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

NCT03976258 | Completed

• 2 other identifiers: IRB17-00336 and IRB17-004291R01DA044576-01
• Study Type: observational
• Target: 190
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV Infection; Opioid-use Disorder; Cardiovascular Diseases

Keywords

heroin; HIV; inflammation; cardiovascular

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• Change in total fat stores measured by Whole body Dual-energy X-ray absorptiometry

  48 weeks

• Change in aortofemoral pulse wave velocity

  48 weeks

• Change is waist to hip ratio

  48 weeks

• Change in body mass index

  48 weeks

Study Arms (8)

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

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

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

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

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

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

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

Interventions

buprenorphine/naloxone DRUG

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 buprenorphine/naloxone; HIV-uninfected adults initiating buprenorphine/naloxone

Methadone DRUG

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 methadone; HIV-uninfected adults initiating methadone

Naltrexone Injection DRUG

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.

Also known as: Vivitrol

HIV-infected adults initiating Vivitrol; HIV-uninfected adults initiating Vivitrol

Heroin DRUG

This is an observational study. Participants using heroin will be enrolled into this group.

HIV-infected adults actively using heroin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• HIV infection or no HIV infection
• 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

You may not qualify if:

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

Sponsors & Collaborators

• MetroHealth Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Metrohealth Medical center

Cleveland, Ohio, 44109, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, serum, urine, stool, peripheral blood mononuclear cells

MeSH Terms

Conditions

HIV Infections; Opioid-Related Disorders; Cardiovascular Diseases; Inflammation

Interventions

Buprenorphine, Naloxone Drug Combination; Methadone; Naltrexone; vivitrol; Heroin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Ketones; Organic Chemicals; Morphine Derivatives

Study Officials

• Corrilynn O Hileman, MD

  MetroHealth Medical Center

  PRINCIPAL INVESTIGATOR

• Grace A McComsey, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: June 5, 2019
• Study Start: July 14, 2017
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: October 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)