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/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). 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.
Marchetti G, Cozzi Lepri A, Merlini E, Bellistrì GM, Castagna A, Galli M, et al. (2011). Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count. AIDS, 25(11), 1385-1394 [10.1097/QAD.0b013e3283471d10].
Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count
VERUCCHI, GABRIELLA;
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/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). 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
