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: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Murray
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.affiliation: Department of Internal Medicine, University of Bonn, Bonn, Germany.
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.affiliation: University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Jacquie
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Deborah
authors.initials: D
authors.lastname: Wentworth
authors.affiliation: Ian Charleson Day Centre, Royal Free Hampstead NHS Trust, London, United Kingdom.
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Institute for Clinical Research, Veterans Affairs Medical Center, Washington D.C., United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Vjecha
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D035683:MicroRNAs