title: HIV infection rather than concurrent opportunistic infections drives most systemic procoagulant, vascular and damage responses - a prospective cohort study in central Africa.
abstract: BACKGROUND
  HIV infection is accompanied by various systemic host responses, including activation of coagulation and the vascular endothelium. We sought to determine the impact of opportunistic coinfections in a central African setting.
  
  
  METHODS
  This prospective study included 98 HIV-infected individuals in Gabon initiating combination antiretroviral therapy (cART) and followed them up for 6 months. Patients were stratified according to the presence of active tuberculosis (TB; n=19), mucocutaneous opportunistic infection (n=9) or no opportunistic infection (n=70). HIV-uninfected subjects were included as controls (n=32). Plasma concentrations of 14 markers of coagulation, endothelial activation, extracellular matrix formation and tissue damage were measured with a multiplex assay at baseline and months 3 and 6 after cART initiation.
  
  
  RESULTS
  HIV-infected patients showed elevated plasma levels of all biomarkers measured with exception of protein C, which was reduced. Concurrent TB was only associated with elevated concentrations of D-dimer, metallopeptidase inhibitor 1 and Tenascin-C. Mucocutaneous coinfection did not alter HIV-associated responses. Most markers measured declined but remained elevated despite response to cART.
  
  
  CONCLUSIONS
  HIV infection is associated with systemic pro-coagulant, vascular and damage responses. In an ambulatory setting, concurrent opportunistic infections have little if any influence on these responses and normalization is incomplete after response to cART. This suggests that these responses are mainly driven by HIV-associated immune activation and less so by opportunistic infections.
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Centre de Recherches Médicales de Lambaréné, Albert Schweitzer Hospital, Lambaréné, Gabon.|Centre de Traitement Ambulatoire, Lambaréné, Gabon.|Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Saskia
authors.initials: S
authors.lastname: Janssen
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Centre de Recherches Médicales de Lambaréné, Albert Schweitzer Hospital, Lambaréné, Gabon.
authors.forename: Michaela Am
authors.initials: MA
authors.lastname: Huson
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Centre de Recherches Médicales de Lambaréné, Albert Schweitzer Hospital, Lambaréné, Gabon.|Centre de Traitement Ambulatoire, Lambaréné, Gabon.
authors.forename: Kara K
authors.initials: KK
authors.lastname: Osbak
authors.affiliation: Centre de Traitement Ambulatoire, Lambaréné, Gabon.
authors.forename: Elie-Gide
authors.initials: EG
authors.lastname: Rossatanga
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Albert Schweitzer Hospital, Lambaréné, Gabon.
authors.forename: Abraham
authors.initials: A
authors.lastname: Alabi
authors.affiliation: Departments of Respiratory Medicine and Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Centre de Recherches Médicales de Lambaréné, Albert Schweitzer Hospital, Lambaréné, Gabon.|Centre de Traitement Ambulatoire, Lambaréné, Gabon.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005681:Gabon; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D009894:Opportunistic Infections / Q000097:blood* / Q000175:diagnosis; D011446:Prospective Studies; D019063:Tenascin / Q000097:blood; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D019063:Tenascin; C036309:fibrin fragment D; D002097:C-Reactive Protein