So how good is TILDA in measuring HIV

So how good is TILDA in measuring HIV that is capable of replicating? The frequency of CD4+ T raas inhibitor with inducible RNA by TILDA is within the realm of expectation. First, early treated individuals harbor fewer such cells than chronically treated individuals. Second, the size of inducible virus by TILDA is smaller than HIV DNA by PCR but larger than replication competent virus by VOA, suggesting that TILDA is measuring the induction of more intact proviruses than the standard VOA assay. However, TILDA does not directly measure virus production, either infectious or non-infectious, but rather, it measures inducible multi-spliced transcripts, which is quite proximal to virion release. As the authors note, it is possible that cells with inducible multiply-spliced transcripts may not produce infectious virus particles. Indeed, the results of the TILDA assay and the VOA performed on the same samples show a weak, non-significant correlation. Whether this is due to limitations of the TILDA or VOA is unclear and will require further study. Lymphoid tissues are also major HIV reservoir sites (), and it is possible that TILDA, because of its small sample requirement, could be used to measure inducible proviruses in tissue samples. This possibility would be a significant advance given that a sensitive VOA cannot be performed with the limited number of cells available from tissue samples. TILDA could be a research tool for in vitro screening of drugs such as latency reversing agents for further animal and human trials, and measuring the effects of these drugs in vivo. As testing for HIV remission will require ART interruption (), TILDA could be used to identify trial participants with the highest potential for achieving remission (i.e. have no inducible RNA by TILDA). These potential uses require further validation. Future studies should include TILDA as one of the outcome measures of differing interventions (latency reversing agents, immunotherapeutics, gene- and cell-based therapies) and in different patient populations (virally suppressed acutely and chronically infected, children and adults) to assess the broad utility of TILDA. If TILDA or other novel assays can predict the duration of HIV remission off ART, it will accelerate progress towards a cure of HIV.
(MTB) is a major microbial pathogen that threatens global health. The WHO has estimated about 9 million new tuberculosis (TB) cases and around 1.5 million deaths due to TB in the year 2013 (). In MTB-infected individuals, bacteria may exist in a dormant state for lengthy periods without causing disease symptoms, or may finally start multiplying and evading immune control, resulting in active TB in 5–10% of infected cases. At present, factors that promote progression from latent tuberculosis infection (LTBI) to disease are not totally understood. Therefore, management of LTBI plays a significant role for TB disease control given that quiescent bacilli are a big reservoir of potential TB cases. Tuberculin skin test (TST) has been the classical method used for LTBI diagnosis in spite of its compromised specificity due to cross-reaction with bacillus Calmette–Guérin (BCG) vaccine strain and non-tuberculous mycobacteria. Furthermore, it has low sensitivity in immune compromised patients, who are in particular those that mainly need this test because they have a high risk of developing active TB if they are infected. Interferon (IFN)-γ release assays (IGRAs) appeared more than a decade ago as an alternative method to TST for diagnosing LTBI. They detect the IFN-γ released by sensitized T cells after stimulation with specific MTB antigens encoded in the region of difference (RD) 1 and 11 (ESAT-6, CFP-10 and TB7.7) (). Nowadays, IGRAs implementation has improved LTBI diagnosis because of their higher specificity with respect to TST and good correlation with MTB exposure degree; however, they do not discriminate between LTBI and active TB (). As a consequence, there is a need for studying new biomarkers to explore the biology and the immune response for distinguishing latency from disease.