CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

C.I.=0.53,3.70; Hispanic/other: RR=1.66, 95% C.I.=0.42,6.46; interaction p-value=0.18). Disability was not associated with CVE (RR= 1.54; 95% CI =0.78,3.05). Sixty-eight incident cases of DM occurred. Disability was associated with incident DM (RR=2.03 [95% C.I.=1.17,3.54]); this association did not vary by race. Being pre-frail/frail was not associated with incident diabetes (RR= 1.45, 95% C.I.= 0.90,2.34). There was no effect modification by sex or age on associations between either disability or frailty and DM and CVE. Conclusion: Within our cohort of aging HIV+ participants, frailty and disability were common and associated with significantly elevated risk for CVE and DM, respectively. While the association between frailty and CVE was only apparent among black persons, the disability/DM association existed across demographics. Routinely assessing functional status in aging HIV+ persons may optimize risk stratification for serious co-morbid conditions. 677LB CHANGE IN SOLUBLE GLYCOPROTEIN VI (SGPVI) WHEN SWITCHING FROM ABC/3TC TO TAF/FTC Patrick W. Mallon 1 , Robert T. Maughan 1 , Alejandro A. Garcia 1 , Willard Tinago 1 , Aoife Lacey 1 , Andrew Lovell 2 , Eimear Dunne 3 , Elena Alvarez-Barco 1 , Alan Winston 2 , Frank Post 4 , Dermot Kenny 3 , Mingjin Yan 5 , Moupali Das 5 , Martin Rhee 5 1 University College Dublin, Dublin, Ireland, 2 Imperial College London, London, UK, 3 Royal College of Surgeons in Ireland, Dublin, Ireland, 4 King’s College Hospital NHS Foundation Trust, London, UK, 5 Gilead Sciences, Inc, Foster City, CA, USA Background: Exposure to abacavir (ABC) has been associated with increased risk of cardiovascular events with altered platelet function implicated. Glycoprotein VI (GPVI), expressed on and shed from platelets, regulates platelet activation in response to collagen exposure. We previously demonstrated increases in soluble GPVI (sGPVI) in virologically-suppressed people with HIV-1 (PWH) switching from ABC to tenofovir disoproxil fumarate (TDF) and recently showed decreased platelet reactivity in response to collagen and increases in GPVI expression on platelets upon switching from ABC / lamivudine (ABC/3TC) to tenofovir alafenamide / emtricitabine (TAF/FTC). Changes in sGPVI when switching from ABC/3TC to TAF/FTC have not been determined. Methods: In a platelet function substudy within a randomized, double- blind, active-controlled trial of virologically suppressed PWH on ABC/3TC who were randomized to switch to TAF/FTC or remain on ABC/3TC, we quantified sGPVI in platelet-poor plasma taken at weeks 0, 4, 12, 24 and 48 by electrochemiluminescence. The primary endpoint was change in sGPVI to week 48 with the between-group difference compared using mixed effects models with repeated measures. Results: Of 556 subjects enrolled in the study, 545 (98%) had samples available for analysis. Mean (SD) age was 51 (9.3) years, 82%male, 72%white. Baseline CD4+ count was 712 (284) cells/mm 3 and 99% had HIV-1 RNA <50 copies/ml. Baseline sGPVI (µg/mL, median [IQR]) were similar between groups: TAF/FTC 7.36 (5.2, 12.7) versus ABC/3TC 8.46 (5.27, 14.51), P=0.18. The TAF/FTC group had a significantly greater increase in sGPVI to week 48 (figure), with a +14.7%, (95% CI 4.1, 26.3) difference between groups in change in sGPVI to week 48 by mixed effects models (P=0.005). Conclusion: Switching away from ABC/3TC to TAF/FTC was associated with greater increases in sGPVI. In combination with the previously demonstrated decreases in platelet reactivity and re-expression of GPVI on platelets in PWH switching from ABC/3TC to TAF/FTC, these data suggest a reversible, inherent platelet dysfunction with ABC/3TC, centered on GPVI function, which may contribute to increased risk of cardiovascular events observed in PWH exposed to ABC.

678 ELEVATED MICROPARTICLE TISSUE FACTOR ACTIVITY AND CAROTID ARTERY PLAQUE IN HIV+WOMEN Juan Lin 1 , Xiaonan Xue 1 , Kathryn Anastos 1 , Mardge H. Cohen 2 , Stephen J. Gange 3 , Jason Lazar 4 , Chenglong Liu 5 , Wendy Mack 6 , Phyllis Tien 7 , Cathy Tilley 8 , Howard Hodis 6 , Alan Landay 9 , Russell Tracy 8 , Robert C. Kaplan 1 , David B. Hanna 1 1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 Cook County Health & Hospitals System, Chicago, IL, USA, 3 The Johns Hopkins University, Baltimore, MD, USA, 4 SUNY Downstate Medical Center, Brooklyn, NY, USA, 5 Georgetown University, Washington, DC, USA, 6 University of Southern California, Los Angeles, CA, USA, 7 University of California San Francisco, San Francisco, CA, USA, 8 University of Vermont, Colchester, VT, USA, 9 Rush University Medical Center, Chicago, IL, USA Background: Expression of tissue factor (TF) on the surface of activated monocytes may trigger thrombosis, leading to clotting risk, inflammation, and atherosclerosis. TF-positive monocyte-derived microparticles (MP-TF) represent a functionally active form of TF, and its activity has been linked with poor HIV control. We hypothesized that greater MP-TF activity is associated with carotid artery plaque in HIV+ women. Methods: In our nested case-control study among HIV+ women in the Women’s Interagency HIV Study (WIHS), eligible participants underwent B-mode carotid artery ultrasound during 2 study visits occurring 7 years apart. Cases, defined as having at least 1 carotid artery plaque (focal intima-media thickness >1.5 mm) assessed at either visit, were matched 1:2 with available controls, defined as no plaque. Matching was based on age, smoking status, baseline CD4+ count, and antiretroviral therapy (ART) use. Plasma MP-TF activity was assessed by the method of Key et al.. Because the data suggested a threshold effect with case status, MP-TF levels were dichotomized at 0.537 pg/ mL, which was determined empirically after examining deciles among values above the minimum detectable limit. Conditional logistic regression estimated the association of MP-TF activity with case status, controlling for demographic and behavioral characteristics, HIV-related factors, cardiometabolic risk factors, and serum inflammation biomarkers (hsCRP, IL-6, sCD14, sCD163, Gal-3, Gal- 3BP). Results: There were 98 cases and 177 controls included (N=275): median age 46, 89% black race or Hispanic ethnicity, 51% smokers, 8% on lipid-lowering therapy, 75% on ART, 44%with undetectable HIV RNA. Mean MP-TF levels were 0.277 pg/mL (SD 0.537) in cases and 0.211 pg/mL (SD 0.719) in controls. After taking into account demographic and behavioral characteristics and HIV- related and cardiometabolic risk factors, elevated MP-TF (>0.537 pg/mL) was significantly associated with greater odds of plaque (adjusted odds ratio [aOR] 3.55, 95% CI 1.09-11.60, p=0.04). The association was attenuated after further adjustment for IL-6 but not for other biomarkers including those denoting monocyte activation (e.g., sCD14). Among those with undetectable HIV RNA (<80 copies/mL, N=121), the association was more pronounced (aOR 10.15, 95% CI 1.38-74.70, p=0.02). Conclusion: Elevated MP-TF was associated with carotid artery plaque in HIV+ women, suggesting a link between HIV infection, innate immune system perturbation, coagulation, and atherosclerosis.

Poster Abstracts

CROI 2018 252