Objective: Microbial translocation has been suggested to be a driver of immune activation and inflammation. It is hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals.
Design: Cross-sectional study of 60 HIV-infected patients on combination antiretroviral therapy with viral suppression >2 years and 31 healthy age-matched controls.
Methods: Lipopolysaccharide (LPS) was analyzed by limulus amebocyte lysate colorimetric assay. Lipids, including cholesterol, low-density lipoprotein (LDL), and triglycerides, were measured. Glucose metabolism was determined using an oral glucose tolerance test. Body composition was determined using whole-body dual-energy x-ray absorptiometry scans and magnetic resonance imaging. The Framingham risk score was used to assess risk of cardiovascular disease and myocardial infarction.
Results: HIV-infected patients had higher level of LPS compared with controls (64 pg/mL vs. 50 pg/mL, P = 0.002). Likewise, HIV-infected patients had higher triglycerides, LDL, and fasting insulin as well as evidence of lower insulin sensitivity compared with controls. Among HIV-infected patients, high LPS was associated with a higher level of triglycerides and LDL and with lower insulin sensitivity. Importantly, among HIV-infected patients, high LPS was associated with a higher Framingham risk score.
Conclusions: HIV-infected patients with suppressed viral replication had increased level of microbial translocation as measured by LPS. LPS was associated with cardiometabolic risk factors and increased Framingham risk score. Hence, the gastrointestinal mucosal barrier may be a potential therapeutic target to prevent dyslipidemia and future cardiovascular complications in HIV infection.
*Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;
†Centre of Inflammation and Metabolism, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;
‡Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway;
§Department of Radiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; and
‖Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Correspondence to: Susanne D. Nielsen, MD, DMSc, Department of Infectious Diseases, Rigshospitalet-University Hospital of Copenhagen, Blegdamsvej 9, DK 2100 Copenhagen Ø, Denmark (e-mail: firstname.lastname@example.org).
Supported by The Novo Nordisk Foundation, The Danish Council for Independent Research, Lundbeck Foundation, Lykfeldt grant, Torben and Alice Frimodts Foundation, Snedkermester Sophus Jacobsen and wife Astrid Jacobsens Foundation, Aase and Ejnar Danielsens Foundation, Agnethe Løvgreens Legat, and Janssen.
The authors have no conflicts of interest to disclose.
Presented in part with a poster “Microbial Translocation may Drive Metabolic Syndrome in HIV-Infected Individuals on Combination Antiretroviral Treatment (cART)” at AIDS XIX, Washington DC, 2012.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).
Received February 19, 2013
Accepted June 07, 2013