CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Results: All pts and C were MSMwith median age of 40.5 [31-51] (pts) and 38 [33-47] (C); p=0.674, and CD4 count of 431[272-559] pts and 958 [741- 1273] (C); p<0.001. Baseline HIV load was 40,500[19,750-84,250]. Pts’ 1 yr CD4 742[600-849] and all HIV load <20 cp/mL. CAWwas thicker in pts vs C [57% vs 52% p=0.001]. CAWT correlated with gut IHC CD8+ T-cell density (SrC=0.701;p=0.019), but not gut CD4+T-cell IHC or any PBMC T cells or subpopulations. CAWC fat proportion was lower in HIV+ (14% vs 21%;p=0.012) and Ca proportion was higher in pts (28% vs 23%; p=0.05) than C. No differences were found in the non-fat-non-calcium proportion. Gut IHC CD8 T-cell density positively correlated with CAWC Ca (SrC 0.542;p=0.05) and negatively with fat CAWC (SrC=-0.612;p=0.021). Soluble (s) CD163 positively correlated with fat CAWC (SrC=0.651;p=0.008) and negatively correlated with sMAdCAM-1 (SrC -0.610;p=0.023) and intestinal fatty acid binding protein (SrC -0.657;p=0.01). Conclusion: While CA thickness and calciumwere higher in people with greater gut CD8 T-cell density, fat content was lower. Lower monocyte activation also correlated with less fat content yet more gut homing and intestinal turnover. Thus, gut repair may be essential for modulating the monocyte activation associated with fat infiltration of coronary arteries. 635 CONTRIBUTION OF HUMAN HERPESVIRUS 8 AND HERPES SIMPLEX 2 TO PROGRESSION OF IMT IN HIV Fernando Lidón , Sergio Padilla, José A. García, Marta Fernández, Javier García-Abellán, Victoria Ortiz de la Tabla, Félix Gutiérrez, Maria Del Mar Masia, for the Elche Hospital General Universitario de Elche, Elche, Spain Background: Several herpesviruses have been implicated in the pathogenesis of atherosclerosis, but limited information is available about their role in the progression of atherosclerosis in people living with HIV (PLWH). Human herpesvirus 8 (HHV-8) is a lymphotropic and vasculotropic herpesvirus with potential pro-atherogenic effects. However, to date no clinical studies have associated HHV-8 infection with atherosclerotic disease. We explored the influence of coinfection with HHV-8 and other herpesviruses on the rate of progression of subclinical atherosclerosis in virologically-suppresed PLWH. Methods: Prospective study including men who have sex with men (MSM) infected with HIV. At the baseline visit, IgG antibodies against HHV-8 and other herpesviruses, highly-sensitive C-reactive protein (hsCRP) levels, and the Framingham risk score were measured. To evaluate the progression of subclinical atherosclerosis, successive carotid intima-media thickness (cIMT) measurements with high-resolution carotid artery ultrasound were performed over an eight-year period. Adjusted general linear mixed models were used to assess factors associated with faster cIMT progression. Results: 141 participants with suppressed HIV-RNA (<200 copies/ml) at cIMT measurement during the study period were included. 46 (31.3%) were coinfected with HHV-8 and 76 (54%) with herpes-simplex virus-2 (HSV-2). Factors associated with faster cIMT progression adjusting for CD4 cell counts, time between cIMT measurements, hepatitis C, varicella-zoster virus and cytomegalovirus coinfection were seropositivity for HHV-8 (p=0.055), HSV- 2+HHV-8 coinfection (p=0.028), the Framingham risk score (p=0.045) and hsCRP (p=0.023). Coinfection with HHV-8 was independently associated with higher levels of hsCRP (OR 1.09 [95% CI, 1.02-1.17], p=0.016). When hsCRP and HHV-8 were simultaneously included in the adjusted model, the relationship of HHV-8 with cIMT progression was attenuated. Conclusion: HHV-8 contributes to progression of cIMT with a more prominent role when it coinfects with HHV-2 in virologically-suppressed PLWH, and this effect could be driven by systemic inflammation 636 HIV INFECTION AND RISK OF RECURRENT VENOUS THROMBOEMBOLISM: A NATIONAL COHORT STUDY Casper Rokx 1 , Jaime Borjas Howard 2 , Colette Smit 3 , Ferdinand Wit 4 , Elise D. Pieterman 1 , Suzanne Cannegieter 5 , Willem Lijfering 5 , Karina Meijer 2 , Peter Reiss 3 , Wouter Bierman 2 , Vladimir Tichelaar 2 , Bart Rijnders 1 1 Erasmus University Medical Center, Rotterdam, Netherlands, 2 University Medical Center Groningen, Groningen, Netherlands, 3 Stichting HIV Monitoring, Amsterdam, Netherlands, 4 Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands, 5 Leiden University Medical Center, Leiden, Netherlands Background: People with HIV (PWH) are at increased risk of a first venous thrombotic event (VTE). Whether this also translates into more recurrent VTE is

unknown. We assessed VTE recurrence rates in PWH and compared these to VTE recurrence rates in HIV uninfected patients. Methods: PWH with a first VTE between 2003-2018 were identified in the ATHENA cohort and compared to HIV uninfected patients with a first VTE in the MEGA cohort in the Netherlands. Provoked VTE were associated with cancer, major surgery, estrogen exposure, immobilization, or plaster cast use for fractures. The primary endpoint was recurrence of VTE following discontinuation of anticoagulant therapy for a first VTE. Multivariable Cox regression was used to estimate the VTE recurrence risk. Kaplan-Meier estimates (KME) of VTE recurrence accounted for death as competing risk and were stratified for provoked or unprovoked first VTE. Results: Of 201 PWH with a first VTE in ATHENA, 153 had observations after anticoagulant therapy withdrawal. Of these, 126 (95 unprovoked) were in men and 27 events (13 unprovoked) in women. In MEGA, 4005 patients had a first VTE, including 1813 (998 unprovoked) in men and 2192 (363 unprovoked) in women. In PWH, 40 recurrent VTE occurred during 772 person years of follow up (PYFU; median 4.7 years, 5.2/100 PYFU, 95%CI 3.8-7.0). In MEGA, 635 recurrent VTE occurred during 20,215 PYFU (median 6.1 years, 3.1/100 PYFU, 95%CI 2.9-3.4). KME were higher for PWH at 1 year following anticoagulant withdrawal (13% vs 6%), attenuating at 3 (20% vs 11%) and 5 (23% vs 15%) years of follow up. PWH were at higher risk of recurrent VTE during the first year following anticoagulant withdrawal (HR 1.86, 95%CI 1.16-3.01), but not thereafter (HR 1.06, 95%CI 0.65-1.73). KME at 1, 3 and 5 years in PWH and HIV uninfected patients with unprovoked first VTE were 16% vs 9%, 24% vs 17% and 27% vs 24%. Multivariable Cox regression showed that the CD4+ T-cell increase between the first VTE and anticoagulant therapy discontinuation was an independent predictor of a lower recurrent VTE risk (HR 0.73 per 100 CD4+ T-cells increase, 95%CI 0.60-0.89). Conclusion: PWH were at increased risk of recurrent VTE, which might be driven by HIV-related immune deficiency, inflammation, and associated hypercoagulability. The increased risk attenuated over time, possibly reflecting the gradual recovery of these factors following initiation of effective antiretroviral therapy. 637 PREDISPOSING FACTORS FOR VENOUS THROMBOEMBOLISM IN HIV- INFECTED PATIENTS Mark W. Tenforde 1 , Robin M. Nance 1 , Susan Heckbert 1 , Kristina Crothers 1 , Matthew Budoff 2 , W. C. Mathews 3 , Joseph J. Eron 4 , Richard D. Moore 5 , Michael J. Mugavero 6 , James Willig 6 , Greer Burkholder 6 , Mari Kitahata 1 , Joseph Delaney 1 , Heidi M. Crane 1 , for the Centers for AIDS Research Network of Clinical Information Systems 1 University of Washington, Seattle, WA, USA, 2 University of California Los Angeles, Los Angeles, CA, USA, 3 University of California San Diego, San Diego, CA, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 6 University of Alabama at Birmingham, Birmingham, AL, USA Background: HIV is associated with chronic inflammation and immune activation and increases the risk of venous thromboembolism (VTE) events. Predisposing factors are important in the epidemiology of VTE in the general population but little is known about their presence among people living with HIV (PLWH) in the era of widespread access to antiretroviral therapy. Methods: We included PLWH with VTE in 2005-2017 at 6 sites in the CNICS cohort. We developed a centralized adjudication approach for VTEs with ascertainment based on multiple criteria including diagnoses and procedures, followed by centralized adjudication of primary data by two expert reviewers, and a third reviewer if discrepancies occurred. VTEs were classified by type and anatomic location. Reviewers identified the presence of pre-disposing factors such as bedrest and long plane rides. This analysis included only initial VTEs for those with recurrent events. Results: We included 318 PLWH with VTE: 181 (57%) deep venous thrombosis (DVT), 139 (44%) pulmonary embolus (PE), and 38 (12%) catheter-associated thrombosis events, including 40 (13%) with multiple types simultaneously (mostly DVT/PE). Two-hundred forty-eight (78%) patients were male; median age was 49 years old (interquartile range [IQR]: 40,55); and 134 (42%) were white, 151 (47%) black, and 26 (8%) Hispanic. Median CD4 count was 312 cells/ µL (IQR: 149,548) and 31% had a detectable viral load (≥400 copies/mL). One- hundred forty-four (45%) were current smokers. Most patients had multiple predisposing factors (Table); mean 2.3 (standard deviation [SD] 1.5). Only 33 (10%) had no pre-disposing factor identified. The most common predisposing

Poster Abstracts

CROI 2019 241