CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

443 CEREBRAL FUNCTION PARAMETERS IN PEOPLE LIVING WITH HIV SWITCHING INTEGRASE INHIBITOR Borja Mora-Peris 1 , Laura Else 2 , Jaime Vera-Rojas 3 , Caire Petersen 1 , Maryam Khan 1 , Sujan Dilly Penchala 2 , Sofia Toniolo 3 , Mara Cercignani 3 , Michael R. Keegan 4 , Saye Khoo 2 , Alan Winston 1 1 Imperial College London, London, UK, 2 University of Liverpool, Liverpool, UK, 3 Brighton and Sussex Medical School, Brighton, UK, 4 ViiV Healthcare, London, UK Background: Different antiretroviral therapy (ART) agents and combinations may have differing effects on cerebral function. We assessed detailed changes in cerebral function parameters in people-living-with HIV (PLWH) on ART switching integrase inhibitor. Methods: Neurologically asymptomatic PLWH on tenofovir-DF/emtricitabine plus raltegravir 400mg twice daily with plasma HIV RNA <20 copies/mL for at least 3 months were randomly allocated on a 1:2 basis to remain on raltegravir (Arm1) or to switch to dolutegravir 50 mg once daily (Arm2) for 120 days. Changes in several cerebral function parameters were assessed which included cognitive function (reported as a z-score composite of 7 domains), patient-reported outcome measures (PROMs; PHQ-9 and Beck’s depression questionnaires), cerebrospinal fluid (CSF) parameters (CSF HIV RNA, tryptophan and phenylalanine metabolites, neopterin, ART exposure and an in-vitro CSF antiretroviral infectivity assay using astrocyte derived cell cultures) and cerebral magnetic resonance (MR) imaging (proton spectroscopy (H1-MRS) in three anatomical locations). CSF infectivity models are expressed as half-maximal inhibitory concentration scores (-log2IMIC50) and ART concentrations were measured by HPLC–tandemmass spectrometry with geometric means (GMs) and 95% CIs calculated. Results: Of 20 subjects completing study procedures, 19 were male, 14 were of white ethnicity, median age (IQR) was 43 (11.5) years and mean (SD) baseline CD4+count was 717 (298) cells/µL. No treatment related adverse events were observed and plasma HIV RNA remained <20 copies/mL in all. Over 120 days, no statistically significant differences in changes in overall cognitive performance, PROMs, CSF tryptophan metabolite ratios, CSF antiretroviral activity scores or cerebral metabolite ratios were observed (table 1). A small difference was observed in CSF neopterin concentration between treatment arms (table 1). CSF HIV RNA was <5 copies/mL at day 120 in all subjects. GM CSF dolutegravir concentration assessed pre-dose was 7.6 ng/mL (95% CI: 5.2-11.1). Conclusion: In this comprehensive assessment of cerebral function parameters in virologically suppressed PLWH switching integrase inhibitor, we observed no significant changes in clinical, CSF biomarker or cerebral imaging parameters.

1 University of Hawaii at Manoa, Honolulu, HI, USA, 2 SEARCH, Bangkok, Thailand, 3 University of Missouri St Louis, St Louis, MO, USA, 4 Henry M Jackson Foundation, Bethesda, MD, USA, 5 Yale University, New Haven, CT, USA Background: CX3CR1 on immune cells drives tissue homing. In chronic HIV (CHI), inflammatory and patrolling monocytes express reduced CX3CR1 density compared to uninfected (HIV-) controls. In addition, CX3CR1 on microglia has been reported to have neuromodulatory effects in the brain. We investigated the dynamics of CX3CR1 density on monocyte subpopulations in individuals who initiate combination antiretroviral therapy (cART) during acute HIV infection (AHI) and assessed the relationship with central nervous system (CNS) outcomes. Methods: We examined 18 AHI adults (n=10 Fiebig stage (F)I/II and n=8 FIII) who initiated cART. As controls CHI adults (n=27 pre-cART; n=30 and n=19 at 24 and 48 weeks post-cART, respectively) and demographically matched HIV- adults (n=13) were included. CX3CR1 density (geometric mean fluorescence intensity [GMFI]) was measured on monocytes (classical and CD16+ inflammatory and patrolling subsets) from peripheral blood mononuclear cells by multiparametric flow cytometry using a protocol capturing maximal chemokine receptor recycling and expression. Neuropsychological (NP) tests performed included Trail Making A, Color Trails 1 and 2, and Grooved Pegboard to compute a summary NPZ-4. Nonparametric statistics were used. Results: The median age was 30, 33, and 31 years for AHI, CHI and HIV-, respectively. 61% of HIV+ and 67% of HIV- were male. In CHI at baseline, CX3CR1 density on inflammatory monocytes was lower compared to HIV- and AHI (p’s<0.001). Despite up to 48 weeks of cART, CX3CR1 density did not normalize to HIV- levels (p’s<0.0001) and residual CX3CR1 monocyte density correlated with worse NP testing scores (global NPZ; rho=-0.308, p=0.038 and rho=-0.486, p=0.035 for 24 and 48 weeks post-cART, respectively). At baseline, CX3CR1 density on inflammatory monocytes in AHI was lower than in HIV- (p’s<0.01). However post-cART, CX3CR1 levels normalized and unlike in CHI, were not associated with NP test scores. While differential CX3CR1 densities on classical and patrolling monocytes were noted between AHI, CHI and HIV- at baseline and post-cART, these subsets were not associated with either global or subdomain NP test scores. Conclusion: Unlike in treated CHI, early cART instituted in AHI restores perturbed CX3CR1 density on inflammatory monocytes. This may halt a detrimental cascade initiated by monocyte trafficking to the CNS that is linked to cognitive decline. These data reveal the benefits of initiation of cART early during infection.

Poster Abstracts

445 ART IN EARLY INFECTION IMPROVES NEUROCOGNITION REGARDLESS OF INFECTION DURATION Kevin Robertson 1 , Javier R. Lama 2 , Peter Brandes 2 , Eduardo Ruiz 2 , Cecilia Correa 2 , Eline Appelmans 3 , Siavash Pasalar 3 , Lindsay Haselden 3 , Rachel A. Bender Ignacio 4 , Serena S. Spudich 5 , Christopher D. Pilcher 6 , Ann Duerr 3 , for the SABES team

444 EARLY ART IN ACUTE HIV LIMITS DETRIMENTAL CX3CR1 MONOCYTES LINKED TO CNS DYSFUNCTION Michelle L. D’Antoni 1 , Phillip Chan 2 , Danielle M. Clements 1 , Yotin Chinvarun 2 , Vedbar S. Khadka 1 , Somporn Tipsuk 2 , Robert Paul 3 , Nitiya Chomchey 2 , Donn J. Colby 2 , Jintanat Ananworanich 4 , Robert Gramzinski 4 , Serena S. Spudich 5 , Lishomwa C. Ndhlovu 1 , for the RV254/SEARCH010; SEARCH013 and SEARCH011 study groups

CROI 2019 161