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 CD4(+) 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 CD4(+) cell count greater than 200 cells/mu l. Methods: Microbial translocation [lipopolysaccharide (LPS), sCD14 and EndoCAb] and immune activation (IL-6 and TNF-alpha) 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/mu l 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 mu g/ml (2.2-4.8), IL-6, 1.1 pg/ml (0.6-1.9) and TNF-alpha, 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/mu l 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 log(e) higher, 95% confidence interval 1.18-1.66, P<0.001). Conclusion: 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.

Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count / G.C. Marchetti, A. Cozzi-Lepri, E. Merlini, G.M. Bellistrì, A. Castagna, M. Galli, G. Verucchi, A. Antinori, A. Costantini, A. Giacometti, A. di Caro, A. Dʼarminio Monforte. - In: AIDS. - ISSN 0269-9370. - 25:11(2011 Jul 17), pp. 1385-1394.

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

G.C. Marchetti
Primo
;
E. Merlini;G.M. Bellistrì;M. Galli;A. Dʼarminio Monforte
Penultimo
;
2011

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 CD4(+) 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 CD4(+) cell count greater than 200 cells/mu l. Methods: Microbial translocation [lipopolysaccharide (LPS), sCD14 and EndoCAb] and immune activation (IL-6 and TNF-alpha) 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/mu l 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 mu g/ml (2.2-4.8), IL-6, 1.1 pg/ml (0.6-1.9) and TNF-alpha, 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/mu l 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 log(e) higher, 95% confidence interval 1.18-1.66, P<0.001). Conclusion: 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.
HIV; immune activation; lipopolysaccharide; microbial translocation
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/169069
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