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

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

Rethinking the Threats to Scientific Balance in Contexts of Litigation and Regulation

BACKGROUND: Although existing literature does discuss difficulties of doing science in contexts of litigation and regulation, work to date reflects little first-hand experience in such contexts. This gap is understandable but also potentially troubling: Concerns that seem important from afar may or may not match those that are most salient for scientists actually engaged in such work.OBJECTIVES: Drawing on experience on scientific committees and in lawsuits, and using skills developed through doing qualitative fieldwork, I reanalyze past experiences and field notes from the perspective of the 2006 Coronado Conference "Truth and Advocacy in Contexts of Litigation and Regulation." Although I initially shared the kinds of concerns generally stressed by other scientists and science-studies scholars-emphasizing overt, relatively sinister efforts to limit scientific objectivity-neither the literature nor my initial instincts provided adequate preparation for more subtle influences, which actually created stronger pressures toward bias. Particularly unexpected pressures came from consistent deference and praise for independence and credibility.DISCUSSION AND CONCLUSIONS: The cases discussed in this article are by nature suggestive, not definitive; additional research is dearly needed. Future research, however, needs to focus not just on pressures toward bias that are easy to imagine, but also on those that are easy to overlook