 16 participants with chronic HIV and 19 HIV-negative participants for comparison. Those with chronic HIV had a history of HIV diagnosis for at least 3 years and were either cART naïve or had elected to interrupt therapy for at least 3 months before entering the study.

Participants underwent medical and neurological examinations, and cerebrospinal fluid (CSF) specimens were collected at each visit. Blood samples were analyzed for CD4+ and CD8+ T-lymphocyte counts. To determine brain volume and cortical thickness before and after cART, the researchers applied a mixed-effects model to the brain.

A total of 184 magnetic resonance imaging (MRI) scans were collected during a median follow-up duration of 5 months. Treatment was initiated at a median of 6.5 months following HIV transmission for 30 of the participants, resulting in 123 pre-cART scans and 61 post-cART scans.

By the end of the study, those treated with cART had been receiving treatment for a median of 7.9 months and saw significant improvements in all blood and CSF biomarkers, except for albumin ratio, when comparing the first and last MRI visit.

There were no significant neurological differences between those with primary stage HIV and the HIV-negative group. However, there were significant differences in most brain regions when comparing those with primary stage HIV and those with chronic HIV. Those with chronic HIV had smaller brain volumes, thinner cortices, and enlarged third ventricles.

Longer durations of untreated infection were significantly linked to brain damage. The researchers observed volume loss in the right cerebellum, bilateral thalami, left caudate and left temporal lobe, and with cortical thinning in bilateral frontal and temporal lobes and cingulate cortex.

After the initiation of cART, there was no further brain volume loss or cortical thinning. However, longer cART duration was associated with small, but significant, increases of cortical thickness in the right frontal and temporal lobes, as well as trend level thickness increases in the left frontal and temporal lobes.

“Our findings provide a unique narrative regarding the natural course of brain volume changes in early HIV infection,” wrote the authors of the study. “We reported that atrophy and cortical thinning begins early in infection, principally during untreated infection, and worsens with the continued absence of cART. However, initiating cART may halt further structural deterioration, emphasizing the importance of early cART.”

Reference

Sanford R, Ances B, Meyerhoff D, et al. Longitudinal trajectories of brain volume and cortical thickness in treated and untreated primary HIV infection [published online April 24, 2018]. Clin Infect Dis. doi: https://doi.org/10.1093/cid/ciy362.

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