Effect of Statin Therapy in Reducing the Risk of Serious Non-AIDS-Defining Events and Nonaccidental Death

被引:53
作者
Overton, E. T. [1 ]
Kitch, D. [2 ]
Benson, C. A. [3 ]
Hunt, P. W. [4 ]
Stein, J. H. [5 ]
Smurzynski, M. [2 ]
Ribaudo, H. J. [2 ]
Tebas, P. [6 ]
机构
[1] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA
[2] Harvard Univ, Sch Publ Hlth, Dept Biostat, Ctr Biostat AIDS Res, Boston, MA 02115 USA
[3] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA
[4] Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA 94143 USA
[5] Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA
[6] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA
关键词
HIV infection; statins; ALLRT; inflammation; immune activation; MARGINAL STRUCTURAL MODELS; IMMUNE ACTIVATION; HIV-INFECTION; T-CELLS; ANTIRETROVIRAL THERAPY; CAUSAL INFERENCE; DOUBLE-BLIND; DISEASE; INFLAMMATION; MORTALITY;
D O I
10.1093/cid/cit053
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Excessive inflammation persists despite antiretroviral treatment. Statins decrease cardiovascular (CV) disease risk by reducing low-density lipoprotein cholesterol and inflammation. We performed an exploratory analysis to evaluate whether statin therapy decreased risk of non-AIDS-defining events and nonaccidental death. Methods. A total of 3601 subjects not on a statin from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort were included. Outcome was time to first clinical event (CV event, renal or hepatic disease, incident diabetes, thrombotic/embolic event, nontraumatic fracture, non-AIDS-defining malignancy, serious bacterial infection, or nonaccidental death); event categories were also analyzed separately. Inverse probability of treatment and censoring weighted Cox proportional hazard models were used to assess the causal statin effect. Differential statin effects by baseline covariates were evaluated. Results. Over 15 135 person-years (PY) of follow-up, 484 subjects initiated statins; 616 experienced an event (crude event rate, 4.4/100 PY on a statin and 4.1/100 PY not on a statin); the unadjusted hazard ratio (HR) was 1.17 (95% confidence interval [CI], .91-1.50). In a final weighted model, the adjusted HR (AHR) was 0.81 (95% CI, .53-1.24). Results for other clinical events were similar, except for malignancies (AHR, 0.43 [95% CI, .19-. 94]) and bacterial infections (AHR, 1.30 [95% CI, .64-2.65]). No differential statin effects by baseline covariates were detected. Conclusions. Although statin therapy was not associated with a reduction in time to all non-AIDS-defining event or nonaccidental death, it was associated with a statistically significant 57% reduction in non-AIDS-defining malignancies. Confirmatory studies are needed to evaluate statin-associated reduction in risk of cancer and non-AIDS-associated morbidities.
引用
收藏
页码:1471 / 1479
页数:9
相关论文
共 40 条
[1]   Immunosenescence: emerging challenges for an ageing population [J].
Aw, Danielle ;
Silva, Alberto B. ;
Palmer, Donald B. .
IMMUNOLOGY, 2007, 120 (04) :435-446
[2]   Bone turnover, osteoprotegerin/RANKL and inflammation with antiretroviral initiation: tenofovir versus non-tenofovir regimens [J].
Brown, Todd T. ;
Ross, Allison C. ;
Storer, Norma ;
Labbato, Danielle ;
McComsey, Grace A. .
ANTIVIRAL THERAPY, 2011, 16 (07) :1063-1072
[3]   Association Between Systemic Inflammation and Incident Diabetes in HIV-Infected Patients After Initiation of Antiretroviral Therapy [J].
Brown, Todd T. ;
Tassiopoulos, Katherine ;
Bosch, Ronald J. ;
Shikuma, Cecilia ;
McComsey, Grace A. .
DIABETES CARE, 2010, 33 (10) :2244-2249
[4]   Premature Aging of T cells Is Associated With Faster HIV-1 Disease Progression [J].
Cao, Weiwei ;
Jamieson, Beth D. ;
Hultin, Lance E. ;
Hultin, Patricia M. ;
Effros, Rita B. ;
Detels, Roger .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2009, 50 (02) :137-147
[5]   HMG-CoA reductase inhibitors (statins) use and risk of non-Hodgkin lymphoma in HIV-positive persons [J].
Chao, Chun ;
Xu, Lanfang ;
Abrams, Donald I. ;
Towner, William J. ;
Horberg, Michael A. ;
Leyden, Wendy A. ;
Silverberg, Michael J. .
AIDS, 2011, 25 (14) :1771-1777
[6]   Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly [J].
Cohen, HJ ;
Harris, T ;
Pieper, CF .
AMERICAN JOURNAL OF MEDICINE, 2003, 114 (03) :180-187
[7]   Impact of Antiretroviral Therapy on Tuberculosis Incidence Among HIV-Positive Patients in High-Income Countries [J].
del Amo, Julia ;
Moreno, Santiago ;
Bucher, Heiner C. ;
Furrer, Hansjakob ;
Logan, Roger ;
Sterne, Jonathan ;
Perez-Hoyos, Santiago ;
Jarrin, Inma ;
Phillips, Andrew ;
Lodi, Sara ;
van Sighem, Ard ;
de Wolf, Frank ;
Sabin, Caroline ;
Bansi, Loveleen ;
Justice, Amy ;
Goulet, Joseph ;
Miro, Jose M. ;
Ferrer, Elena ;
Meyer, Laurence ;
Seng, Remonie ;
Toulomi, Giota ;
Gargalianos, Panagiotis ;
Costagliola, Dominique ;
Abgrall, Sophie ;
Hernan, Miguel A. .
CLINICAL INFECTIOUS DISEASES, 2012, 54 (09) :1364-1372
[8]   Linking lipids to Alzheimer's disease: cholesterol and beyond [J].
Di Paolo, Gilbert ;
Kim, Tae-Wan .
NATURE REVIEWS NEUROSCIENCE, 2011, 12 (05) :284-296
[9]   Workshop on HIV infection and aging: What is known and future research directions [J].
Effros, Rita B. ;
Fletcher, Courtney V. ;
Gebo, Kelly ;
Halter, Jeffrey B. ;
Hazzard, William R. ;
Horne, Frances McFarland ;
Huebner, Robin E. ;
Janoff, Edward N. ;
Justice, Amy C. ;
Kuritzkes, Daniel ;
Nayfield, Susan G. ;
Plaeger, Susan F. ;
Schmader, Kenneth E. ;
Ashworth, John R. ;
Campanelli, Christine ;
Clayton, Charles P. ;
Rada, Beth ;
Woolard, Nancy F. ;
High, Kevin P. .
CLINICAL INFECTIOUS DISEASES, 2008, 47 (04) :542-553
[10]  
El-Sadr WM, 2006, NEW ENGL J MED, V355, P2283, DOI 10.1056/NEJMoa062360