Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

INSIGHT ESPRIT and SMART Study Groups

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0139981
JournalPLoS One
Volume10
Issue number10
DOIs
StatePublished - Oct 14 2015
Externally publishedYes

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Biomarkers
Human immunodeficiency virus 1
case-control studies
MicroRNAs
microRNA
HIV Infections
HIV-1
Case-Control Studies
biomarkers
Chemical activation
therapeutics
Mortality
Serum
infection
T-cells
CD4 Lymphocyte Count
T-lymphocytes
Therapeutics
human diseases
interleukin-6

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection : A case control study. / INSIGHT ESPRIT and SMART Study Groups.

In: PLoS One, Vol. 10, No. 10, e0139981, 14.10.2015.

Research output: Contribution to journalArticle

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title = "Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study",
abstract = "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.",
author = "{INSIGHT ESPRIT and SMART Study Groups} and Murray, {Daniel D.} and Kazuo Suzuki and Matthew Law and Jonel Trebicka and Jacquie Neuhaus and Deborah Wentworth and Margaret Johnson and Vjecha, {Michael J.} and Kelleher, {Anthony D.} and Sean Emery and B. Aagaard and E. Aragon and J. Arnaiz and L. Borup and B. Clotet and U. Dragsted and A. Fau and D. Gey and J. Grarup and U. Hengge and P. Herrero and P. Jansson and B. Jensen and K. Jensen and H. Juncher and P. Lopez and J. Lundgren and C. Matthews and D. Mollerup and M. Pearson and A. Phillips and S. Reilev and K. Tillmann and S. Varea and B. Angus and A. Babiker and B. Cordwell and J. Darbyshire and W. Dodds and S. Fleck and J. Horton and F. Hudson and Y. Moraes and F. Pacciarini and A. Palfreeman and N. Paton and N. Smith and {Van Hooff}, F. and Terri Schmidt and Mary O'Hearn",
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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 - INSIGHT ESPRIT and SMART Study Groups

AU - Murray, Daniel D.

AU - Suzuki, Kazuo

AU - Law, Matthew

AU - Trebicka, Jonel

AU - Neuhaus, Jacquie

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 - Horton, J.

AU - Hudson, F.

AU - Moraes, Y.

AU - Pacciarini, F.

AU - Palfreeman, A.

AU - Paton, N.

AU - Smith, N.

AU - Van Hooff, F.

AU - Schmidt, Terri

AU - O'Hearn, Mary

PY - 2015/10/14

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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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