CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Background: The presence and quantification of HIV in the brain is important for eradication as neuropathological studies suggest that latent brain HIV varies considerably amongst individuals. HAND, both past and stable in virally suppressed (VS) patients is associated with brain latency and may serve as a latency biomarker discovery approach. We hypothesized that putative brain latency biomarkers would differ in VS past/stable HAND vs. non-HAND. Methods: 24 HIV+men (age M=52.67±12.72; HIV infection duration: M=17.75±12.69 years) who were VS (in plasma <100cpml and CSF <100cpml) on cART underwent lumbar puncture and neuropsychological testing. Patients with past HAND fromwhich they had recovered and patients with stable HAND (past/stable HAND group) were compared to patients with no known past or current CNS involvement (non-HAND group) for putative markers of HIV brain latency: CSF HIV RNA by single copy assay (SCA), HIV tat, BCL11b, neurofilament- light chain (NFL), neopterin, CCL2, and CSF:serum albumin ratio (Q-Alb). CSF markers were classified as normal/abnormal using normal references and a combined CSF latency biomarker risk score was created by summing the number of abnormal values. HAND status was defined using Global Deficit Score (GDS≥0.5). Past HAND was determined frommedical record review. Results: Low level HIV persistence (CSF HIV RNA SCA >1-12.4 cpml) was detected in CSF in both groups (17% of past/stable HAND and 24% of non-HAND; p=73) and HIV tat was also detected in both groups (17% of past/stable HAND and 6% for non-HAND; p=.42) (SCA was <1cpml in each case). BCL11b levels were similar across the board. However, the past/stable HAND group showed higher NFL levels (p=.05) than the non-HAND group. Neopterin was abnormal in many patients (57% of past/stable HAND and 31% of non-HAND; p=.24). CCL2 and Q-Alb levels were largely normal and similar in both groups. Consequently, the combined CSF latency biomarker risk score did not differ across groups (p=.58). Conclusion: Past/stable HAND is not a useful model for identifying brain latency biomarkers using the latter markers. Past/stable HAND remains an active virological immunological and degenerative process. The concept of a “legacy effect” from past HAND is not supported.

plasma and CSF (table 1). HIV DRM discordance was present in 3/26 (12%) paired samples. Of these, one had I84T and the other had M46I in CSF only, the third one had K101E in plasma and V106M in CSF. V3 loop was sequenced from 18/45 (40%) pairs; 94% and 83%were CCR5-using strains in the CSF and plasma, respectively (p=0.8). Conclusion: Low rates of CSF viral escape were observed and co-receptor usage was similar in both compartments. PI-associated DRMs were found in the CSF but not in plasma. Studies investigating the clinical effectiveness of PIs are warranted.

427 HERPES ZOSTER IN HIV: THE ROLE OF PLEOCYTOSIS IN SECONDARY CSF ESCAPE AND DISCORDANCE Lars Hagberg 1 , Richard W. Price 2 , Magnus Gisslén 1 1 Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, 2 University of California San Francisco, San Francisco, CA, USA Background: HIV cerebrospinal fluid (CSF) escape is defined by higher HIV RNA levels in CSF than plasma in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by higher CSF than plasma HIV RNA in untreated individuals. Secondary escape or discordance implies that the disproportionate CSF HIV RNA relates to another infection in addition to HIV. Methods: A retrospective review of people living with HIV enrolled in a cohort study or receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with HIV CSF escape (N=4), ii) treated without CSF escape (N=5), iii) untreated with HIV CSF discordance (N=8), and iv) untreated without CSF discordance (N=8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed this experience for factors contributing to CSF HIV RNA concentrations. Results: HIV CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P<0.01) and non- discordant (P<0.01) counterparts.The CSF WBC counts correlated with the CSF HIV RNA levels in both the treated (P<0.01) and untreated (P<0.01) group pairs. Moreover, the CSF WBC counts correlated strongly with the CSF:plasma HIV RNA ratios of the entire group of 27 subjects (P=<0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample, and continued for one year after HZ in one individually followed longitudinally. Conclusion: HZ provides a useful ‘model’ of secondary CSF escape and discordance. Likely, the inflammatory response to HZ pathology within the neuraxis provokes or augments local HIV production by enhanced trafficking or activation of HIV-infected CD4+ T lymphocytes. Whereas treatment and other systemic factors determine the plasma HIV-1 RNA set-point, the CSF WBC count strongly influences the relation of the CSF HIV RNA level to that set-point. Thomas Gates 1 , John Ng 1 , Tan-Nia Koh 2 , Selviana Dharmadi 1 , Sarah Palmer 3 , Vincent Morcilla 3 , Tory Johnson 4 , Avindra Nath 5 , Lucette A.Cysique 6 , Bruce J. Brew 1 , for the CHIEF Group 1 St. Vincent's Hospital, Sydney, NSW, Australia, 2 University of New South Wales, Sydney, NSW, Australia, 3 The Westmead Institute for Medical Research, Westmead, NSW, Australia, 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA, 6 Neuroscience Research Australia, Randwick, NSW, Australia 428 BRAIN HIV LATENCY BIOMARKERS

Poster Abstracts

429LB HIGH LEVELS OF CELL-ASSOCIATED HIV-1 TRANSCRIPTION IN CSF DESPITE EFFECTIVE cART

Kazuo Suzuki 1 , John Zaunders 1 , Angelique Levert 1 , Chin-Shiou Huang 2 , Takaomi Ishida 3 , Thomas Gates 1 , Caroline Rae 4 , Lauriane Juge 4 , Lucette A. Cysique 4 , John Ng 1 , Bruce J. Brew 1 1 St. Vincent's Hospital, Sydney, NSW, Australia, 2 PlexBio Co. Ltd, Taipei, Taiwan, 3 Denka Co. Ltd, Chiyoda-ku, Tokyo, Japan, 4 Neuroscience Research Australia, Randwick, NSW, Australia

CROI 2020 149