CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Methods: This randomized, double-blind, placebo-controlled trial included HIV-infected subjects on stable anti-retroviral therapy with subclinical coronary atherosclerosis and LDL-cholesterol < 130 mg/dL. Subjects were assigned to treatment with either atorvastatin or placebo for 12 months. Subjects underwent cCTA and measurements of serum oxLDL, sCD14, sCD163, lipoprotein phospholipase A 2 (Lp-PLA 2 ), and fasting lipids including direct LDL at baseline and end of the study. Multivariate regression modeling was performed to examine the effects of change in oxLDL on change in non-calcified plaque volume, controlling for baseline CD4 count, log viral load, 10-year Framingham risk, and change in direct LDL. Results: Forty HIV-infected subjects were enrolled and assigned to placebo (n=21) or atorvastatin (n=19). There was no difference in serum oxLDL at baseline between the two groups. After 12 months, serum oxLDL decreased -22.7% [95% CI -28.7 to -16.7] in the atorvastatin group and increased 7.5% [95% CI -3.3 to 18.4] in the placebo group (p < 0.0001 for comparison of change between groups). Change in oxLDL, but not direct LDL, significantly correlated with changes in non-calcified plaque volume, total plaque volume, and high risk coronary plaque features of positive remodeling and low attenuation (Table 1). The relationship between changes in oxLDL and non-calcified plaque volume was independent of the baseline 10-year Framingham risk, CD4 count, viral load, and change in direct LDL. Change in oxLDL was strongly related to change in Lp-PLA 2 (r=0.34, p=0.04) but not other immune markers in our study. Conclusions: Statins significantly reduce oxLDL levels in HIV-infected patients, and reductions in oxLDL relate strongly to improvements in coronary atherosclerosis, independent of traditional cardiovascular risk factors. Reductions in oxLDL, via effects on arterial inflammation, may be one mechanism through which statins improve atherosclerosis in HIV- infected individuals.

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The Effect of Rosuvastatin on Vascular Disease Differs by Smoking Status Corrilynn O. Hileman 1 ; ChrisT. Longenecker 2 ; Danielle Labbato 2 ; Bruce Kinley 2 ; Grace A. McComsey 2 1 MetroHlth Med Cntr, Cleveland, OH, USA; 2 Case Western Reserve Univ, Cleveland, OH, USA

Background: Smoking is an important contributor to cardiovascular disease (CVD) risk and is highly prevalent in the HIV population. We have shown that rosuvastatin improves markers of inflammation (soluble tumor necrosis factor alpha receptor-II, interferon γ inducible protein 10 and lipoprotein associated phospholipase A2), immune activation [soluble CD14, proportion of tissue factor positive patrolling (CD14dimCD16+) monocytes and proportion of activated CD4+ and CD8+ T cells (CD38+HLA-DR+)] and arrests common carotid artery intima media thickness (IMT) progression in HIV+ adults. Whether smoking status modifies these effects of rosuvastatin is unknown. Methods: The SATURN-HIV study is a randomized placebo-controlled trial to evaluate the effect of rosuvastatin (10 mg daily) on immune activation and subclinical vascular disease in HIV+ adults on stable antiretroviral therapy (ART) with LDL ≤130 mg/dL. Here we assessed whether smoking status modifies the effect of rosuvastatin on select outcome measures that differed between groups over the study. ANCOVA was used to model each outcome including a group by smoking status interaction. Stratum specific estimates are provided where the interaction was significant. Results: 147 adults were included (72 rosuvastatin; 75 placebo). Groups were similar at baseline. Overall, 78%were men, 68%were black with median age 46 years and CD4 count of 613 cell/mm 3 . 78% had HIV-1 RNA <50 cps/mL, 63%were current smokers (median packs per day 0.5) and another 16% past smokers. There was a significant group by smoking status interaction for 0-24 (p=0.01) and 0-48 (p<0.01) week changes in proportion of activated CD4+ T cells and a trend towards significance for 0-48 week change in activated CD8+ T cells (p=0.07). The interaction was also significant for 0-48 week change in CCA IMT (p<0.01) and trended towards significance for 0-96 week change in CCA IMT as well (p=0.06). The figure shows stratum specific adjusted means for these outcomes. No effect modification by smoking was detected for changes in markers of inflammation or monocyte activation. Conclusions: Current smoking modifies the effect of rosuvastatin on CCA IMT and T-cell activation, such that the beneficial effect of rosuvastatin on CCA IMT was not apparent in smokers. In HIV+ smokers, interventions such as rosuvastatin are unlikely to be as important as smoking cessation in CVD risk reduction.

Poster Abstracts

278

CROI 2016