TY - JOUR
T1 - Effect of Statin Use on Inflammation and Immune Activation Biomarkers in HIV-Infected Persons on Effective Antiretroviral Therapy
AU - Hussain, Shehnaz K.
AU - Golozar, Asieh
AU - Widney, Daniel P.
AU - Rappocciolo, Giovanna
AU - Penugonda, Sudhir
AU - Bream, Jay H.
AU - Martínez-Maza, Otoniel
AU - Jacobson, Lisa P.
N1 - Funding Information:
The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Data Analysis and Coordination Center (Gypsyamber D’Souza, Stephen Gange and Elizabeth Golub), U01-HL146193; Chicago-Northwestern CRS (Steven Wolinsky), U01-HL146240; Los Angeles CRS (Roger Detels), U01-HL146333; Pittsburgh CRS ( Jeremy Martinson and Charles Rinaldo), U01-HL146208. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional cofunding from the Eu-nice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). MWCCS data collection is also supported by UL1-TR000004 (UCSF CTSA), P30-AI-050409 (Atlanta CFAR), P30-AI-050410 (UNC CFAR), and P30-AI-027767 (UAB CFAR). Additional support for this work was obtained from the UCLA AIDS Institute, the UCLA Center for AIDS Research (CFAR; AI28697), and the UCLA Jonsson Comprehensive Cancer Center ( JCCC; CA016042) and from R01-CA168482 to R21-CA200420.
Funding Information:
Additional support for this work was obtained from the UCLA AIDS Institute, the UCLA Center for AIDS Research (CFAR; AI28697), and the UCLA Jonsson Comprehensive Cancer Center ( JCCC; CA016042) and from R01- CA168482 to R21-CA200420.
Publisher Copyright:
© 2021 Mary Ann Liebert Inc.
PY - 2021/5
Y1 - 2021/5
N2 - Immune activation and inflammation are hallmarks of chronic HIV infection and are etiologically linked to major causes of morbidity and mortality among HIV-infected persons, including coronary artery disease and cancer. Systemic immune activation is dampened, but not resolved, with use of combination antiretroviral therapy (cART). Statins are cardioprotective drugs that also appear to have immunomodulatory and anti-inflammatory properties. We sought to understand the association between statin use, cART, and levels of circulating immune markers in a longitudinal cohort study. From 2004 to 2009, statin use was ascertained in male participants of the Multicenter AIDS Cohort Study (MACS) using interviewer-administered questionnaires. Twenty-four circulating markers of immune activation and inflammation were measured in archived serial samples from a subset of cohort members using multiplex assays. Propensity-adjusted generalized gamma models were used to compare biomarkers' distributions by statin use, and multivariable linear regression models were used to assess the effect of initiating statin on these biomarkers. Overall, 1,031 cART-exposed individuals with HIV infection were included in this study. Statin use was reported by 31.5% of cART-exposed participants. Compared to nonstatin users on cART, statin users on cART had lower levels of IP-10, IL-10, and IL-12p70, and the effect of statin use was decreased in participants using lipophilic statins (atorvastatin, simvastatin, fluvastatin, or lovastatin); these results were statistically significant (p < .05). Among cART users not on aspirin, starting statins decreased levels of high sensitivity c-reactive protein (hsCRP), IL-12p70, and IL-6. Statin therapy is associated with reduced levels of certain biomarkers of immune activation and inflammation in cART users, which may contribute to a lower burden of disease.
AB - Immune activation and inflammation are hallmarks of chronic HIV infection and are etiologically linked to major causes of morbidity and mortality among HIV-infected persons, including coronary artery disease and cancer. Systemic immune activation is dampened, but not resolved, with use of combination antiretroviral therapy (cART). Statins are cardioprotective drugs that also appear to have immunomodulatory and anti-inflammatory properties. We sought to understand the association between statin use, cART, and levels of circulating immune markers in a longitudinal cohort study. From 2004 to 2009, statin use was ascertained in male participants of the Multicenter AIDS Cohort Study (MACS) using interviewer-administered questionnaires. Twenty-four circulating markers of immune activation and inflammation were measured in archived serial samples from a subset of cohort members using multiplex assays. Propensity-adjusted generalized gamma models were used to compare biomarkers' distributions by statin use, and multivariable linear regression models were used to assess the effect of initiating statin on these biomarkers. Overall, 1,031 cART-exposed individuals with HIV infection were included in this study. Statin use was reported by 31.5% of cART-exposed participants. Compared to nonstatin users on cART, statin users on cART had lower levels of IP-10, IL-10, and IL-12p70, and the effect of statin use was decreased in participants using lipophilic statins (atorvastatin, simvastatin, fluvastatin, or lovastatin); these results were statistically significant (p < .05). Among cART users not on aspirin, starting statins decreased levels of high sensitivity c-reactive protein (hsCRP), IL-12p70, and IL-6. Statin therapy is associated with reduced levels of certain biomarkers of immune activation and inflammation in cART users, which may contribute to a lower burden of disease.
KW - HIV
KW - cytokine
KW - immune activation
KW - inflammation
KW - statins
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U2 - 10.1089/aid.2020.0127
DO - 10.1089/aid.2020.0127
M3 - Article
C2 - 33238713
AN - SCOPUS:85105744633
SN - 0889-2229
VL - 37
SP - 357
EP - 367
JO - AIDS research and human retroviruses
JF - AIDS research and human retroviruses
IS - 5
ER -