title: Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities.
abstract: OBJECTIVE
  HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation.
  
  
  METHODS
  Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142).
  
  
  RESULTS
  Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07).
  
  
  CONCLUSIONS
  After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease.
authors.affiliation: Inserm UMRS1018, CESP, Epidemiology of HIV and STI, Le Kremlin-Bicêtre, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Ghislain
authors.affiliation: Tenon Hospital, AP-HP, Department of Biochemistry and Hormonology, Paris, France.|Inserm UMRS 938, Centre de Recherche Saint-Antoine, Paris, France.|Sorbonne Universities, UPMC, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bastard
authors.affiliation: Inserm UMRS1018, CESP, Epidemiology of HIV and STI, Le Kremlin-Bicêtre, France.|Paris-Sud university, Le Kremlin-Bicêtre, France.|Bicêtre Hospital, AP-HP, Department of Public Health, Le Kremlin-Bicêtre, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: Tenon Hospital, AP-HP, Department of Biochemistry and Hormonology, Paris, France.|Inserm UMRS 938, Centre de Recherche Saint-Antoine, Paris, France.|Sorbonne Universities, UPMC, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.affiliation: Tenon Hospital, AP-HP, Department of Biochemistry and Hormonology, Paris, France.|Inserm UMRS 938, Centre de Recherche Saint-Antoine, Paris, France.|Sorbonne Universities, UPMC, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
authors.forename: Soraya
authors.initials: S
authors.lastname: Fellahi
authors.affiliation: Saint-Louis Hospital, AP-HP, Department of Clinic Immunopathology, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.affiliation: Teaching hospital of Nancy, Brabois Hospitals, Department of Infectious and Tropical Diseases, Vandoeuvre les Nancy, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: May
authors.affiliation: Pitié-Salpétrière Hospital, AP-HP, Department of Internal Medicine and Clinical Immunology, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.affiliation: Inserm UMRS 938, Centre de Recherche Saint-Antoine, Paris, France.|Sorbonne Universities, UPMC, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.|Saint-Antoine Hospital, AP-HP, Common Laboratory of Biology and Molecular Genetics, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Vigouroux
authors.affiliation: Inserm UMRS1018, CESP, Epidemiology of HIV and STI, Le Kremlin-Bicêtre, France.|Paris-Sud university, Le Kremlin-Bicêtre, France.|Bicêtre Hospital, AP-HP, Department of Internal Medicine, Le Kremlin-Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D005260:Female; D015497:HIV-1; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D047889:Receptors, Tumor Necrosis Factor, Type II; D002097:C-Reactive Protein