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Abstract Details

Conserved CSF HIV Antibody Response in Central Nervous System Escape
Infectious Disease
S28 - Infectious Disease: Chronic Meningitis and the Immunosuppressed (2:24 PM-2:36 PM)
008

The CNS is exposed to HIV during primary infection and likely continuously during untreated chronic infection. ART that suppresses plasma HIV RNA also usually suppresses CSF HIV RNA. A rare exception is development of neurosymptomatic (NS) CSF escape in which CNS HIV infection develops despite plasma viral suppression. While drug resistance and incomplete drug penetration predispose to this, the origins of NS escape are not fully understood. 

To assess whether neurosymptomatic (NS) escape might be triggered by an unidentified CNS pathogen and/or whether the CSF anti-HIV antibody repertoire might distinguish NS escape.

CSF was collected from 25 HIV-infected participants, some longitudinally, with diverse neurologic phenotypes and treatment status. CSF samples were incubated with a VirScan T7 bacteriophage library expressing 481,966 peptides tiled across all known vertebrate and arbovirus genomes. Antibody-bound phage were immunoprecipitated and deep sequenced to quantify enriched viral peptides. Separately, unbiased metagenomic next-generation sequencing (mNGS) of total CSF RNA was performed. 

mNGS was 100% concordant with HIV RNA PCR for samples with ≥530 viral copies (n=15) and 0% concordant from samples with ≤113 viral copies (n=8). In addition, mNGS detected the two known infections in the secondary escape patients. Additionally, the CSF anti-HIV antibody repertoire primarily enriched two distinct epitopes within the HIV envelope protein, regardless of neurologic or treatment status. These epitopes mapped to the V3 loop near the binding site for CCR5 and to the C-terminal heptad repeat domain.

CSF mNGS did not identify additional infections in HIV NS escape. Preliminary VirScan data suggest that immunodominant epitopes in the CNS are highly conserved across patients, regardless of their neurologic status. Compared to anti-HIV epitopes previously described in sera, we identified CSF antibodies specific for the R306S mutation in the gp120 V3 region which has been associated with brain-derived env sequences and increased macrophage tropism.

Authors/Disclosures
Isobel A. Hawes (UCSF)
PRESENTER
Ms. Hawes has nothing to disclose.
Ryan D. Schubert, MD No disclosure on file
No disclosure on file
No disclosure on file
Joanna Hellmuth, MD Dr. Hellmuth has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for McAngus Goudelock & Courie law firm.
No disclosure on file
Richard W. Price, MD, FAAN (San Francisco General Hospital) No disclosure on file
Michael R. Wilson, MD, FAAN (University of California San Francisco) Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cambridge Medical Experts. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. The institution of Dr. Wilson has received research support from Chan Zuckerberg Initiative. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.