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Opioid-use DisorderPhase 2AMOHI-1NCT04480554

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

A Phase 2 study testing Methadone, Buprenorphine/naloxone and XR-Naltrexone in people with Opioid-use Disorder and HIV-1-infection, run by University of Pennsylvania at 2 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Methadone, Buprenorphine/naloxone and XR-Naltrexone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
2 sitesin 2 countries
Study dates
30 Jan 2023to 30 Jun 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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)

Who cannot join

  • 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)
Show all 9Show fewer
  • 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

Vietnam1 site

  • Go Vap Clinic

    Ho Chi Minh City

Other trials in Vietnam

About this study

Official title: 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.

Read the 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).

Being tested
Methadone, Buprenorphine/naloxone, XR-Naltrexone
Keywords
Opioid use disorder, HIV, Medication for Opioid Use Disorder, Antiretroviral therapy, Immune activation
Medical subject headings
Opioid-Related Disorders, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethadoneDrug

    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.

  • Buprenorphine/naloxoneDrug

    Also called Suboxone

    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.

  • XR-NaltrexoneDrug

    Also called Vivitrol

    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.

Study groups in NCT04480554
Study groupRoleWhat they receive
MethadoneExperimentalParticipants 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).
Receives: Drug: Methadone
Buprenorphine/naloxoneExperimentalParticipants 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).
Receives: Drug: Buprenorphine/naloxone
XR-NaltrexoneExperimentalParticipants 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).
Receives: Drug: XR-Naltrexone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in sCD14

    Change in plasma sCD14 concentration over 24 weeks

    Measured: Baseline, Week-4, -8, -12, -24

Secondary outcomes (24)

  1. Marker of Immune Activation: Change in CD38

    Change in CD38 concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  2. Marker of Immune Activation: HLA-DR

    Change in HLA-DR concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  3. Marker of Immune Activation: Change in PD1

    Change in PD1 expression in C8+ T cells over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  4. Marker of Immune Activation: Change in CD169

    Change in CD169 expression in monocytes over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  5. Marker of Immune Activation: Change in sCD163

    Change in plasma sCD163 concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  6. Marker of Immune Activation: Change in Type-I IFN

    Change in type-I IFN signature over 24 weeks

    Measured: baseline, week -12, -24

  7. Marker of Inflammation: Change in Plasma Hr-CRP

    Change in plasma hr-CRP concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  8. Marker of Inflammation: Change in D-dimer

    Change in plasma d-dimer concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  9. Marker of Inflammation: Change in sTNFR-1

    Change in plasma sTNFR-1 concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  10. Marker of Inflammation: Change in Interleukins IL-6 and IL-10

    Change in plasma IL-6 and IL-10 concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  11. Marker of Inflammation: Change in TGF-beta

    Change in plasma TGF-beta concentration over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  12. Marker of Bacterial Translocation: Change in LPB

    Change in plasma LPB concentration at 24 weeks

    Measured: Baseline, Week-24

  13. Marker of Bacterial Translocation: Change in LPS

    Change in plasma LPS concentration at 24 weeks

    Measured: Baseline, Week-24

  14. Marker of Bacterial Translocation: Change in Endo-CAB

    Change in plasma endo-CAB concentration at 24 weeks

    Measured: Baseline, Week-24

  15. Marker of Bacterial Translocation: Change in Intestinal Fatty Acid-binding Protein (I-FABP)

    Change in plasma I-FABP concentration at 24 weeks

    Measured: Baseline, Week-24

  16. Marker of Bacterial Translocation: Change in Zonulin-1

    Change in plasma Zonulin-1 concentration at 24 weeks

    Measured: Baseline, Week-24

  17. Marker of Bacterial Translocation: Change in s16 rDNA

    Change in s16rDNA concentration at 24 weeks

    Measured: Baseline, Week-24

  18. Marker of Bacterial Translocation: Change in Bacterial Butyryl-coA-coA

    Change in bacterial butyryl-coA-coA concentration at 24 weeks

    Measured: Baseline, Week-24

  19. Retention in Care

    Number of participants who were receiving treatment ar Week 4, 8, 12, 16, 20 and 24

    Measured: Baseline to Week-24

  20. HIV-related Outcomes: Change in CD4 Counts

    Change in CD4 counts over 24 weeks

    Measured: baseline, Week-4, -8, -12, -24

  21. HIV-related Outcomes: cART Adherence

    Number of participants who get a ART medication at Baseline, Week 4, 8, 12, 24

    Measured: baseline, Week-4, -8, -12, -24

  22. HIV-related Clinical Outcomes: Viral Load

    HIV viral load at Baseline, Week-12, and Week-24

    Measured: baseline, Week-12, -24

  23. Addiction Clinical Outcomes: Medication for Opioid Use Disorder (MOUD)

    Comparison of number of participants who completed the treatment in each group

    Measured: Week 24

  24. Addiction Clinical Outcomes: Change in Drug Use

    Number of participants with opioid use at Baseline, Week-4, 8, 12, 16, 20, and 24

    Measured: Baseline, Week-4, -8, -12, -16, -20, -24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2020
  2. Study start30 Jan 2023
  3. Primary completion30 Jun 2025
  4. Study completion30 Jun 2025

Why it stopped: Funding not renewed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study will enroll 225 HIV-positive subjects who meet DSM-5 opiate use disorder criteria and who are using opiates (primarily heroin). All subjects will receive a 48-week integrated treatment program for opiate use disorder with either (randomly assigned) daily directly observed oral methadone (MET) and buprenorphine/naloxone (BUP/NX) or monthly injection extended-release naltrexone (XR-NTX).
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04480554
Sponsor's protocol ID
R01DA048728
Acronym
AMOHI-1
Status last verified
Mar 2026
First submitted
1 Jul 2020
Last updated
7 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Methadone, Buprenorphine/naloxone and XR-Naltrexone in people with Opioid-use Disorder and HIV-1-infection, run by University of Pennsylvania at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in sCD14 (time frame: Baseline, Week-4, -8, -12, -24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04480554.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.

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