Early Initiation of ART Could Minimize Cognitive Decline in Patients With HIV

HIV can shrink brain volumes and decrease cognitive performance in infected patients, but early initiation of combination antiretroviral therapy (ART) and steady maintenance of full viral suppression can minimize this type of brain injury, according to a new study.

Ryan Sanford MEng

Ryan Sanford MEng

“The most striking aspect of the findings is that brain volumes and cognitive performance were significantly reduced in the HIV positive group compared to well-matched controls, but the changes over 2 years were similar between groups,” said corresponding author Ryan Sanford, MEng, Department of Neurology and Neurosurgery at Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.

“This implies that differences we see in the HIV+ group may reflect changes that occur earlier in the infection time course, possibly during the time of untreated infection, suggesting that earlier treatment initiation could have significant neurocognitive benefits,” he added.

In the longitudinal case-control study, a total of 48 HIV-positive individuals who were aviremic and treated with cART, and 31 demographically similar HIV-negative controls underwent neuroimaging and neuropsychological assessment roughly 2 years apart. Data were collected from October 2011 to March 2016.

The 2 groups were demographically similar. In the HIV positive group, there were 23 women and 25 men with a mean age of about 48 years. In the HIV negative group, there were 16 women and 15 men with an average age of about 51 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.

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.

The findings indicate that cognitive and structural brain changes may occur early after serconversion, Sanford said. With that in mind, “early initiation of anti-retroviral therapy and maintaining good viral suppression with effective treatment may prevent additional accelerated brain loss. However, it is important to note that the cohort we assessed were subjects with minimal co-morbid conditions (i.e. major psychiatric disorders, active substance abuse or other neurological disorders), limiting the generalizability to individuals with similar characteristics,” Sanford told MD Magazine.

Other studies support this concept. In a presentation at ID Week in San Diego, CA, Shibani Mukerji, MD, PhD, of the Department of Neurology at Massachusetts General Hospital cited evidence showing that HIV invades the central nervous system very early in infection.

“Within days of plasma viremia, HIV RNA can be detected in the cerebrospinal fluid, and this early penetration is hypothesized to set the stage for future neurocognitive impairment,” Mukerji said. “What this really suggests is that within weeks of estimated infection, HIV may already be altering the underlying neural anatomy of our brains and altering our neural networks.”

Neurocognitive disorders also reduce the likelihood that patients with HIV will have high rates of adherence to ART, which increases viral load and the likelihood of spreading the infection.

“We’re getting new data suggesting that maybe earlier treatment for ART may improve some cognitive markers, but I think that needs to be tested out a little bit more,” she added.

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