Anti-retroviral Therapy, Medications for Opioid Use Disorder, Opioids and HIV Infection - Study 1 (AMOHI-1)

March 18, 2026 updated by: University of Pennsylvania

Effects of Mu-opiate Receptor Engagement on Microbial Translocation and Residual Immune Activation in HIV-infected, ART Suppressed Opioid Use Disorder Patients Initiating Medication-assisted Treatment

HIV infection, as well as exposure to opioids (including heroin), are associated with systemic immune activation including increased microbial translocation from the gut. The overall objective of this study is to define the impact of long-term mu-opiate receptor stimulation or blockage with medication for opiate use disorder (i.e, methadone, buprenorphine/naloxone, or extended-release naltrexone) on the kinetics and extent of immune reconstitution on HIV-1 infected people who inject opiate and initiating antiretroviral therapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The use of intravenous opioids (e.g., heroin) has been shown to impair the immune reconstitution outcomes of combined antiretroviral therapy (cART) in HIV-1-infected individuals. People who inject opioid drugs (PWID) have lower CD4 count recovery and sustained cellular activation and inflammation compared to non-opioid users. The pathogenesis of this phenomenon remains understudied. Notably, the effect of oral μ-opioid receptor (MOR) full agonists (e.g., methadone) or partial agonist (e.g., buprenorphine), which are widely used as medications for opioid use disorder treatment, on cART-mediated immune reconstitution is also unknown, limiting the information available to healthcare providers on immune or viral outcomes associated with MOR agonists or antagonists (e.g., naltrexone) in HIV-infected PWIDs. The primary objective of this proposal is to establish the extent and pathogenesis of residual immune activation/inflammation, levels of immune reconstitution, and HIV measures in HIV-1-infected PWID who start cART concomitant with medication for opioid use disorder in an addiction clinic with three strategies: a) integrated treatment program (ITP) with oral methadone maintenance, or b) ITP with oral buprenorphine, or c) ITP with extended-release naltrexone.

The primary hypothesis is that PWIDs receiving MOR agonists (i.e. methadone maintenance) will have impaired cART-mediated immune reconstitution outcomes and/or higher levels of systemic immune activation and cell-associated HIV as compared to PWIDs receiving MOR partial agonist (i.e., buprenorphine/naloxone) or antagonist (i.e., extended-release naltrexone).

The investigators will test these hypotheses in the following specific aims:

Specific Aim 1: To define the impact of sustained MOR stimulation on the kinetics and extent of immune reconstitution and activation in HIV-1-infected PWID who are starting cART. To this end, the investigators will compare long-term changes in immune activation and senescence, systemic inflammation, and biological immune reconstitution parameters in a cohort of PWID with chronic HIV infection initiating ART, randomized 1:1:1 to either methadone, buprenorphine/naloxone or extended-release naltrexone.

Specific Aim 2: To define the clinical and virological correlates of long-term treatment with MOR full agonist (methadone), partial agonist (buprenorphine/naloxone) and antagonist (extended-release naltrexone), by analysis of clinical outcomes (CD4 count), adherence to ART, and retention in care. Viral measures will focus on the changes in persistent HIV reservoir measures on ART (i.e., characterization of cell-associated viral RNA and DNA species in PBMC).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
78

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
  • Vietnam
      • Ho Chi Minh City, Vietnam
        • Go Vap Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Meet DSM-5 criteria for moderate to severe opiate use disorder (as determined by DSM-5 checklist)
  • Opiate use with a positive urine drug screen for heroin or other opiates (other than methadone, buprenorphine, buprenorphine/naloxone) at screening visit
  • Documented HIV-1 infection with CD4 less than 350 cells/ μL and VL more than 10,000 copies/mL
  • cART-naïve or or on cART no longer than 3 months if already started
  • Willingness to receive cART or on cART no longer than 3 months if already started
  • Willingness to be randomized to either daily methadone, buprenorphine/naloxone or monthly injection of extended-release naltrexone treatment
  • Ability to understand and complete study procedures
  • Provision of adequate locator information that lists all contact information a participant agrees that the research staff may use to reach him/her
  • All participants must be able to comprehend the purpose of the study and to provide informed consent
  • Is, in the opinion of the study physician, in stable health as determined by pre-study physical examination, medical history, ECG, and laboratory evaluations and is likely to complete the study.
  • Has a total body weight of more than 50 kg (110 pounds) and a body mass index (BMI) of more than 20 at screening.
  • Female subjects: Cannot be pregnant, Cannot be lactating, Must be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal defined as 1 year without bleeding or spotting) OR must agree to use an acceptable method of birth control (e.g., birth control pills, intrauterine device [IUD], or a double barrier method of birth control (condoms and spermicide together; or diaphragm, condom and spermicide together)

Exclusion Criteria:

  • Current cognitive impairment, schizophrenia, paranoid disorder, bipolar disorder not compatible with study procedure (assessed by the medical director of the study)
  • Known neurological, cardiovascular, renal, or other significant medical disorder that is likely to impair or make the individual's participation hazardous Active Tuberculosis or other symptomatic infectious disease AIDS-defining illness
  • Current cancer or other malignancies
  • Advanced liver disease (FibroScan® METAVIR score F3-F4, liver elasticity more than10kPa)
  • Use of immunomodulators
  • Meet DSM-5 criteria for any other substance use disorder (except nicotine)
  • Engagement in opiate medication treatment at baseline (methadone, buprenorphine, buprenorphine/naloxone, naltrexone)
  • Pending legal charges with likely incarceration within next 6 months
  • Currently participating in another clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Methadone
Participants in this arm will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral methadone (MET) and antiretroviral therapy (cART).
Drug: Methadone
Participants will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral methadone syrup (MET), structured counseling sessions (BDRC-based) weekly for the first 3 months and monthly thereafter, and antiretroviral therapy.
Experimental: Buprenorphine/naloxone
Participants in this arm will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral buprenorphine/naloxone and antiretroviral therapy (cART).
Drug: Buprenorphine/naloxone
Participants will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral buprenorphine/naloxone tablets (Suboxone(R)), structured counseling sessions (BDRC-based) weekly for the first 3 months and monthly thereafter, and antiretroviral therapy.
Other Names:
  • Suboxone
Experimental: XR-Naltrexone
Participants in this arm will receive a 48-week integrated treatment program for opiate use disorder with monthly injection extended-release naltrexone (XR-NTX) and antiretroviral therapy (cART).
Drug: XR-Naltrexone
Participants will receive a 48-week integrated treatment program for opiate use disorder with monthly extended-release naltrexone (Vivitrol(R)), structured counseling sessions (BDRC-based) weekly for the first 3 months and monthly thereafter, and antiretroviral therapy.
Other Names:
  • Vivitrol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in sCD14
Time Frame: Baseline, Week-4, -8, -12, -24
Change in plasma sCD14 concentration over 24 weeks
Baseline, Week-4, -8, -12, -24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Marker of Immune Activation: Change in CD38
Time Frame: baseline, Week-4, -8, -12, -24
Change in CD38 concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Immune Activation: HLA-DR
Time Frame: baseline, Week-4, -8, -12, -24
Change in HLA-DR concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Immune Activation: Change in PD1
Time Frame: baseline, Week-4, -8, -12, -24
Change in PD1 expression in C8+ T cells over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Immune Activation: Change in CD169
Time Frame: baseline, Week-4, -8, -12, -24
Change in CD169 expression in monocytes over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Immune Activation: Change in sCD163
Time Frame: baseline, Week-4, -8, -12, -24
Change in plasma sCD163 concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Immune Activation: Change in Type-I IFN
Time Frame: baseline, week -12, -24
Change in type-I IFN signature over 24 weeks
baseline, week -12, -24
Marker of Inflammation: Change in Plasma Hr-CRP
Time Frame: baseline, Week-4, -8, -12, -24
Change in plasma hr-CRP concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Inflammation: Change in D-dimer
Time Frame: baseline, Week-4, -8, -12, -24
Change in plasma d-dimer concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Inflammation: Change in sTNFR-1
Time Frame: baseline, Week-4, -8, -12, -24
Change in plasma sTNFR-1 concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Inflammation: Change in Interleukins IL-6 and IL-10
Time Frame: baseline, Week-4, -8, -12, -24
Change in plasma IL-6 and IL-10 concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Inflammation: Change in TGF-beta
Time Frame: baseline, Week-4, -8, -12, -24
Change in plasma TGF-beta concentration over 24 weeks
baseline, Week-4, -8, -12, -24
Marker of Bacterial Translocation: Change in LPB
Time Frame: Baseline, Week-24
Change in plasma LPB concentration at 24 weeks
Baseline, Week-24
Marker of Bacterial Translocation: Change in LPS
Time Frame: Baseline, Week-24
Change in plasma LPS concentration at 24 weeks
Baseline, Week-24
Marker of Bacterial Translocation: Change in Endo-CAB
Time Frame: Baseline, Week-24
Change in plasma endo-CAB concentration at 24 weeks
Baseline, Week-24
Marker of Bacterial Translocation: Change in Intestinal Fatty Acid-binding Protein (I-FABP)
Time Frame: Baseline, Week-24
Change in plasma I-FABP concentration at 24 weeks
Baseline, Week-24
Marker of Bacterial Translocation: Change in Zonulin-1
Time Frame: Baseline, Week-24
Change in plasma Zonulin-1 concentration at 24 weeks
Baseline, Week-24
Marker of Bacterial Translocation: Change in s16 rDNA
Time Frame: Baseline, Week-24
Change in s16rDNA concentration at 24 weeks
Baseline, Week-24
Marker of Bacterial Translocation: Change in Bacterial Butyryl-coA-coA
Time Frame: Baseline, Week-24
Change in bacterial butyryl-coA-coA concentration at 24 weeks
Baseline, Week-24
Retention in Care
Time Frame: Baseline to Week-24
Number of participants who were receiving treatment ar Week 4, 8, 12, 16, 20 and 24
Baseline to Week-24
HIV-related Outcomes: Change in CD4 Counts
Time Frame: baseline, Week-4, -8, -12, -24
Change in CD4 counts over 24 weeks
baseline, Week-4, -8, -12, -24
HIV-related Outcomes: cART Adherence
Time Frame: baseline, Week-4, -8, -12, -24
Number of participants who get a ART medication at Baseline, Week 4, 8, 12, 24
baseline, Week-4, -8, -12, -24
HIV-related Clinical Outcomes: Viral Load
Time Frame: baseline, Week-12, -24
HIV viral load at Baseline, Week-12, and Week-24
baseline, Week-12, -24
Addiction Clinical Outcomes: Medication for Opioid Use Disorder (MOUD)
Time Frame: Week 24
Comparison of number of participants who completed the treatment in each group
Week 24
Addiction Clinical Outcomes: Change in Drug Use
Time Frame: Baseline, Week-4, -8, -12, -16, -20, -24
Number of participants with opioid use at Baseline, Week-4, 8, 12, 16, 20, and 24
Baseline, Week-4, -8, -12, -16, -20, -24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pennsylvania

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Drug Abuse
The Wistar Institute
Ho Chi Minh City CDC
Institute of Applied Medicine and Epidemiology (IMEA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Luis J Montaner, DVM, D.Phil, The Wistar Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 30, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 1, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 21, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 7, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R01DA048728 (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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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