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Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection.

ABSTRACT: To determine the effect of statins on the progression of subclinical atherosclerosis in a population of HIV-infected adults on antiretroviral therapy.Double-blind, randomized clinical trial.Stopping Atherosclerosis and Treating Unhealthy Bone with RosuvastatiN in HIV infection was a 96-week double-blind, randomized clinical trial of 10?mg daily rosuvastatin (n?=?72) vs. placebo (n?=?75) in a population of HIV-infected subjects on stable antiretroviral therapy with LDL-cholesterol 130?mg/dl or less (?3.36?mmol/l) and evidence of heightened T-cell activation (CD8CD38HLA-DR ?19%) or increased inflammation [high sensitivity C-reactive protein ?2?mg/l (?19?mmol/l)]. Change in common carotid artery intima-media thickness (IMT) (CCA-IMT) was the primary outcome. Secondary outcomes were changes in LDL and coronary artery calcium.Median (Q1, Q3) age was 46 (40, 53) years; 78% were man and 68% African-American; 49% were on a protease inhibitor. Mean (95% confidence interval) change in LDL was -21 (-27 to -15)?mg/dl [-0.54 (-0.70 to -0.39)?mmol/l] in the rosuvastatin arm. In a multivariable linear mixed-effects model, assignment to statin was associated with 0.019?mm (95% confidence interval: 0.002-0.037?mm) less progression of CCA-IMT over 96 weeks. We did not find substantial effect modification by level of inflammation or immune activation biomarkers, except for a borderline statistically significant interaction for soluble vascular cell adhesion molecule (P?=?0.065). There was no difference in coronary artery calcium change (P?=?0.61).Rosuvastatin effectively lowers LDL and appears to substantially slow progression of CCA-IMT in patients with treated HIV infection. Future study is needed to determine whether subjects with higher levels of inflammation or immune activation derive greater cardiovascular benefit from statin therapy.

SUBMITTER: Longenecker CT

PROVIDER: S-EPMC5007142 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection.

Longenecker Chris T CT Sattar Abdus A Gilkeson Robert R McComsey Grace A GA

AIDS (London, England) 20160901 14

<h4>Objective</h4>To determine the effect of statins on the progression of subclinical atherosclerosis in a population of HIV-infected adults on antiretroviral therapy.<h4>Design</h4>Double-blind, randomized clinical trial.<h4>Methods</h4>Stopping Atherosclerosis and Treating Unhealthy Bone with RosuvastatiN in HIV infection was a 96-week double-blind, randomized clinical trial of 10 mg daily rosuvastatin (n = 72) vs. placebo (n = 75) in a population of HIV-infected subjects on stable antiretrov ...[more]

PMID: 27203715

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Project description:BackgroundSoluble Tumor Necrosis Factor Weak Inducer of Apoptosis (sTWEAK) has been proposed as a novel biomarker of cardiovascular disease risk. This study compares levels of sTWEAK, sCD163 and the sCD163/sTWEAK ratio in HIV-infected and uninfected patients and their associations with cardiovascular and inflammatory factors.MethodsThe data for our analysis come from 274 HIV-infected adults and 59 controls. HIV participants were on stable antiretroviral therapy (ART). Wilcoxon-Mann-Whitney tests were used for comparing markers between HIV-infected participants with HIV viral load <50 copies/mL (aviremic group), HIV-infected participants with detectable viremia (HIV-1 RNA ≥50 copies/mL; viremic group) and HIV negative participants. Multivariable quantile regression analyses were used to assess associations of sTWEAK and sCD163 with other markers of inflammation and carotid intima-media thickness (cIMT).ResultsOverall, 74% of participants were male; 59% were African-Americans; median age was 40 years and CD4 595 cells/mm3. Overall, HIV-infected participants had reduced sTWEAK and increased sCD163 levels compared to HIV-uninfected participants (p = 0.0001 for both markers). In addition, these biomarkers were significantly different between HIV-infected viremic and aviremic patients (p ≤ 0.01 for both markers). In multivariable models, sTWEAK and sCD163 in aviremic patients were significantly correlated with common carotid artery IMT (p ≤ 0.05). In HIV-infected aviremic participants, sTWEAK and sCD163 were both associated with IL-6, CD14 + CD16 + monocytes (p ≤ 0.02); additionally, sCD163 was associated with D-dimer- (β = -69.5, 0.05), VCAM (β = 72.4, p = 0.05), TNF RI (β = 91.1, p < 0.01), and TNF RII (β = 87.8, p < 0.01).ConclusionsHIV-infected participants showed increased systemic inflammatory and monocyte activation markers. Soluble CD163 and sTWEAK levels were associated with carotid intima-media thickness.

Project description:ObjectiveTo evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.DesignProspective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.MethodsTwenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.ResultsAmong 24 acylcarnitine species, C8-carnitines and C20 : 4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P < 0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P < 0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs) = 1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR = 1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR = 1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR = 1.03 (0.76-1.40)] or HIV-negative individuals [RR = 1.02 (0.69-1.52)].ConclusionIn two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.

Project description:ImportancePersons living with HIV (PLWH) have increased risk for cardiovascular disease, and inflammation is thought to contribute to this excess risk. Production of HIV during otherwise effective antiretroviral therapy (ART) has been associated with inflammation.ObjectiveTo determine whether higher levels of viral persistence are associated with atherosclerosis as assessed by changes in carotid artery intima-media thickness (IMT) over time.Design, setting, and participantsIn this cohort study, intima-media thickness, a validated marker of atherosclerosis, was assessed over time in a cohort of treated PLWH with viral suppression. Cell-associated HIV DNA and RNA and change in IMT, adjusted for demographics, cardiovascular risk factors, and HIV-related factors, were examined, as well as which factors were associated with viral persistence. One hundred fifty-two PLWH with undetectable viral loads for at least 6 months before study enrollment were recruited from HIV clinics affiliated with 2 hospitals in San Francisco, California, from January 1, 2003, to December 31, 2012. Data were analyzed from February 7, 2018, to May 12, 2020.ExposuresCell-associated HIV RNA and DNA were measured using enriched CD4+ T cells from cryopreserved peripheral blood mononuclear cells.Main outcomes and measuresCarotid IMT was measured at baseline and the last visit, with a mean (SD) follow-up of 4.2 (2.7) years, using high-resolution B mode ultrasonography. The main study outcomes were baseline IMT, annual IMT progression, and incident plaque, defined as a focal region of carotid IMT of greater than 1.5 mm.ResultsThe analysis included 152 PLWH (140 [92.1%] male; median age, 48.5 [interquartile range {IQR}, 43.3-53.7] years). Older age, smoking, medications for hypertension, higher low-density lipoprotein levels, and higher interleukin 6 levels were associated with higher baseline mean IMT, whereas cell-associated HIV DNA (estimate, -0.07% [95% CI, -6.1% to 6.4%]; P = .98), and HIV RNA levels (estimate, -0.8% [95% CI, -5.9% to 4.4%]; P = .75) were not. Levels of HIV RNA (0.017 [95% CI, 0.000-0.034] mm/y; P = .047) and HIV DNA (0.022 [95% CI, 0.001-0.044] mm/y; P = .042) were significantly associated with annual carotid artery IMT progression in unadjusted models only. Both HIV RNA (incidence risk ratio [IRR], 3.05 [95% CI, 1.49-6.27] per IQR; P = .002) and HIV DNA (IRR, 3.15 [95% CI, 1.51-6.57] per IQR; P = .002) were significantly associated with incident plaque, which remained significant after adjusting for demographics, cardiovascular risk factors, and HIV-related factors (IRR for HIV RNA, 4.05 [95% CI, 1.44-11.36] per IQR [P = .008]; IRR for HIV DNA, 3.35 [95% CI, 1.22-9.19] per IQR [P = .02]). Higher C-reactive protein levels were associated with higher cell-associated HIV RNA (estimate, 20.7% [95% CI, 0.9%-44.4%] per doubling; P = .04), whereas higher soluble CD14 levels were associated with HIV DNA (estimate, 18.6% [95% CI, 3.5%-35.8%] per 10% increase; P = .01). Higher soluble CD163 levels were associated with a higher HIV RNA:DNA ratio (difference, 63.8% [95% CI, 3.5%-159.4%]; P = .04).Conclusions and relevanceThese findings suggest that measurements of viral persistence in treated HIV disease are independently associated with incident carotid plaque development. The size and transcriptional activity of the HIV reservoir may be important contributors to HIV-associated atherosclerosis.

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Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection.

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Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection.

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