CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: We conducted a case-control study nested in the CFAR Network of Integrated Clinical Systems cohort, comparing adjudicated cases with an ischemic stroke or primary (type 1) MI after ≥6 months of ART to controls matched on regimen and time since ART initiation. Biomarkers including angiopoietin 1, angiopoietin 2 (ANG-2), plasminogen activation inhibitor 1, serum amyloid A, interleukin 6 (IL-6), C-reactive protein (CRP), and soluble vascular cell adhesion molecule 1, intercellular adhesion molecule 1, P-selectin, and CD14 were measured in stored plasma. Conditional logistic regression identified biomarkers associated with stroke or MI status, with and without adjustment for potential confounders including age, race, sex, diabetes, tobacco use, hypertension, and statin use. Biomarkers were log-transformed. Odds ratios (OR) represent the odds of a stroke or MI for each log increase in biomarker level. Results: Among 42 stroke cases and 83 matched controls, 76.2% and 88.0% had viral load <400 copies/mL, respectively (χ2 p=0.09). In bivariable analyses, ANG-2 was the only biomarker associated with stroke (OR 2.02, 95% confidence interval [CI] 1.03-3.97). In multivariable modeling, ANG-2 remained associated with stroke (adjusted OR 2.22, 95% CI 1.05-4.67). Among 69 MI cases and 138 matched controls, 82.6% and 77.5% had viral load <400 copies/mL, respectively (χ2 p=0.40). In bivariable analyses, ANG-2 (OR 1.84, 95% CI 1.09-3.13), IL-6 (OR 1.49, 95% CI 1.01-2.20), and CRP (OR 1.25, 95% CI 1.05-1.49) were each associated with MI. In multivariable models ANG-2 remained associated (aOR 1.73, 95% CI 1.01-2.95), CRP had a borderline association (aOR 1.22, 95% CI 0.98- 1.51), and IL-6 had no association with MI. Conclusion: ANG-2 levels were elevated in treated HIV-infected individuals in the 12 months prior to an ischemic stroke or primary MI, compared to treated HIV-infected controls. Because ANG-2 is a potential target for therapeutic intervention, additional study of its role in HIV-associated cardiovascular disease and related therapeutic interventions is warranted. 415 HAND IMPROVEMENT IS ASSOCIATED WITH INCREASED CPE SCORE AFTER ARV INTENSIFICATION Gilles Force 1 , Idir Ghout 2 , Elodie Bouaziz-Amar 2 , Karim Dorgham 2 , Dhiba Marigot-Outtandy 2 , Didier Troisvallets 3 , Valerie Hahn 4 , Helene Defferriere 2 , Natacha Darchy 1 , Jacques Ropers 2 , Jean-Louis Laplanche 2 , Constance Delaugerre 2 , Gilles Peytavin 2 , Guislaine Carcelain 2 , Pierre de Truchis 2 1 Institut Hospitalier Franco-Britannique, Levallois-Perret, France, 2 AP–HP, Paris, France, 3 Centre Hospitalier de Gonesse, Gonesse, France, 4 Centre Hospitalier Sainte Anne, Paris, France Background: Neuro+3 is a pilot open-label prospective study of ARV intensification in controlled patients (pts) with HAND. Initial treatment was switched for a new combination with better CPE score (∆CPE ≥+3 for total score ≥9) and same cognitive tests were assessed at W48 and W96. Methods: Among 63 screened pts, 31pts with HAND were included with at least 2 ability domains >1SD for the following tests and Beck Depression Inventory BDI II assessment: Grooved Pegboard (d and nd), Verbal Fluency, CVLT, Digit span, PASAT, Digit symbol, WCST (6 domains). Primary objective was to demonstrate improvement in Global Deficit Score (GDS) and HAND classification (HC), with ITT and PerProtocol analysis with updated 2016 genotype algorithm. Plasma and CSF virological and immunological assessment, neopterin and NFL, were followed. Results: Initial median CPE score of 6 increased to 10 after intensification (MVC addition 10pts, add or switch InSTI 21pts, NNRTI 6pts, DRV/r 6pts, ABC 4pts). Median GDS improved from 1.4 at baseline to 0.8 at W48 (p=0.012) and 1.0 at W96 (p=0.009); HC (16 HAD, 8 MND, 7 ANI) became at W48 (8, 5, 11, and 7 pts with only one altered domain)(p=0.002) and at W96 (6, 3, 17, 2, and 3 pts with normal tests)(p<0.001). At W96 we observed both GDS improvement (GI) (GDS reduction ≥0.2) and HC improvement in 12 pts (39%) and improvement of one of the items (GI or HC) in 13 pts (42%). Lowest CPE score at baseline was predictive for GI at W48 (rho=0.5;p=0.017). In comparison with improved GDS group (19 pts), failing GDS group (12 pts) at W96 had more frequently positive CSF VL 67% vs 26% (p=0.084), had bad evolution for ∆BDI score -0.5 vs -6 (p=0.024), had lesser ∆CPE 2016 score +3 vs +4 (p=0.041), had persistent inflammation in plasma with ∆neopterin +1.9 vs -0.4 (p=0.028). Enhanced CPE 2016 score was predictive for GI at W48 (rho=-0.46;p=0.03): no GI if ∆CPE ≤+2, 50%with ∆CPE +3, 67%with +4, and 83% if ≥+5. We compared the 22 patients with enhanced CPE 2016 score vs the 9 others, and ∆GDS was -0.4 vs +0 (p=0.018), ∆BDI score -5 vs +1 (p=0.029). No correlation was found between

VasR: overweight 26.4%, obesity 4.8%, HT 18.7%, DB 7.3%, DL 28%, current smoking 29%, prior cerebro/cardiovascular event 2.7%. When excluding pts with confounding factors, HAND was limited to 825 out of 2656 evaluations (24%): Asymptomatic Neurocognitive Impairment 12%, Mild Neurocognitive Disorder 9.7%, HIV-Associated Dementia 2.4%. Among factors associated to HAND, the risk was increased with DB and HCV+, and reduced with overweight (Table 1). Conclusion: Diabetes and HCV coinfection, both characterized by a pro- inflammatory status and linked to accelerated vascular disease, are strong risk factors of HAND. Being overweight, a proxy of better medical and nutritional care and a measure of generalized rather than central obesity, seems to have a protective role on cognition. Traditional vascular risk-reduction strategies and HCV cure could improve neurocognitive performance in HIV+ persons.

Poster Abstracts

414 ENDOTHELIAL ACTIVATION IN HIV-ASSOCIATED ISCHEMIC STROKE AND MYOCARDIAL INFARCTION Susan M. Graham 1 , Susanna Harju-Baker 1 , Junmei Chen 2 , Jennie Le 2 , Dominic W. Chung 2 , Mark M. Wurfel 1 , Yu Ni 1 , Robin M. Nance 1 , Peter W. Hunt 3 , David Tirschwell 1 , Alice S. Ryan 4 , Jeffrey N. Martin 3 , Heidi M. Crane 1 , Jose A. Lopez 2 , W. C. Liles 1 1 University of Washington, Seattle, WA, USA, 2 Bloodworks Northwest Research Institute, Seattle, WA, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 University of Maryland, Baltimore, MD, USA Background: HIV infection, whether treated or untreated, leads to endothelial activation, which promotes platelet adhesion and accelerates atherosclerosis. We determined whether key biomarkers were elevated in individuals on antiretroviral therapy (ART) in the 12 months before an ischemic stroke or primary myocardial infarction (MI), relative to biomarker levels in matched controls who experienced no stroke or MI.

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