CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

618

EFFECT OF STATIN ON ARGININE METABOLITES IN TREATED HIV INFECTION Sahera Dirajlal-Fargo 1 , Vanessa El Kamari 2 , Abdus Sattar 2 , Nicholas Funderburg 3 , W. H. Wilson Tang 4 , Grace A. McComsey 2 1 Rainbow Babies and Children’s Hosp–Case Western Sch of Med, Cleveland, OH, USA, 2 Case Western Reserve Univ, Cleveland, OH, USA, 3 Ohio State Univ, Columbus, OH, USA, 4 Cleveland Clinic, Cleveland, OH, USA Background: Asymmetric dimethylarginine (ADMA), an arginine metabolite, is an endogenous inhibitor of nitric oxide and an independent risk factor of cardiovascular disease (CVD). Statins lower ADMA in HIV negative populations but it is unknown whether statins have similar effect in HIV+ populations, and whether such an effect could contribute to the favorable changes on carotid intima media thickness (cIMT). This analysis examines the relationship between statin, ADMA and cIMT. Methods: This secondary analysis of SATURN-HIV trial, in which HIV+ adults on stable antiretroviral therapy (ART), with HIV-1 RNA< 1,000 copies/mL and LDL-cholesterol <130mg/dL were randomized to 10mg daily rosuvastatin or placebo. Arginine metabolites, including ADMA and global arginine availability ratio (GABR), and markers of inflammation were assessed at baseline and at 48 weeks, cIMT was measured at baseline, 48 and 96 weeks. Classical t-tests were used for comparison between groups. Spearman correlations were used to explore relationships between variables. Linear mixed-effect model was used to assess the interaction of ADMA and statin on cIMT. Results: Overall, 79%were male, 68% African Americans, with median age of 46 years. In the statin arm, no significant change in ADMA levels was observed at 48 weeks (0.70%), whereas a significant increase (23.78%) was observed in the placebo group (Fig.1). Change in ADMA was significantly correlated with changes in intracellular cell adhesion molecule (p=0.02) and in T-cell activation markers (CD8+CD38+, p=0.05 and CD4+ CD38+ HLA-DR+, p<0.01). Moreover, a significant decrease in GABR (33.56%, p=0.03) was observed at 48 weeks in the statin arm, while no significant change was observed in the placebo arm (p=0.32). Elevated baseline ADMA (highest tertile) was independently associated with a 0.03mm increase in cIMT (p=0.03) after adjusting for statin and study duration. No interaction was seen between baseline ADMA and statin treatment on change in cIMT (p=0.20). Conclusion: Daily rosuvastatin in HIV+ subjects on ART prevented the increase overtime in ADMA levels on ART. Elevated baseline levels of ADMA were associated with increases in cIMT. However, the favorable effect of rosuvastatin on cIMT was independent of the arginine pathway. Further studies are warranted to investigate the role of the arginine metabolites in HIV and specifically whether arginine supplementation could enhance the beneficial effects of statin in this population.

Poster and Themed Discussion Abstracts

619 THE LARGE GAP BETWEEN STATIN ELIGIBILITY AND PRESCRIPTION AMONG HIV+ IN NORTH AMERICA Keri N. Althoff 1 , Micheal A. Horberg 2 , Joseph J. Eron 3 , Stephen J. Gange 1 , Heidi M. Crane 4 , Amy Justice 5 , Mari Kitahata 4 , Joseph B. Margolick 1 , Oghenowede Eyawo 6 , Richard D. Moore 1 1 The Johns Hopkins Univ, Baltimore, MD, USA, 2 Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA, 3 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 4 Univ of Washington, Seattle, WA, USA, 5 VA Connecticut Hlthcare System, West Haven, CT, USA, 6 BC Cntr for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada Background: Those aging with HIV have a higher risk of cardiovascular disease (CVD) than uninfected adults. Statins are hypothesized to impact traditional CVD risk factors, such as low-density lipoprotein (LDL) cholesterol, and may impact HIV-specific mechanisms, such as inflammation and immune activation. The objective of this study was to estimate the statin treatment gap, defined as the proportion eligible but not prescribed statins among HIV-infected adults. Methods: Data from 14 dynamic clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design were used to estimate trends in statin prescription. The statin treatment gap was defined using the final Adult Treatment Panel III guidelines as ≤1 risk factors and LDL ≥190 mg/dL, or ≥2 risk factors with 10-year predicted Framingham Risk Score (FRS) 0-20% and LDL ≥130 mg/dL, or diabetes and FRS >20% and LDL ≥130 mg/dL. The treatment gap analysis was restricted to those who had measurements needed to determine statin eligibility. Log binomial models with generalized estimating equations for repeated measures and an ordinal variable for calendar time were used to estimate the p-value for trend. Results: A total of 88,463 and 40,898 adults contributed to the estimation of the trends in statin prescription and the statin treatment gap, respectively. There were a greater proportion who were white and MSM in the gap compared with the prescription study populations (48% vs 39% p<.001 and 56% vs 49% p<.001, respectively). Over time, the proportion prescribed statins increased from 5% to 17% (p-trend<.001) (Figure 1). The statin treatment gap was large, but decreased from 70% to 58% (p-trend<.001). The gap was largest for males (72% to 59%), those with injection drug use HIV transmission risk (81% to 58%), and ever smokers (73% to 60%; all p-trend<.001). By age, the gap was largest and fluctuated among those <40 years with no clear trend (77% to 88% p-trend=.01). The decrease in the gap was similar among whites (72% to 57%) and blacks (71% to 58%), and larger in Hispanics (74% to 65%; all p-trend<.001). Conclusion: The statin treatment gap was substantial from 2003 through 2012, prior to statin guideline changes in 2013. The gap may be underestimated due to the differences in the prescription and gap populations. Given the increased risk of CVD in HIV-infected adults, further narrowing the gap between statin eligibility and prescription may preserve the health of those aging with HIV.

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