CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

PWV (log -0.13m/s, p=0.005) but no adjusted change in PWV over time (log +0.23m/s, p=0.13). Conclusion: In PLWH from low income settings with high pre-ART T cell activation, PWV improves (declines) on ART. However, we identified a cluster with a hyper-inflamed biological profile in whom PWV increased, with IL1RA a potential marker of this hyper-inflamed state and vascular dysunction. The clinical implications of this phenotype require further research.

1 VA North Texas Health Care Center, Dallas, TX, USA, 2 University of Texas Southwestern, Dallas, TX, USA, 3 Prism Health North Texas, Dallas, TX, USA, 4 University of California San Diego, San Diego, CA, USA, 5 University of Alabama at Birmingham, Birmingham, AL, USA, 6 University of Pennsylvania, Philadelphia, PA, USA Background: The mechanism(s) beyond traditional risk factors driving the increased atherosclerotic cardiovascular disease (ASCVD) risk among people with HIV (PWH) are unclear. In the general population, incident ASCVD events are associated with impaired macrophage HDL cholesterol efflux capacity (CEC), a derangement previously reported among PWH. We hypothesized that impaired CEC is associated with incident ASCVD events among PWH receiving ART. Additionally, we evaluated whether impaired CEC contributes to the differential ASCVD event rates reported for certain ARVs. Methods: We selected participants from the AIDS Clinical Trials Group (ACTG) Longitudinally Linked Randomized Trials (ALLRT) cohort with samples available after 48 weeks of ART who experienced an ASCVD event (acute myocardial infarction or stroke) and matched them 5:1 in a case-cohort study design with participants who remained free of ASCVD. We measured macrophage- specific CEC to apolipoprotein B-depleted plasma from cases and controls at week 48 following ART initiation and evaluated the association of CEC with incident ASCVD event, controlling for ASCVD risk factors Finally, we compared CEC in participants randomized to ATV vs. Darunavir (DRV), Efavirenz (EFV) or Raltegravir (RAL), and to ABC vs. Tenofovir (TDF). Results: We included 1024 participants (114 cases and 910 randomly selected controls); Mean age 41 y, 80%Male, 47% Black, 29% current smokers, mean SBP 121, mean total cholesterol 191, mean BMI 27, viral suppression was 90% at week 48. In a fully adjusted model that included traditional risk factors, HDL cholesterol , and virologic suppression status at week 48, hazard ratio for ASCVD per 1 SD increase in CEC was 0.86 (95% CI: 0.70 – 1.06). CEC was not higher in participants who had achieved virologic suppression (VL<50 copies/mL; n=817): p=0.19. ATV was associated with a higher CEC when compared to other “third” drugs (DRV, EFV or RAL). There was a trend toward lower CEC with ABC compared to TDF. Table 1 summarizes the models. Conclusion: Unlike data from the general population, we did not observe an inverse association of CEC with risk of ASCVD among HIV-infected participants on ART. ATV use was associated with less impaired CEC than DRV, EFV and RAL, but not with lower risk of incident ASCVD events. There was a trend for lower CEC with ABC vs. TDF exposure. Larger studies will be required to fully evaluate whether certain ARVs alter CEC and its role in ASCVD progression.

647 TOCILIZUMAB ALTERS LIPIDS IN HIV+ INDIVIDUALS IN A RANDOMIZED, DOUBLE-BLIND STUDY Emily Bowman 1 , Morgan Cichon 1 , Kenneth Riedl 1 , Jane Baum 2 , Michael L. Freeman 2 , Michael M. Lederman 2 , Benigno Rodriguez 2 , Nicholas Funderburg 1 1 The Ohio State University, Columbus, OH, USA, 2 Case Western Reserve University, Cleveland, OH, USA Background: Cardiovascular disease (CVD) risk is increased in HIV infection, despite suppressive antiretroviral therapy (ART). Increased IL-6 levels are linked to CVD, and are predictive of morbidity and mortality in HIV infection. Tocilizumab (TCZ), a monoclonal antibody that inhibits IL-6 activity, can reduce inflammation and improve disease outcomes in individuals with rheumatoid arthritis (RA). Increased serum lipids (total cholesterol, HDL, LDL) were observed following TCZ treatment, but were not significantly linked to CVD risk in the RA population. The effects of TCZ on inflammation, lipid profiles, and clinical outcomes in HIV+ individuals is not known. Methods: This was a phase I/II double-blind, placebo controlled, crossover trial of TCZ administered intravenously (IV) every 4 weeks for 3 doses. Male and female ART-treated HIV+ study participants were randomized to receive either TCZ or placebo followed by a 12 week washout period and treatment crossover. At each study visit, lipid panels and detailed lipidomics analyses, measuring ~1200 lipid species across 13 classes, were performed by mass spectrometry. Results: Traditional lipid measurements for total cholesterol, LDL, and VLDL levels were increased following TCZ treatment (p<0.01 for all). Plasma concentrations of total lipids (p=0.0001), and concentrations of the lipid classes, CE, CER, DAG, FFA, HCER, LPC, LPE, PC, PE, SM, TAG, were increased following TCZ treatment compared to baseline and placebo (p<0.05 for all). We also measured significant changes in concentrations of 129 individual lipid species (p<0.05). Additionally, fatty acid composition was altered among lipid species; TCZ treatment reduced the proportion of free saturated fatty acids (SaFAs) (47% vs 43%, p=0.05), and increased the proportion of free monounsaturated fatty acids (MUFAs) (32% vs. 35%, p=0.06) and polyunsaturated fatty acids (PUFAs) (21% vs 22%). In vitro exposure of PBMCs to SaFAs induced inflammatory cytokine production and monocyte activation. Conclusion: TCZ therapy alters lipid profiles in HIV+ individuals on ART. The concentrations of multiple lipid classes increased during TCZ treatment, however, the SaFA/UFA ratio was improved for some classes. IL-6 blockade may reduce some indices of inflammation in HIV+ individuals, but also exacerbates lipid levels, potentially limiting benefits in this population. Further study is needed to determine the consequences of TCZ-mediated lipidome alterations on CVD risk. 648 HDL CHOLESTEROL EFFLUX CAPACITY AND INCIDENT ASCVD IN HIV: IMPACT OF HAART Roger Bedimo 1 , Colby Ayers 2 , Jason Gillman 3 , Amneris Luque 2 , Ayea El- Ghazali 2 , Constance A. Benson 4 , Edgar T. Overton 5 , Pablo Tebas 6 , Anand Rohatgi 2

Poster Abstracts

649 EVIDENCE FOR PLEIOTROPIC EFFECTS OF LIPID-LOWERING DRUGS DURING SUPPRESSIVE HAART Henning J. Drechsler 1 , Colby Ayers 2 , James Cutrell 1 , Pablo Tebas 3 , Roger Bedimo 1 , for the University of Texas Southwestern School of Medicine 1 VA North Texas Health Care Center, Dallas, TX, USA, 2 University of Texas Southwestern, Dallas, TX, USA, 3 University of Pennsylvania, Philadelphia, PA, USA Background: Statin use in HIV-infected patients is associated with improved virologic control, with decreased all-cause mortality, and decreased rates of non-AIDS defining conditions (NADC) like cancer and liver fibrosis. This has

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