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

The Impact of Intravenous Heroin Use on Immune Activation in Treated HIV

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.

Study Overview

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

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 Type: Observational
• Enrollment (Actual): 190

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults ages 18 to 80 years with and without HIV infection using heroin or initiating treatment for heroin use or not using heroin.

Description

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIV-infected adults actively using 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.	Drug: Heroin; This is an observational study. Participants using heroin will be enrolled into this group.
HIV-infected adults never having used heroin; HIV-infected adults on antiretroviral therapy matched to HIV-infected adults actively using heroin by age, sex and CD4+ count.
HIV-infected adults initiating 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.	Drug: buprenorphine/naloxone; This is an observational study. Buprenorphine/naloxone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-uninfected adults initiating 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.	Drug: buprenorphine/naloxone; This is an observational study. Buprenorphine/naloxone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-infected adults initiating 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	Drug: Methadone; This is an observational study. Methadone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-infected adults initiating Vivitrol; 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.	Drug: Naltrexone Injection; This is an observational study. Naltrexone injection for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.; Other Names: Vivitrol
HIV-uninfected adults initiating 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.	Drug: Methadone; This is an observational study. Methadone for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.
HIV-uninfected adults initiating Vivitrol; 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.	Drug: Naltrexone Injection; This is an observational study. Naltrexone injection for opioid use disorder will be provided in a standardized way by experienced providers through already established funded treatment programs.; Other Names: Vivitrol

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: MetroHealth Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Corrilynn O Hileman, MD, MetroHealth Medical Center; Principal Investigator: Grace A McComsey, MD, University Hospitals Cleveland Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2017
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: June 4, 2019
• First Posted (Actual): June 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: HIV; inflammation; cardiovascular; heroin
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Cardiovascular Diseases; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Respiratory System Agents; Alcohol Deterrents; Antitussive Agents; Buprenorphine; Naltrexone; Naloxone; Buprenorphine, Naloxone Drug Combination; Methadone; Heroin
• Other Study ID Numbers: IRB17-00336 and IRB17-00429; 1R01DA044576-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No