CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

616 EXERCISE, OXIDATIVE STRESS, AND FIBRINOLYTIC FUNCTION IN HIV-1 INFECTED ADULTS Elizabeth Connick 1 , Jared Greiner 2 , Caitlin Dow 2 , Kyle Diehl 2 , Brian Stauffer 3 , Christopher DeSouza 2 1 Univ of Arizona, Tucson, AZ, USA, 2 Univ of Colorado Boulder, Boulder, CO, USA, 3 Univ of Colorado Denver, Aurora, CO, USA

Background: The capacity of the endothelium to release tissue-type plasminogen activator (t-PA), the primary activator of the fibrinolytic system, is the primary endogenous defense mechanism against intravascular fibrin deposition and thrombosis. We have previously demonstrated that the ability of the endothelium to release t-PA is markedly blunted in HIV-1-infected adults. Moreover, this dysfunction is due, in large part, to oxidative stress. Regular aerobic exercise is an effective lifestyle intervention for improving cardiovascular health and reducing cardiovascular risk. We tested the hypothesis that: 1) regular aerobic exercise improves endothelial fibrinolytic capacity in HIV-1-seropositive adults; and 2) increased endothelial capacity to release t-PA is mediated by a reduction in oxidative stress. Methods: Net endothelial release of t-PA was determined, in vivo, in response to intra-brachial infusions of bradykinin (BK: 125-500 ng/min) and sodium nitroprusside (SNP: 2.0-8.0 mcg/min). BK was selected to stimulate endothelial t-PA release due to its effectiveness at eliciting and local and rapid response. SNP was required to establish that any observed differences in t-PA release to BK were not due to increased blood flow related sheer stress. To determine the effects of oxidative stress on endothelial t-PA release, the BK and SNP dose response curves were repeated with a co-infusion of the antioxidant vitamin C (24 mg/min). 17 HIV-1-seropositive adults (age: 37±2 yr; 12M/5F) on stable antiretroviral therapy completed the home-based exercise intervention (walking ~4.9 d/wk, ~50 min/d @~71% of maximal heart rate). Results: The capacity of the endothelium to release t-PA in response to BK was significantly higher after (from -1.4±0.9 to 89.4±11.6 ng/100 mL tissue/min) vs before (-1.4±0.7 to 48.1±6.5 ng/100 mL tissue/min) exercise training. Importantly, before exercise training the co-infusion of vitamin C significantly increased endothelial t-PA release in response to BK (-2.2±1.3 to 95.5±10.1 ng/100 mL tissue/min). However, after exercise training the co-infusion of vitamin C did not significantly increase endothelial t-PA release (-1.1±0.9 to 101.6±15.3 ng/100 mL tissue/min). There was no effect of exercise training on t-PA release to SNP. Conclusion: In summary, habitual aerobic exercise improves endothelial fibrinolytic function in HIV-1-seropositive adults. This adaptation appears to be mediated by a reduction in oxidative stress. 617 VITAMIN D DEFICIENCY IMPAIRS THE BENEFICIAL EFFECTS OF STATIN IN TREATED HIV Corrilynn O. Hileman 1 , Vin Tangpricha 2 , Abdus Sattar 1 , Grace A. McComsey 1 1 Case Western Reserve Univ, Cleveland, OH, USA, 2 Emory Univ, Atlanta, GA, USA Background: Vitamin D deficiency is common in HIV. Statins may increase vitamin D levels and it is unknown whether vitamin D status modifies the effect of statins on cardiovascular disease. Methods: The SATURN-HIV study is a 96-week, randomized, placebo-controlled clinical trial designed to evaluate the effect of rosuvastatin 10 mg daily on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy with fasting LDL ≤130 mg/dL and heightened immune activation (proportion of CD8+ T-cells that express CD38 and HLA-DR ≥19%) and/or inflammation (high sensitivity C-reactive protein ≥2 mg/L). In this secondary analysis, mixed effects linear modeling and ANOVA were used to assess the rosuvastatin effect on plasma 25-hydroxyvitamin D [25(OH)D] levels over time and to determine whether baseline vitamin D status modifies the effect of rosuvastatin on changes in markers of subclinical vascular disease, immune activation, inflammation, lipids and insulin resistance that differed between groups over the study. See Figure for specific outcomes tested. Results: 147 adults were randomized (72 to rosuvastatin, 75 to placebo). Seventy-eight percent were men and 68%were African American. Mean age was 45 years. Mean current and nadir CD4+ T-cell counts were 640 and 200 cells/mm3, respectively, and known duration of HIV infection was 12 years. All participants were on ART by design (51% on protease inhibitor- and 49% on efavirenz-containing regimens) and 76% had HIV-1 RNA level <48 (range 20-600) copies/ml. Baseline 25(OH)D levels were similar (overall mean 18 ng/ml) with 65% of participants below 20 ng/ml. Changes in 25(OH)D at 96 weeks were small and not significant within- or between-groups. There were significant group by vitamin D status interactions for changes in LDL, proportion of CD14dimCD16+TF+monocytes, lipoprotein-associated phospholipase A2 and common carotid artery intima media thickness at most time points including week 96. For each of these outcomes, the beneficial effects of rosuvastatin were either not apparent or attenuated in participants with vitamin D deficiency (25(OH)D levels <20 ng/ml) (see Figure). Conclusion: While levels of 25(OH)D did not change with rosuvastatin, baseline vitamin D deficiency decreased the effectiveness of rosuvastatin. Vitamin D supplementation may be warranted for deficient patients initiating statin therapy.

Poster and Themed Discussion Abstracts

CROI 2017 262