Anti-retroviral Therapy, Medications for Opioid Use Disorder, Opioids and HIV Infection - Study 1

Summary

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Description

The use of intravenous opioids (e.g., heroin) has been shown to impair the immune reconstitution outcomes of combined antiretroviral therapy (cART) in HIV-1-infected individuals. People who inject opioid drugs (PWID) have lower CD4 count recovery and sustained cellular activation and inflammation co...

The use of intravenous opioids (e.g., heroin) has been shown to impair the immune reconstitution outcomes of combined antiretroviral therapy (cART) in HIV-1-infected individuals. People who inject opioid drugs (PWID) have lower CD4 count recovery and sustained cellular activation and inflammation compared to non-opioid users. The pathogenesis of this phenomenon remains understudied. Notably, the effect of oral ?-opioid receptor (MOR) full agonists (e.g., methadone) or partial agonist (e.g., buprenorphine), which are widely used as medications for opioid use disorder treatment, on cART-mediated immune reconstitution is also unknown, limiting the information available to healthcare providers on immune or viral outcomes associated with MOR agonists or antagonists (e.g., naltrexone) in HIV-infected PWIDs. The primary objective of this proposal is to establish the extent and pathogenesis of residual immune activation/inflammation, levels of immune reconstitution, and HIV measures in HIV-1-infected PWID who start cART concomitant with medication for opioid use disorder in an addiction clinic with three strategies: a) integrated treatment program (ITP) with oral methadone maintenance, or b) ITP with oral buprenorphine, or c) ITP with extended-release naltrexone. The primary hypothesis is that PWIDs receiving MOR agonists (i.e. methadone maintenance) will have impaired cART-mediated immune reconstitution outcomes and/or higher levels of systemic immune activation and cell-associated HIV as compared to PWIDs receiving MOR partial agonist (i.e., buprenorphine/naloxone) or antagonist (i.e., extended-release naltrexone). The investigators will test these hypotheses in the following specific aims: Specific Aim 1: To define the impact of sustained MOR stimulation on the kinetics and extent of immune reconstitution and activation in HIV-1-infected PWID who are starting cART. To this end, the investigators will compare long-term changes in immune activation and senescence, systemic inflammation, and biological immune reconstitution parameters in a cohort of PWID with chronic HIV infection initiating ART, randomized 1:1:1 to either methadone, buprenorphine/naloxone or extended-release naltrexone. Specific Aim 2: To define the clinical and virological correlates of long-term treatment with MOR full agonist (methadone), partial agonist (buprenorphine/naloxone) and antagonist (extended-release naltrexone), by analysis of clinical outcomes (CD4 count), adherence to ART, and retention in care. Viral measures will focus on the changes in persistent HIV reservoir measures on ART (i.e., characterization of cell-associated viral RNA and DNA species in PBMC).

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