IntroductionThe 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 MethodsA 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.ResultsNone 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.DiscussionNo 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.

Infliximab, a monoclonal antibody directed against tumour necrosis factor-alpha, is an effective therapy for Crohn's disease. Though uncommon, serious opportunistic infections, including reactivation of tuberculosis, have occurred in patients after infliximab administration.Meningitis caused by Listeria monocytogenes developed in a 37-year-old man six days after the second infusion of infliximab. The patient, who also was treated with azathioprine and corticosteroids, had an uneventful recovery after a course of antibiotics. Several other recent reports have implicated infliximab therapy in the development of severe Listeria infections, particularly meningitis and sepsis. With the increasing use of tumour necrosis factor-alpha-neutralizing agents, clinicians should be aware of the risk of opportunistic infections caused by L monocytogenes in patients with Crohn's disease following infliximab treatment.