CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: Overall, mean (SD) age was 48(11) years; 81%were male and 54%were current smokers [median 0.5 packs per day, 25 pack-years]. HIV+ and HIV-neg groups were well-matched for demographics and clinical variables (p>0.2) except HIV+ were more likely to be African American (73 vs. 47%) and to have hypertension (56 vs. 16%). For HIV+, median CD4+ was 690 cells/ml and 88% had HIV-1 RNA <20c/ml; 43%were on a protease inhibitor. In fully-adjusted models (see Figure), HIV was associated with 0.15 (95%CI 0.04-0.27; p=0.01) higher aortic TBR while current smoking was marginally associated with a lower TBR [-0.11 (95%CI -0.22 to 0.01); p=0.07]. Spleen SUV was not associated with either HIV or smoking in unadjusted or adjusted models. There was no evidence for an HIV*smoking interaction for aortic TBR or spleen SUV models (all p>0.1). In unadjusted models, spleen SUV was associated with presence of coronary calcification [OR per 1 standard deviation increase in SUV 1.7 (95%CI 1.0-2.9), p=0.047], but this was attenuated in fully adjusted models (p=0.15). Soluble CD163 was positively associated with spleen SUV in fully adjusted models (p=0.05), but not with aortic TBR (p=0.9). Conclusion: To our knowledge, this is the largest sample of HIV+ subjects studied by PET/CT to date, allowing us to explore important relationships with traditional and non- traditional risk factors. As measured by aortic FDG uptake, HIV is associated with increased aortic inflammation independent of traditional risk factors. In contrast, current smoking is marginally associated with lower aortic inflammation. 629 CRP PREDICTS SUBCLINICAL CVD PROGRESSION IN HIV- BUT NOT HIV+WOMEN Caitlin A. Moran 1 , Aswani Vunnava 1 , Anandi N. Sheth 1 , Christina Mehta 1 , Phyllis Tien 2 , Michael Plankey 3 , Elizabeth T. Golub 4 , Arshed Quyyumi 1 , Robert C. Kaplan 5 , Igho Ofotokun 1 1 Emory Univ, Atlanta, GA, USA, 2 Univ of California San Francisco, San Francsico, CA, USA, 3 Georgetown Univ, Washington, DC, USA, 4 The Johns Hopkins Univ, Baltimore, MD, USA, 5 Albert Einstein Coll of Med, Bronx, NY, USA Background: HIV infection is associated with an increased risk of early cardiovascular disease (CVD), but identifying those with HIV who would benefit from targeted CVD risk modification remains challenging. Biomarkers including C-reactive protein (CRP) improve CVD event prediction in the general population, but their use in the HIV population is less clear. We assessed the association of CRP with subclinical CVD progression among women enrolled in the Women’s Interagency HIV Study (WIHS). Methods: Retrospective analysis of the WIHS cardiovascular substudy, in which B-mode carotid artery (CA) ultrasound was performed at baseline (BL) and at 1-3 follow-up visits from 2004-2013 to assess CA plaques and common carotid artery intima-media thickness (CIMT). High sensitivity (hs) CRP was measured previously from plasma obtained at BL. We used multivariable logistic and linear regression models stratified by HIV serostatus to determine the association of BL hsCRP with CA plaque and CIMT progression, defined as increases in plaque number and in CIMT between BL and final visits, adjusting for traditional CVD risk factors. Results: 783 women [572 HIV(+), 211 HIV(-), 62% Black, 29% Hispanic, median age 41 (IQR 35-47) years] were followed for a median 6.6 (IQR 6.4-7.0) years. Among HIV(+) participants, median CD4 was 452 (IQR 288-658) cells/mm3 and 46% had HIV RNA <80 cop/mL at BL. BL median (IQR) 10-year Framingham risk score was 8 (3-12) in HIV(+) vs. 9 (3-13) in HIV(-), p=0.43). BL median (IQR) hsCRP was 2.2 (0.8-5.3) mg/L in HIV(+) and 3.2 (0.9-7.7) mg/L in HIV(-) women (p=0.005). Unadjusted CA plaque progression occurred in 65 (12%) vs. 15 (8%) of HIV(+) and HIV(-) women, respectively. Mean (SD) CIMT change was 25 (47) μm in HIV(+) women and 26 (62) μm in HIV(-) women. The adjusted odds of CA plaque progression in HIV(+) women were 0.99 (95%CI 0.77-1.28) per unit increase of hsCRP (p=0.94) and 3.74 (95%CI 1.34-10.24) in HIV(-) women (p=0.01). The adjusted mean difference in CIMT change per unit increase in hsCRP among HIV(+) women was 3.0 μm (95%CI -1.5-7.5, p=0.20) and 5.4 μm (95%CI 0.2-10.7, p=0.04) in HIV(-) women. Conclusion: HsCRP was associated with progression of CA plaques and CIMT in HIV(-), but not HIV(+), women despite similar BL CVD risk, suggesting that the pathogenesis and therefore the biomarkers associated with subclinical CVD may be different in the setting of HIV infection. Additional studies of CVD pathogenesis in the HIV population are warranted to aid targeted CVD risk modification. 630 SERUM ST2 IS AN INDEPENDENT PREDICTOR OF ALL-CAUSE MORTALITY IN HIV-INFECTED PATIENTS Rodolphe Thiébaut 1 , Sophie Hue 2 , Fabien LeMarec 1 , Jean Daniel Lelievre 2 , Michel Dupon 3 , Emile Foucat 2 , Isabelle Pellegrin 3 , Christine Lacabaratz 2 , Fabrice Bonnet 3 , Yves Levy 2 1 INSERM, Bordeaux, France, 2 INSERM, Créteil, France, 3 CHU de Bordeaux, Bordeaux, France Background: Soluble Suppression of Tumorigenicity 2 (sST2) is a decoy receptor of IL-33. The IL-33/ST2 axis is involved in several inflammatory and immune diseases. The predictive value of sST2 for death in HIV infection is unknown. Methods: Patients enrolled in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients, who had a plasma sample available in the bio-bank were systematically eligible. sST2 and sCD14 were measured using Luminex® multiplex bead-based technology (R&D Systems) and a Bio-Plex 200 instrument (BioRad). Mean coefficient of variation was <12% for sST2 and <14% for sCD14. A good correlation between ELISA and Luminex technology was observed. Predictive capacities of sST2, sCD14 and of the Veteran Aging Cohort Study (VACS) clinical score at baseline on overall mortality were compared using multivariable Cox proportional hazards models adjusted for sex, age, tobacco consumption, anemia, duration of viral load > 500 cp/mL, low glomerular filtration, history of diabetes or cancer and hepatitis B virus infection. Results: During a median follow-up of 7.2 years (IQR: 6.0; 7.9), 93 deaths from all causes (incidence rate 9.9 per 1000 patient-years; 95% confidence interval 7.9; 11.9) were reported in 1,414 patients with median baseline CD4+ cell count of 742 cells/mm3 (inter-quartile range [IQR]: 545; 970). The median sST2 baseline concentration was 22.9 ng/mL (IQR: 17.7; 30.3) and was higher (30.8 ng/mL, IQR: 21.5; 42.1) in patients who died as compared to those who stayed alive (22.6 ng/mL; IQR: 17.5; 29.6) (p<10-4). An increased risk of death of 2% for a concentration 1.0 ng/mL higher of sST2 remained after adjustment for sCD14 and VACS score (adjusted hazard ratio: 1.02; p<10-4). Compared to those with <17.7 ng/mL (first quartile), patients with >30.3 ng/mL (fourth quartile) had a three-fold higher probability of dying during follow-up (HR=3.31, 95% CI [1.53; 7.15], p<10-3). The predictive capacity of sST2 was confirmed in a validation cohort (n=246, 15 deaths) with an improved area under the curve from 0.708 without sST2 to 0.724 with sST2. Conclusion: sST2 is a new valuable biomarker to evaluate the risk of all-cause mortality in HIV disease. These results validate sST2/IL-33 as an emerging key pathway that could be involved in systemic disease including HIV infection. 631 A LOWER CD COUNT PREDICTS MOST CAUSES OF DEATH EXCEPT CARDIOVASCULAR DEATHS Gisela Leierer 1 , Armin Rieger 2 , Brigitte Schmied 3 , Mario Sarcletti 1 , Maria Geit 4 , Bernhard Haas 5 , Ninon Taylor 6 , Michaela Rappold 1 , Bruno Ledergerber 7 , Robert Zangerle 1 1 Med Univ of Innsbruck, Innsbruck, Austria, 2 Med Univ of Vienna, Vienna, Austria, 3 Otto-Wagner Hosp, Vienna, Austria, 4 Kepler Univ Hosp Linz, Linz, Austria, 5 General Hosp Graz South-West, Graz, Austria, 6 Paracelsus Med Univ, Salzburg, Austria, 7 Univ of Zurich, Zurich, Switzerland Background: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: period 1: 1997-2000; period 2: 2001-2004; period 3: 2005-2008; period 4: 2009-2011; and period 5: 2012-2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm³. Vital status of patients was cross-checked with death registry data. Results: Of 6852 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and Non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5, respectively) and deaths due to Non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm³, lower CD4 counts conferred a higher risk of deaths due to AIDS- related diseases, liver-related diseases, Non-AIDS infections and Non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality (Fig. 1). Results were similar in sensitivity analyses where observation time was divided into 2 periods: 1997-2004 and 2005-2014.

Poster and Themed Discussion Abstracts

CROI 2017 269