Association of microbial translocation biomarkers with clinical outcome in controllers HIV-infected patients

Background: A proportion of patients who spontaneously control viral load (controllers) experienced clinical progression. We hypothesized that microbial translocation would independently determine the rate of disease progression in controllers. Methods: sCD14, lipopolysaccharide-binding protein (LBP) and EndoCab levels were assessed in 114 antiretroviral-naive patients with CD4(+) T cells above 500 cells/ml (including 63 controllers and 51 noncontrollers). The independent predictive value of these markers on time to progression to the combined endpoint of AIDS, non-AIDS event, initiation of combination antiretroviral therapy (cART) or CD4(+) cell count less than 500 cells/ml was assessed using a Cox regression model. Results: Most of the patients progressed to a combined endpoint (60%). Clinical progression in controllers was significantly lower than in noncontrollers (P = 0.02). Controllers with lower than the median baseline CD4(+) T-cell count and higher than the median baseline viral load, sCD14 and EndoCab levels had a worse prognosis (P<0.0001, P = 0.007, P = 0.05 and P = 0.012), while noncontrollers with higher than the median baseline LBP level also had a worse prognosis (P = 0.019). sCD14 and LBP increased and EndoCab decreased over time [from baseline (median values: 1486, 17604 ng/ml and 68 MMU/ml, respectively, to the date of event or the last determination (median values: 1663, 20230 ng/ml and 49 MMU/ml), respectively] in controllers (P = 0.04, 0.08 and 0.0006, respectively). Conclusion: Microbial translocation seems to be an important determinant of clinical progression in HIV-infected controllers independently of viremia. Measures to improve the intestinal mucosa damage or decrease translocation could influence the outcome in these patients. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.