Clinical trial NCT03976258: Effect of Heroin Use on Immune Activation and Cardiovascular Risk in HIV
Official title: The Impact of Intravenous Heroin Use on Immune Activation in Treated HIV
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infection
Opioid-use Disorder
Cardiovascular Diseases
Keywords: heroin
HIV
inflammation
cardiovascular
Lead sponsor: MetroHealth Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2019-06-05
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma soluble CD14 concentration
timeFrame: 48 weeks
measure: Change in Endopat measure of microvascular function
timeFrame: 48 weeks
measure: Change in target to background ratio measured by fluorodeoxyglucose (FDG)-positron emission tomography (PET)
timeFrame: 48 weeks
measure: Change in plasma Interferon Gamma-Induced Protein 10 concentration
timeFrame: 48 weeks
measure: Change in plasma intestinal fatty acid binding protein concentration
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in total fat stores measured by Whole body Dual-energy X-ray absorptiometry
timeFrame: 48 weeks
measure: Change in aortofemoral pulse wave velocity
timeFrame: 48 weeks
measure: Change is waist to hip ratio
timeFrame: 48 weeks
measure: Change in body mass index
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Metrohealth Medical center
state: Ohio
Study officials:
affiliation: MetroHealth Medical Center
name: Corrilynn O Hileman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospitals Cleveland Medical Center
name: Grace A McComsey, MD
role: PRINCIPAL_INVESTIGATOR
References: