Impact of HIV Infection on Immunologic, Transcriptomic, and Metabolomic Signatures

What is the purpose of this trial?

Aim 1: To elucidate differences in immunologic, transcriptomic and metabolomic signatures that differentiate HIV-positive vs. HIV-negative PWID with opiate use disorders (OUD) initiated on MAT. Subaim 1a: To elucidate cellular signatures associated with MAT in the context of HIV: We will carry out whole blood analyses of innate and adaptive immune cell populations (B cells, T cells, monocytes, dendritic cells, natural killer (NK) cells) via mass cytometry (CyTOF), including novel studies of platelet function, on samples obtained prior to and following the initiation of MAT among HIV+ and age-matched HIV- PWID with DSM-5-defined OUDs. These studies will allow us to evaluate the activation of multiple cell lineages and the extent of cytokine production as measured by intracellular cytokine staining (ICS), to determine the degree of chronic inflammation that may be associated with MAT agents. Subaim 1b: To elucidate alterations in innate immune receptor function in the context of MAT and HIV. We will also analyze innate immune pattern recognition receptor (PRR) function┬┐including Toll-like Receptor (TLR), NOD-like receptor (NLR) and RIG-I-like Receptor (RLR) function in monocytes and dendritic cells, using methods familiar to our group, including mass cytometry and ICS 1-6, to assess mechanisms underlying immune response dysregulation that may contribute to alterations in serum and plasma inflammatory biomarkers. Subaim 1c: To elucidate gene expression and metabolomic signatures of MAT in the context of HIV. We will leverage our previous experience with transcriptomic analyses of age-related changes in gene expression and metabolomics analyses (using the gas chromatography/mass spectroscopy (GC/MS) and liquid chromatography/MS (LC-MS/MS) platforms at the Broad Institute) in the context of influenza vaccine response to identify differential effects of methadone and buprenorphine MAT, and will employ state-of-the-art computational methods to integrate these signatures for a comprehensive view of the biology of these MAT agents. We will also generate validation and discovery cohorts to confirm newly generated models, as required by the RFA.


Participation Guidelines

Ages: 18 years and older

Gender: Both


National Institutes of Health

Dates: 04/01/2017 - 09/01/2021

Last Updated: 08/04/2017

Study HIC#: 1608018239

Get Involved

For more information about this study, contact:
Breanne E Biondi
+1 203-785-6175
breanne.biondi@yale.edu

If you would prefer to contact a member of the Help us Discover team about this trial and other similar trials, please email helpusdiscover@yale.edu or call 1-877-978-8348.

Trial Image

Investigators

Sandra Ann Springer

Principal Investigator

Sub-Investigators