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Randomized Controlled Trial
. 2016 Jan 2;30(1):65-73.
doi: 10.1097/QAD.0000000000000885.

Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV

Corrilynn O Hileman  1 , Randi Turner, Nicholas T Funderburg, Richard D Semba, Grace A McComsey
Affiliations
Randomized Controlled Trial

Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV

Corrilynn O Hileman et al. AIDS. .

Abstract

Background: Oxidative stress plays a significant role in atherosclerosis development. HIV infection has been linked with heightened cardiovascular disease risk. HMG-CoA reductase inhibitors may reduce oxidative stress and subsequently subclinical vascular disease in HIV.

Design/methods: This is a randomized, placebo-controlled trial to evaluate the effect of rosuvastatin in HIV-infected adults on stable antiretroviral therapy with low-density lipoprotein less than 130 mg/dl and increased inflammation or T-cell activation on subclinical vascular disease. Changes over 48 weeks in oxidative stress markers, oxidized low-density lipoprotein (oxLDL) and F2-isoprostane/creatinine ratio (F2-IsoP/Cr), were compared between groups. Spearman correlation and multivariable linear regression were used to evaluate relationships between changes in markers of oxidative stress, inflammation and monocyte activation and carotid intima media thickness (CIMT).

Results: One hundred and forty-seven adults enrolled (72 to rosuvastatin and 75 to placebo). In the rosuvastatin group, oxLDL decreased significantly over 24 weeks compared to placebo [mean absolute change in log-oxLDL for rosuvastatin -0.2 ± 0.468 log U/l (P < 0.001 within-group) vs. placebo -0.018 ± 0.456 log U/l (P = 0.83 within-group); P = 0.004 between groups] and this change was linked with changes in soluble CD14 and proportion of patrolling monocytes (CD14dimCD16). Although oxLDL levels increased after initially declining and were not different from placebo at week 48, the early improvement in oxLDL was associated with improved CIMT at week 48. Changes in F2-IsoP/Cr were not significant between groups.

Conclusion: Rosuvastatin decreases oxLDL levels early after initiation and is associated with decreased monocyte activation. Early improvement in oxLDL is linked with improved CIMT in treated HIV infection.

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Conflict of interest statement

Conflicts of interest

G.A.M. has received research grants from BMS, Gilead Sciences and GSK, has served as a consultant to BMS, GSK, Janssen, Merck and Gilead, as a speaker for BMS, GSK and Tibotec and on the DSMB for a Pfizer-sponsored trial. N.T.F. has served as a consultant for Gilead Sciences. All other authors report no conflicts.

Figures

Fig. 1
Fig. 1. Change in oxidized low density lipoprotein at each time point by randomization group
(a) Mean log-transformed oxidized low density lipoprotein levels at each time point are shown. P-values are for between-group tests. (b) Mean absolute change in log transformed oxidized low density lipoprotein levels with standard deviation are shown. P-values are for between-group tests. *Denotes significant (P < 0.05) within-group change.
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