1 Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, VBN2 The Faculty of Medicine, Aalborg University, VBN3 Aalborg University Hospital, The Faculty of Medicine, Aalborg University, VBN4 Klinik Medicin, The Faculty of Medicine, Aalborg University, VBN5 Infektionsmedicin, The Faculty of Medicine, Aalborg University, VBN6 Centre for Health & Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.7 Research Department of Infection and Population Health, University College London, London, United Kingdom.8 Hennepin County Medical Center, Minneapolis, Minnesota, United States of America; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.9 Veterans Affairs Medical Center, Washington, D. C., United States of America.10 Hospital JM Ramos Mejia, Buenos Aires, Argentina.11 University of Würzburg Medical Center, Würzburg, Germany.12 Fundación Centro de Estudios Infectológicos, Buenos Aires, Argentina.13 Centre for Sexual Health & HIV Research, University College London, London, United Kingdom.14 unknown
BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.