CROI 2016 Abstract eBook

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Poster Abstracts

a median of 3 (IQR: 1-9) months. Higher levels of the inflammatory marker hsCRP, the coagulation marker D-dimer, and oxLDL predicted MI in unadjusted models (Table). hsCRP remained significantly predictive of MI after adjustment for oxLDL (aOR 1.81, P=0.021), but not after D-dimer adjustment. D-dimer and oxLDL remained independently predictive of MI in fully adjusted models. Those currently taking abacavir (n=32) had higher median D-dimer levels than those on abacavir-sparing regimens (243 vs. 203 ng/ml, P=0.04), but D-dimer remained predictive of MI even among those on abacavir-sparing regimens (OR 2.06, P=0.032). We found no evidence for a relationship between Type 1 MI risk and other markers of inflammation (IL-6, sTNFR1), myeloid activation (sCD14, sCD163), gut epithelial barrier integrity (I-FABP), interferon response (IP-10), or CMV IgG titer. Conclusions: While inflammation predicts Type 1 MI in treated HIV infection, hypercoagulability appears to be a more proximate predictor in the same pathway. OxLDL may also independently contribute to MI risk in this setting, representing a novel interventional target. Lack of an association between other markers and short-term Type 1 MI risk does not exclude a potential impact on atherosclerosis and longer-term cardiovascular outcomes.

672 Lack of Associations of Oxidized Lipoproteins With Atherosclerosis in HIV: ACTG A5260 Theodoros Kelesidis 1 ;ThuyT.Tran 2 ;ToddT. Brown 3 ; Carlee B. Moser 2 ; Heather J. Ribaudo 2 ; Michael Dube 4 ; Robert Murphy 5 ; OttoYang 1 ; Grace A. McComsey 6 ; James H. Stein 7 ; Judith S. Currier 1 1 David Geffen Sch of Med at Univ of California Los Angeles, Los Angeles, CA, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Johns Hopkins Univ, Baltimore, MD, USA; 4 Keck Sch of Med at the Univ of Southern California, Los Angeles, CA, USA; 5 Northwestern Univ, Feinberg Sch of Med, Chicago, IL, USA; 6 Case Western Reserve Univ, Cleveland, OH, USA; 7 Univ of Wisconsin-Madison, Madison, WI, USA Background: The role of oxidized lipoproteins (ox-lipids) in the pathogenesis of cardiovascular disease (CVD) in chronic HIV infection remains poorly defined. Methods: A5260s enrolled 328 HIV-infected antiretroviral treatment (ART) naïve participants without known CVD or diabetes mellitus. All participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine plus atazanavir/ritonavir (ATV/r), darunavir/r (DRV/r), or raltegravir (RAL) as part of a large prospective clinical trial (A5257). The present analyses include 234 virologically suppressed subjects who achieved plasma HIV-1 RNA <50 copies/ml by week 24 and maintained through 3 years. Carotid intima media thickness (CIMT) was evaluated at study entry and then annually. Oxidized low-density lipoprotein (LDLox) was determined by ELISA and oxidized high-density lipoprotein (HDLox) by a novel biochemical assay. Ox-lipid fold changes from baseline were examined after 24 and 96 weeks (ratios of 1.0 indicate no change); pairwise treatment group comparisons used Wilcoxon rank-sum tests with p-values adjusted for false discovery rate control. Association analyses of ox-lipids with rate of CIMT progression over 3 years used mixed effects linear regression with ox-lipids categorized by quartiles. Participant characteristics of this virologically suppressed cohort were similar to the full substudy population. The cohort was 90%men, 48%white, 29% black, 19% Hispanic; median age was 36 years. At baseline, 12% had a 10 year risk of hard coronary heart disease >6%;13% had metabolic syndrome; prevalence of carotid lesions was low (9%). Median CD4+ cell count and HIV-1 RNA was 338 cells/mm3 and 4.6 log10 copies/ml, respectively. Over 96 weeks, HDLox declined with ATV/r and DRV/r; LDLox increased in all groups. Treatment group differences were apparent only with HDLox at week 24 between RAL and ATV/r, and RAL and DRV/r (p<0.025). Associations between the CIMT rate of progression and baseline and on-treatment ox-lipids were not apparent (p>0.40, Table). These results remained consistent upon further adjustment for lipoprotein concentration. Conclusions: Contrary to prior limited data that oxidized lipoproteins are associated with subclinical atherosclerosis, we did not find evidence of an association between early on-treatment levels of HDLox or LDLox and the rate of IMT progression estimated over 3 years on ART. Larger studies involving other CVD endpoints are needed to further study the role of ox-lipids in HIV-associated CVD.

Poster Abstracts

673 Statin Effects on oxLDL in Relationship to Plaque and Arterial Inflammation in HIV Eric Nou ; Michael Lu; Sara E. Looby; Kathleen Fitch; Elli Kim; Hang Lee; Udo Hoffmann; Steven Grinspoon; Janet Lo Massachusetts General Hosp, Boston, MA, USA

Background: Circulating oxidized LDL (oxLDL) levels are elevated in HIV-infected patients and have been associated with subclinical atherosclerosis. Statins reduce plaque on coronary computed tomography angiography (cCTA) in HIV-infected individuals but whether this effect is related to changes in oxLDL is unknown. Thus, we investigated the impact of statins on serum oxLDL and the relationship between changes in oxLDL and coronary atherosclerosis on cCTA.

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