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

'Walking Along Beside the Researcher': How Canadian REBs/IRBs ar eResponding to the Needs of Community-Based Participatory Research

research ethics boards and institutional review boards (REBs/IRBs) have been criticized for relying on conceptions of research that privilege biomedical, clinical, and experimental designs, and for penalizing research that deviates from this model. Studies that use a community-based participatory research (CBPR) design have been identified as particularly challenging to navigate through existing ethics review frameworks. However, the voices of REB/IRB members and staff have been largely absent in this debate. The objective of this article is to explore the perspectives of members of Canadian university-based REBs/IRBs regarding their capacity to review CBPR protocols. We present findings from interviews with 24 Canadian REB/IRB members, staff, and other key informants. Participants were asked to describe and contrast their experiences reviewing studies using CBPR and mainstream approaches. Contrary to the perception that REBs/IRBs are inflexible and unresponsive, participants described their attempts to dialogue and negotiate with researchers and to provide guidance. Overall, these Canadian REBs/IRBs demonstrated a more complex understanding of CBPR than is typically characterized in the literature. Finally, we situate our findings within literature on relational ethics and explore the possibility of researchers and REBs/IRBs working collaboratively to find solutions to unique ethical tensions in CBP

Pathways From HIV-Related Stigma to Antiretroviral Therapy Measures in the HIV Care Cascade for Women Living With HIV in Canada

Associations between HIV-related stigma and reduced antiretroviral therapy (ART) adherence are widely established, yet the mechanisms accounting for this relationship are underexplored. There has been less attention to HIV-related stigma and its associations with ART initiation and current ART use. We examined pathways from HIV-related stigma to ART initiation, current ART use, and ART adherence among women living with HIV in Canada