TY - JOUR
T1 - Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection
T2 - A case control study
AU - Murray, Daniel D.
AU - Suzuki, Kazuo
AU - Law, Matthew
AU - Trebicka, Jonel
AU - Wentworth, Deborah
AU - Johnson, Margaret
AU - Vjecha, Michael J.
AU - Kelleher, Anthony D.
AU - Emery, Sean
AU - Aagaard, B.
AU - Aragon, E.
AU - Arnaiz, J.
AU - Borup, L.
AU - Clotet, B.
AU - Dragsted, U.
AU - Fau, A.
AU - Gey, D.
AU - Grarup, J.
AU - Hengge, U.
AU - Herrero, P.
AU - Jansson, P.
AU - Jensen, B.
AU - Jensen, K.
AU - Juncher, H.
AU - Lopez, P.
AU - Lundgren, J.
AU - Matthews, C.
AU - Mollerup, D.
AU - Pearson, M.
AU - Phillips, A.
AU - Reilev, S.
AU - Tillmann, K.
AU - Varea, S.
AU - Angus, B.
AU - Babiker, A.
AU - Cordwell, B.
AU - Darbyshire, J.
AU - Dodds, W.
AU - Fleck, S.
AU - Collins, G.
AU - Denning, E.
AU - Neaton, J.
AU - Wentworth, D.
AU - Wyman, N.
AU - Lifson, A.
AU - Grund, B.
AU - Neuhaus, J.
AU - Duprez, D.
AU - Henry, W. K.
AU - INSIGHT ESPRIT and SMART Study Groups
N1 - Publisher Copyright:
© This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2015/10/14
Y1 - 2015/10/14
N2 - Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.
AB - Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.
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U2 - 10.1371/journal.pone.0139981
DO - 10.1371/journal.pone.0139981
M3 - Article
C2 - 26465293
AN - SCOPUS:84949225661
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 10
M1 - e0139981
ER -
