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Neurologic Signs and Symptoms Frequently Manifest in Acute HIV Infection
Joanna M. Hellmuth1; James L. Fletcher2; Victor Valcour1; Eugène Kroon2; Jintanat Ananworanich3; Linda Jagodzinski3; Duanghathai Suttichom2; Nittaya Phanuphak2; Serena S. Spudich4; for the SEARCH 010/RV254 Study Group
1Univ of California San Francisco, San Francisco, CA, USA;2SEARCH, Bangkok, Thailand;3Military HIV Rsr Prog, Bethesda, MD, USA;4Yale Univ Sch of Med, New Haven, CT, USA
To determine the incidence, timing, and severity of neurologic findings in pre-antibody seroconversion acute HIV infection, as well as persistence after early combination antiretroviral therapy (cART).
A prospective cohort of participants identified through laboratory screening at an HIV/STD testing center in Bangkok, Thailand with Fiebig I-V acute HIV underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks after diagnosis. Concurrent viral and inflammatory markers in the blood and cerebrospinal fluid (CSF) were obtained, as was magnetic resonance imaging (MRI).
For the 139 participants, median estimated HIV infection duration at baseline evaluation was 19 days (range: 3-56). Seventy-three participants (53%) experienced one or more neurologic finding in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barre 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 one 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. 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), but no differences in markers of immune activation in blood or CSF. Four subjects with neurologic findings referable to the central nervous system (CNS) had undetectable CSF HIV RNA at diagnosis. No structural neuroimaging abnormalities were observed.
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 acute and early HIV in the setting of immediate treatment.