Neurologic issue dog those newly infected

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A team led by researchers from University of California San Francisco and Yale University 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, Dr Joanna Hellmuth, 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 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. According to the study, 53% had neurologic findings, with a third experiencing cognitive deficits, a quarter having motor issues, and nearly 20% 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% 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, analyse 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, Dr Serena Spudich, Yale associate professor of neurology.

All participants were offered and commenced antiretroviral treatment at diagnosis – 90% of the issues present at diagnosis were resolved after one month of treatment, but 9% 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 scrutinising 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, Dr Victor Valcour, UCSF professor of neurology.

Abstract
Objective: To determine the incidence, timing, and severity of neurologic findings in acute HIV infection (pre–antibody seroconversion), as well as persistence with combination antiretroviral therapy (cART).
Methods: Participants identified with acute HIV were enrolled, underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks. Concurrent brain MRIs and both viral and inflammatory markers in plasma and CSF were obtained.
Results: Median estimated HIV infection duration was 19 days (range 3–56) at study entry for the 139 participants evaluated. Seventy-three participants (53%) experienced one or more neurologic findings in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barré syndrome). A total of 245 neurologic findings were noted, reflecting cognitive symptoms (33%), motor findings (34%), and neuropathy (11%). Nearly half of the neurologic findings (n = 121, 49%) occurred at diagnosis, prior to cART initiation, and most of these (n = 110, 90%) remitted concurrent with 1 month on treatment. Only 9% of neurologic findings (n = 22) persisted at 24 weeks on cART. Nearly all neurologic findings (n = 236, 96%) were categorized as mild in severity. No structural neuroimaging abnormalities were observed. Participants with neurologic findings had a higher mean plasma log10 HIV RNA at diagnosis compared to those without neurologic findings (5.9 vs 5.4; p = 0.006).
Conclusions: Acute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in treated acute HIV.

Authors
Joanna Hellmuth, James LK Fletcher, Eugène Kroon, Jintana Intasan, Suwanna Puttamaswin, Nittaya Phanuphak, Peeriya Prueksakaew, Jintanat Ananworanich, Shelly J Krebs, Bonnie Slike, Linda L Jagodzinski, Sukalaya Lerdlum, Mantana Pothisri, Jared Narvid, Isabel Allen

University of California, San Francisco material
Neurology abstract


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