Mild Neurological Impairment Is Common During Early HIV Infection

People with HIV infection often have neurological signs and symptoms very soon after becoming infected -- even before they develop antibodies that show up on a test -- but these are typically mild to moderate and resolve after starting effective antiretroviral therapy (ART), according to a study published in the June 10 advance online edition of Neurology. These findings provide further evidence for starting treatment as soon as possible after HIV diagnosis.

Neurocognitive problems, including AIDS-related dementia, were commonly seen among people living with HIV before the advent of effective treatment. Combination ART has reduced the incidence of neurological problems in this population, but low-level impairment is still a concern, especially when treatment is delayed.

Joanna Hellmuth from UCSF and colleagues looked at the incidence, timing, severity, and persistence of neurological findings among participants in an acute HIV infection cohort in Thailand. Acute infection was defined as prior to antibody seroconversion. 

A total of 139 participants identified with acute HIV infection (median estimated duration of 19 days) underwent structured neurologic testing, immediately started ART, and had follow-up evaluations at 4 and 12 weeks. Some agreed to lumbar punctures to collect cerebrospinal fluid and some received MRI scans.

Just over half of the participants had at least 1 neurological finding in the 12 weeks after HIV diagnosis, including a person who developed Guillain-Barré syndrome. There were 245 total neurological findings, reflecting cognitive symptoms (33%), motor symptoms (34%), and neuropathy (11%), according to the study abstract. Almost half of these occurred prior to ART initiation. Most symptoms improved within a month after starting treatment, with only 9% (22 findings) persisting after 24 weeks on ART.

Nearly all of these neurological findings (96%) were categorized as mild. No structural abnormalities were observed on neuro-imaging. Participants with neurological findings had higher plasma viral load, on average, than people without such symptoms.

"Acute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors," the study authors concluded. "Severe neurologic manifestations are infrequent in treated acute HIV."

Below is an edited excerpt from a UCSF news release describing the study findings in more detail.

Neurologic Symptoms Common in Early HIV Infection

Much More Extensive, Though Milder Than Previously Thought

A team led by researchers from UC San Francisco and Yale has found that half of people newly infected with HIV experience neurologic issues. These neurologic findings are generally not severe and usually resolve after participants started anti-retroviral therapy.

"We were surprised that neurologic findings were so pervasive in participants diagnosed with very recent HIV infection," said study lead author, Joanna Hellmuth, MD, MHS, clinical fellow in UCSF’s Department of Neurology. "While the findings were mild, it is clear that HIV affects the nervous system within days of infection. Since the majority of these neurologic issues were resolved with treatment, our study reinforces recommendations that people at risk for HIV test often and start antiretroviral treatment immediately if they are infected."

The research will be published in the June 10, 2016, issue of Neurology, the medical journal of the American Academy of Neurology.

The team examined 139 participants in the RV254 Thai cohort who were recently infected with HIV. The time from infection to entry into the study ranged from 3 to 56 days with a median of 19 days. At this stage, participants would not test positive on the common antibody tests for HIV since they have not been infected long enough for a robust specific immune response to take place. Fifty-three percent had neurologic findings, with a third experiencing cognitive deficits, a quarter having motor issues, and nearly 20 percent experiencing neuropathy. Many experienced more than one symptom. One participant was diagnosed with Guillain-Barré Syndrome, the only severe case found in the cohort.

"In the early days of the epidemic in San Francisco, approximately 10 percent of patients with recent HIV infection presented with dramatic neurological disease. But that was likely due to patients coming in early because of the severity of symptoms they were experiencing. The Thai cohort has given us an opportunity to look at a broad range of newly infected patients, analyze their neurological functioning systematically and follow them over time. We are gaining deeper insights into the degree to which early HIV affects the nervous system," said study senior author, Serena Spudich, MD, Yale associate professor of neurology.

All participants were offered and commenced antiretroviral treatment at diagnosis. Ninety percent of the issues present at diagnosis were resolved after one month of treatment, but 9 percent of the participants had neurologic symptoms that were still not resolved six months after starting therapy. In addition, neurological symptoms were associated with higher levels of HIV found in participants’ blood.

The study participants underwent extensive neurologic assessments. Self-reported symptoms were correlated with objective neuropsychological testing. In addition, a quarter of participants opted to undergo a lumbar puncture and almost half of the patients agreed to undergo a MRI.

"This is one of the first comprehensive studies scrutinizing the involvement of the nervous system in early infection. Since we have been able to maintain the cohort for five years now, we will be able to study whether there are any persistent abnormalities that need to be addressed. Additionally, the ubiquity of symptoms in early infection found in this study reinforces the need for the brain to be considered as a compartment containing latent HIV as we design cure studies," said study co-author, Victor Valcour, MD, PhD, UCSF professor of neurology.   

7/10/16

Reference

J Hellmuth, JLK Fletcher, V Valcour, et al. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology. June 10, 2016 (online ahead of print).

Other Source

J Sheehy, UCSF. Neurologic Symptoms Common in Early HIV Infection. News release. June 10, 2016.