Evidence of cryptic replication in dolutegravir intensification data
Project Summary / Abstract: The primary research objective of this project is to validate our models of cryptic HIV replication during antiretroviral therapy using data from a recently completed dolutegravir intensification trial. We have developed these models using data from two raltegravir intensification experiments; however, the data from these previous experiments was sparse in time, and only group-level statistical validation was possible. The data from this trial is rich in both number of patients and number of time points, and will allow us to validate the predicted relationship between pre-intensification ongoing cryptic replication and post-intensification 2-LTR episome dynamics at the individual patient level, and to explore correlations between the calculated pre-intensification replication and other blood-borne markers of inflammation. In addition, the trial will allow us to validate our recently developed method of information-optimal experiment design by calculating the information provided by this experiment and comparing it to the information content predicted for this study design by our optimization method. If the data from this trial validates our model predictions, we will have confirmed the presence of ongoing efficient replication in a subset of treated HIV patients with no detectable plasma viremia, and we will have validated a minimally invasive method of detecting this cryptic replication through a clinical intervention.