title: Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count.
abstract: OBJECTIVE
  We investigated the significance of microbial translocation measured on average 3 years after HIV seroconversion in driving disease progression in HIV untreated patients with high CD4(+) cell count.
  
  
  METHODS
  We included ICONA patients with documented last HIV-negative and first HIV-positive test, at least one plasma sample stored while antiretroviral therapy (ART)-naive and CD4(+) cell count greater than 200 cells/μl.
  
  
  METHODS
  Microbial translocation [lipopolysaccharide (LPS), sCD14 and EndoCAb] and immune activation (IL-6 and TNF-α) were measured. Correlation between immune activation, microbial translocation, CD4(+) and plasma HIV-RNA was evaluated by linear regression and nonparametric Spearman's rho. The independent predictive value of these markers on time to progression to the combined endpoint of AIDS, death, CD4(+) cell count less than 200 cells/μl or start of antiretroviral therapy (ART) was assessed using survival analysis.
  
  
  RESULTS
  We analysed 1488 biomarker measures from 379 patients. A median of 3.1 years after the estimated seroconversion date [interquartile range (IQR) 1.6-5.4], median (IQR) markers values were LPS, 110 pg/ml (IQR 75-215), sCD14, 3.3 μg/ml (2.2-4.8), IL-6, 1.1 pg/ml (0.6-1.9) and TNF-α, 2.4 pg/ml (1.8-3.4). Two hundred and sixty progression events were recorded over a median of 1.6 years from the first sample (2% AIDS, 84% ART initiation, 12% CD4(+) cell count less than 200 cells/μl and 2% death). LPS was the only biomarker associated with this primary composite outcome independently of age, HIV-RNA and CD4(+) (relative hazard = 1.40 per loge higher, 95% confidence interval 1.18-1.66, P < 0.001).
  
  
  CONCLUSIONS
  Circulating LPS in the first years of chronic HIV infection is a strong predictor of disease progression independent of CD4(+) cell count and HIV viraemia and may be considered a candidate biomarker for HIV monitoring and evaluation in clinical trials.
authors.affiliation: Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, 'San Paolo' Hospital, University of Milan, Italy. giulia.marchetti@unimi.it
authors.forename: Giulia
authors.initials: G
authors.lastname: Marchetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Esther
authors.initials: E
authors.lastname: Merlini
authors.forename: Giusi M
authors.initials: GM
authors.lastname: Bellistrì
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Verucchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Andrea
authors.initials: A
authors.lastname: Costantini
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.forename: Antonino
authors.initials: A
authors.lastname: di Caro
authors.forename: Antonella
authors.initials: A
authors.lastname: D'arminio Monforte
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D050296:Microbial Viability / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult