Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4 + cell count

Giulia Marchetti, Alessandro Cozzi-Lepri, Esther Merlini, Giusi M. Bellistrì, Antonella Castagna, Massimo Galli, Gabriella Verucchi, Andrea Antinori, Andrea Costantini, Andrea Giacometti, Antonino Di Caro, Antonella D'Arminio Monforte

Research output: Contribution to journalArticle

Abstract

Objectives: 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 ACD4 + cell count. Design: 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 ACD4 + 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, ACD4 + and plasma HIV-RNA was evaluated by linear regression and nonparametric Spearmans rho. The independent predictive value of these markers on time to progression to the combined endpoint of AIDS, death, ACD4 + 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, 110pg/ml (IQR 75-215), sCD14, 3.3μg/ml (2.2-4.8), IL-6, 1.1pg/ml (0.6-1.9) and TNF-α, 2.4pg/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% ACD4 + 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 ACD4 + (relative hazard=1.40 per loge higher, 95% confidence interval 1.18-1.66, P+ cell count and HIV viraemia and may be considered a candidate biomarker for HIV monitoring and evaluation in clinical trials.

Original languageEnglish
Pages (from-to)1385-1394
Number of pages10
JournalAIDS (London, England)
Volume25
Issue number11
DOIs
Publication statusPublished - Jul 17 2011

Keywords

  • HIV
  • immune activation
  • lipopolysaccharide
  • microbial translocation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Marchetti, G., Cozzi-Lepri, A., Merlini, E., Bellistrì, G. M., Castagna, A., Galli, M., Verucchi, G., Antinori, A., Costantini, A., Giacometti, A., Di Caro, A., & D'Arminio Monforte, A. (2011). Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4 + cell count. AIDS (London, England), 25(11), 1385-1394. https://doi.org/10.1097/QAD.0b013e3283471d10