CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

626 VACS INDEX IS SUPERIOR TO NADIR CD4 COUNT FOR PREDICTING AMI AND MORTALITY Christopher Rentsch 1 , Janet Tate 1 , Vincent C. Marconi 2 , Matthew Budoff 3 , Adeel A. Butt 4 , Matthew Freiberg 5 , Matthew Goetz 6 , Maria Rodriguez-Barradas 7 , David Rimland 8 , Amy Justice 9 1 VA Connecticut Hlthcare System, West Haven, CT, USA, 2 Emory Univ, Atlanta, GA, USA, 3 Harbor–UCLA Med Cntr, Torrance, CA, USA, 4 Weill Cornell Med Coll, New York, NY, USA, 5 Vanderbilt Univ, Nashville, TN, USA, 6 VA Greater Los Angeles Hlth Care System, Los Angeles, CA, USA, 7 Baylor Coll of Med, Houston, TX, USA, 8 Atlanta VA Med Cntr, Decatur, GA, USA, 9 VA Connecticut Hlthcare System, West Haven, CT, USA Background: After adjustment for cardiovascular risk factors and despite higher mortality, HIV remains independently associated with a higher risk of acute myocardial infarction (AMI). Among HIV+ patients, time-updated Veterans Aging Cohort Study (VACS) index is superior in predicting incident AMI and mortality over baseline, time-updated, and cumulative measures of HIV-1 RNA and CD4 count. Nadir CD4 count has also been shown to be independently associated with incident AMI after controlling for other cardiovascular risk factors. We compare the associations between nadir CD4 count and time-updated VACS Index on AMI incidence and all-cause mortality. Methods: We included HIV+ patients starting combination antiretroviral therapy (cART) in VACS from 1996–2012. Patients were followed from cART initiation until AMI, death, last clinic visit or 9/30/2012. Primary outcomes were incident AMI (Medicaid, Medicare and Veterans Affairs ICD-9 codes) and all-cause mortality. For each outcome we fitted adjusted proportional hazards models for nadir CD4 count and time-updated VACS Index, for each exposure separately and a combined model including both exposures to assess independent effects. The Akaike information criterion (AIC) was used to assess model fit (lower AIC = better model fit). Results: 8,168 HIV+ (55,263 person-years) were analyzed with 196 incident AMIs and 1,711 deaths. Adjusting for known cardiovascular risk factors, nadir CD4 count predicted mortality, and time-updated VACS Index predicted both AMI and mortality. Nadir CD4 count <50 was associated with a HR of 0.69 (95% CI: 0.31-1.54) for AMI and a HR of 3.17 (95% CI: 2.09-4.81) for mortality. Time-updated VACS Index score of 55+ was associated with a HR of 3.36 (95% CI: 2.14-5.28) for AMI and a HR of 32.02 (95% CI: 26.40-38.85) for mortality. Time-updated VACS Index had the lowest AIC for both outcomes and was not substantively lower with addition of nadir CD4. After adjusting for time-updated VACS Index, nadir CD4 count <50 was no longer associated with mortality (HR 0.69, 95% CI: 0.45-1.05). Conclusion: Time-updated VACS Index predicted both AMI and mortality and nadir CD4 count was predictive of mortality. When both were entered in a single model, nadir CD4 count was no longer predictive of either event. These findings suggest that current health determines risk more than prior history and that risk assessment can be improved by biomarkers of organ injury. 627 EPICARDIAL FAT, IMMUNE ACTIVATION, AND CORONARY PLAQUE AMONG HIV+ AND HIV- WOMEN Suman Srinivasa 1 , Michael Lu 1 , Kathleen V. Fitch 1 , Travis R. Hallett 1 , Tricia H. Burdo 2 , Janet Lo 1 , Sara E. Looby 1 , Udo Hoffmann 1 , Steven K. Grinspoon 1 , Markella V. Zanni 1 1 Massachusetts General Hosp, Boston, MA, USA, 2 Temple Univ, Philadelphia, PA, USA Background: Mechanisms underlying the three-fold increased risk of myocardial infarction among HIV-infected vs. non-HIV-infected women remain unclear. HIV infection and/ or treatment predisposes to deposition of ectopic fat, and ectopic fat depots are known to release immunomodulatory cytokines relevant to atherogenesis. No prior studies have explored the epicardial fat depot in relation to immune activation and subclinical coronary atherosclerotic plaque among HIV-infected and non-HIV-infected women. Methods: 55 HIV-infected and 27 non-HIV-infected women without known cardiovascular disease who previously underwent coronary CT angiography (CCTA) and metabolic/ immune phenotyping were included. Epicardial adipose tissue (EAT) volume was derived from CT and related to systemic markers of immune activation and arterial inflammation, in addition to extent and composition of subclinical coronary atherosclerotic plaque. ANOVA and the Kruskal-Wallis test were performed to investigate trends among groups stratified by HIV serostatus and high/low EAT (defined in reference to median EAT for each serostatus group). Results: Asymptomatic HIV-infected women (mean age 47±8 years, duration HIV 15±6 years, duration ART 8±5 years, CD4+ count 599±299 cells/μl, undetectable VL 84%) and age-matched non-HIV-infected women with comparable BMI (28±5 vs. 29±5 kg/m2) had similar median volumes of EAT(54[41,79] vs. 65[41,78]mm3)(P>0.05). Markers of monocyte activation and arterial inflammation differed by [HIV serostatus/EAT volume] subgroup (sCD163 (P=0.004), sCD14 (P=0.03), CXCL10 (P=0.02), Lp-PLA2 (P=0.04)) and were highest among HIV-infected women with excess EAT as compared to HIV-infected women without excess EAT, non-HIV-infected women with excess EAT, and non-HIV- infected women without excess EAT. Notably, the percent of non-calcified coronary atherosclerotic plaque also differed by [HIV serostatus/EAT volume] subgroup (P<0.05) and was highest among HIV-infected women with excess EAT. Conclusion: Among women with HIV, excess epicardial fat is associated with immune activation and arterial inflammation, as well as non-calcified subclinical coronary atherosclerotic plaque. Future treatment strategies aimed at reducing ectopic fat among HIV-infected women may have potential to dampen systemic immune activation and favorably influence plaque morphology. 628 DIVERGENT EFFECTS OF HIV AND SMOKING ON AORTIC INFLAMMATION Chris T. Longenecker 1 , Claire E. Sullivan 2 , Justin T. Morrison 2 , Corrilynn O. Hileman 1 , David A. Zidar 1 , Robert Gilkeson 1 , James O’Donnell 1 , Grace A. McComsey 1 1 Case Western Reserve Univ, Cleveland, OH, USA, 2 Univ Hosps of Cleveland Med Cntr, Cleveland, OH, USA Background: The detrimental effects of smoking on cardiovascular disease (CVD) and mortality in patients with and without HIV may be mediated in part by systemic and tissue- specific inflammation. Methods: We prospectively studied 55 HIV+ subjects on stable antiretroviral therapy and 19 age-matched HIV-uninfected controls without known CVD who underwent 18flurodeoxyglucose positron emission tomography (FDG-PET). Aortic target-to-background ratio (TBR) and spleen standardized uptake values (SUV) measured 2-hours post-FDG were the primary outcomes of interest. We used hierarchical linear and logistic regression to examine the association of HIV and smoking status with PET variables. We additionally explored relationships of PET variables with biomarkers of inflammation, monocyte activation, and coronary calcification after adjustment for HIV, smoking, and other traditional CVD risk factors.

Poster and Themed Discussion Abstracts

CROI 2017 268