Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV

Completed

• Conditions: Cardiovascular Diseases; Opioid-use Disorder; HIV Infection
• Interventions: Drug: Naltrexone Injection; Drug: buprenorphine/naloxone; Drug: Methadone; Drug: Heroin

• Registration Number: NCT03976258
• Lead Sponsor: MetroHealth Medical Center

Brief Summary

Despite the advent of safer HIV therapies, high levels of markers of systemic inflammation and increased cardiovascular risk threaten the well-being of individuals living with HIV and present a significant challenge for HIV providers. These risks may be accentuated in HIV-infected individuals who are active intravenous drug users (IVDU); however, this population has been specifically excluded from prior studies assessing immune activation and cardiovascular risk in people living with HIV. In this study, the investigators will specifically target HIV-infected participants who are active IVDU, and co-enroll a control group of HIV-infected participants who never used IV drugs. The investigators will study the specific alterations in immune activation and several mechanisms felt to be potential drivers of immune activation outside of the IVDU population, namely gut integrity alteration, microbial translocation, and oxidized lipids. The investigators will also study the effect of IVDU on markers of arterial inflammation and vascular function. Importantly, the investigators will study the reversibility of immune activation, gut dysfunction, and cardiovascular markers after cessation of IVDU, and to that effect, compare strategies for IVDU cessation-buprenorphine/naloxone versus methadone or vivitrol maintenance treatment.

Detailed Description

This is a 48-week matched, prospective, observational, cohort study of HIV-infected adults on antiretroviral therapy who actively use heroin or who have never used heroin. The overarching goals are 1) to define the extent and specifics of immune activation in HIV-infected IV heroin users; 2) to define the effect of IV heroin on gut integrity and permeability, and the relationship of gut integrity alteration and immune activation; 3) importantly, to study the reversibility of immune activation, inflammation, and gut dysfunction after cessation of IV heroin, and to that effect, compare strategies for medication assisted treatment-buprenorphine/naloxone versus methadone or vivitrol maintenance; 4) to study if heightened immune activation associated with active intravenous drug use (IVDU) is associated with higher cardiovascular disease risk, including endothelial dysfunction and arterial inflammation, and if these effects are reversible with buprenorphine/naloxone or methadone.

Study Timeline

• Study Start: 2017-07-14
• Study First Submitted: 2018-07-12
• Study First Submitted QC: 2019-06-04
• Study First Posted: 2019-06-05
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-28
• Last Update Posted: 2023-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

• HIV infection or no HIV infection
• 18 years or older
• HIV-1 RNA < 400 if HIV-infected and on antiretroviral therapy
• On stable antiretroviral therapy at least 12 weeks with cumulative duration of at least a year for HIV-infected if on antiretroviral therapy
• Currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past for active heroin group
• Initiating medication assisted treatment for active heroin use initiating medication assisted treatment groups

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Exclusion Criteria

• Active infection, malignancy or other inflammatory condition
• Uncontrolled diabetes or hypothyroidism
• Known cardiovascular disease
• Pregnancy

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HIV-infected adults initiating Vivitrol	Naltrexone Injection	HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with Vivitrol.
HIV-uninfected adults initiating Vivitrol	Naltrexone Injection	HIV-uninfected adults who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with Vivitrol.
HIV-infected adults initiating buprenorphine/naloxone	buprenorphine/naloxone	HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with buprenorphine/naloxone.
HIV-uninfected adults initiating buprenorphine/naloxone	buprenorphine/naloxone	HIV-uninfected adults who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with buprenorphine/naloxone.
HIV-infected adults initiating methadone	Methadone	HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with methadone
HIV-uninfected adults initiating methadone	Methadone	HIV-uninfected adults who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past initiating medication assisted treatment (MAT) for opioid use disorder with methadone.
HIV-infected adults actively using heroin	Heroin	HIV-infected adults on antiretroviral therapy who are currently using heroin at least 1 month with a cumulative duration of at least 12 months in the past.

Primary Outcome Measures

Name	Time	Method
Change in plasma soluble CD14 concentration	48 weeks	soluble marker of monocyte activation
Change in plasma Interferon Gamma-Induced Protein 10 concentration	48 weeks	soluble marker of inflammation
Change in plasma intestinal fatty acid binding protein concentration	48 weeks	soluble marker of gut integrity
Change in Endopat measure of microvascular function	48 weeks	Measure of endothelial function
Change in target to background ratio measured by fluorodeoxyglucose (FDG)-positron emission tomography (PET)	48 weeks	Measure of vascular inflammation

Secondary Outcome Measures

Name	Time	Method
Change is waist to hip ratio	48 weeks	Measurement of central obesity
Change in aortofemoral pulse wave velocity	48 weeks	Measure of arterial stiffness
Change in total fat stores measured by Whole body Dual-energy X-ray absorptiometry	48 weeks	Measurement of fat stores
Change in body mass index	48 weeks	Body measurement

Trial Locations

Locations (2)

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

Metrohealth Medical center; 🇺🇸 Cleveland, Ohio, United States