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

MetroHealth Medical Center

Status: Completed

Conditions: Opioid-use Disorder; HIV Infection; Cardiovascular Diseases

Treatments: Drug: Heroin; Drug: Methadone; Drug: Naltrexone Injection; Drug: buprenorphine/naloxone

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT03976258

1R01DA044576-01 (U.S. NIH Grant/Contract)

IRB17-00336 and IRB17-00429

Details and patient eligibility

About

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.

Full 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.

Enrollment: 190 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

190 participants in 8 patient groups

HIV-infected adults actively using heroin

Description:

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.

Treatment:

Drug: Heroin

HIV-infected adults never having used heroin

Description:

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

Description:

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.

Treatment:

Drug: buprenorphine/naloxone

HIV-uninfected adults initiating buprenorphine/naloxone

Description:

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.

Treatment:

Drug: buprenorphine/naloxone

HIV-infected adults initiating methadone

Description:

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

Treatment:

Drug: Methadone

HIV-infected adults initiating Vivitrol

Description:

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.

Treatment:

Drug: Naltrexone Injection

HIV-uninfected adults initiating methadone

Description:

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.

Treatment:

Drug: Methadone

HIV-uninfected adults initiating Vivitrol

Description:

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.

Treatment:

Drug: Naltrexone Injection