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

The purpose of this study is to understand changes in how your blood cells, genes, metabolism, and immune system work after you begin medication assisted therapy (MAT) (e.g. buprenorphine/naloxone, buprenorphine, methadone or extended-release naltrexone), for treatment of an opioid use disorder. The researchers will follow all participants and schedule regular interviews and blood draws to gather information. This will enable them to look at the presence of specific factors associated with treatment for opioid use disorder in those living with HIV infection and those without HIV infection. The study will last for 6 months.

Age18 years and older
GenderBoth

Contact Us

For more information about this study, including how to volunteer, contact:

Sandra Ann Springer

sandra.springer@yale.edu

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Trial Purpose and Description

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.

Eligibility Criteria

We are currently looking for persons who:

Are 18 years of age or older Have a history of problems with opioid drugs (heroin or prescription pain medications) but have NOT STARTED treatment

Speaks English or Spanish