Medications for Opioid Use Disorder in HIV

(AMOHI-1 Trial)

Recruiting at 1 trial location

Overseen By Cecile M Denis, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must be taking: Methadone, Buprenorphine/naloxone, Naltrexone

Must not be taking: Immunomodulators

Disqualifiers: Cognitive impairment, Schizophrenia, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

225 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must not be engaged in opiate medication treatment at the start of the trial. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of this drug for opioid use disorder in people with HIV?

Research shows that buprenorphine/naloxone can help integrate opioid dependence and HIV treatment, improving the quality of life for patients. Additionally, extended-release naltrexone has been shown to improve viral suppression in people with HIV and opioid use disorder. ^{1 2 3 4 5}

Is the treatment for opioid use disorder in HIV patients safe?

There are concerns about liver safety and drug interactions with buprenorphine/naloxone in HIV patients, but no specific safety data is provided for the other treatments. ^{1 2 4 6 7}

How does the drug treatment for opioid use disorder in HIV differ from other treatments?

This treatment is unique because it combines medications like buprenorphine/naloxone, methadone, and extended-release naltrexone, which not only help manage opioid addiction but also improve HIV treatment outcomes by integrating care for both conditions. These medications can enhance viral suppression and retention in HIV treatment, offering a comprehensive approach compared to standard treatments that may not address both issues simultaneously. ^{1 2 8 9 10}

Research Team

Luis J Montaner, DVM, D.Phil

Principal Investigator

The Wistar Institute

Eligibility Criteria

This trial is for adults with HIV and moderate to severe opioid use disorder who haven't started or have just begun antiretroviral therapy. They must be in stable health, not pregnant or breastfeeding, able to consent, and willing to take methadone, buprenorphine/naloxone, or extended-release naltrexone.

Inclusion Criteria

I have either not started cART or have been on it for no more than 3 months.

Ability to understand and complete study procedures

I am willing to start or have started combination antiretroviral therapy (cART) within the last 3 months.

Exclusion Criteria

I do not have any major health issues that could make participating dangerous for me.

Current cognitive impairment, schizophrenia, paranoid disorder, bipolar disorder not compatible with study procedure (assessed by the medical director of the study)

I do not have active tuberculosis or any AIDS-related illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 48-week integrated treatment program for opiate use disorder with either methadone, buprenorphine/naloxone, or extended-release naltrexone, along with antiretroviral therapy (cART)

48 weeks

Weekly visits for medication administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Buprenorphine/naloxone
• Methadone
• XR-Naltrexone

Trial Overview The study tests how long-term treatments for opioid use disorder (methadone, buprenorphine/naloxone, XR-naltrexone) affect immune system recovery in people with HIV starting antiretroviral therapy.

Participant Groups

Group I: XR-Naltrexone Experimental Treatment 1 Intervention

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).

Group II: Methadone Experimental Treatment 1 Intervention

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).

Group III: Buprenorphine/naloxone Experimental Treatment 1 Intervention

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).

Buprenorphine/naloxone is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Suboxone for:

• Opioid dependence
• Opioid use disorder

Approved in United States as Suboxone for:

• Opioid dependence
• Opioid use disorder

Approved in Canada as Suboxone for:

• Opioid dependence
• Opioid use disorder

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

IMEA Paris

Collaborator

Trials

1

Recruited

230+

Ho Chi Minh City CDC

Collaborator

Trials

1

Recruited

230+

National Institute of Drug Abuse

Collaborator

Trials

11

Recruited

12,500+

The Wistar Institute

Collaborator

Trials

10

Recruited

790+

Institute of Applied Medicine and Epidemiology (IMEA)

Collaborator

Trials

1

Recruited

230+

Ho Chi Minh City CDC

Collaborator

Trials

1

Recruited

230+

Findings from Research

In a study of 303 HIV-infected opioid-dependent patients, buprenorphine/naloxone treatment led to a significant reduction in illicit opioid use, decreasing from 84% at baseline to 42% over one year for those who remained in treatment.

Retention in buprenorphine/naloxone treatment declined over the year, with 74% of patients retained in the first quarter and only 49% by the fourth quarter, highlighting the need for improved strategies to maintain treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment outcomes among HIV-infected opioid-dependent patients receiving buprenorphine/naloxone. Fiellin, DA., Weiss, L., Botsko, M., et al.[2021]

In a 48-week study involving 200 participants with opioid addiction and HIV, the naltrexone implant group showed a significant improvement in maintaining viral loads below 400 copies per mL at 48 weeks compared to the oral naltrexone group, suggesting that long-acting naltrexone may enhance HIV treatment outcomes.

Despite some serious adverse events, including deaths in both groups, the study indicates that longer opioid blockade from the implant may help protect against missed antiretroviral therapy doses and impulsive behaviors that could lead to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial. Krupitsky, E., Blokhina, E., Zvartau, E., et al.[2020]

In a study involving 93 prisoners with HIV and opioid use disorder, those receiving extended-release naltrexone (XR-NTX) showed a significant improvement in maintaining viral suppression (VS) from 37.9% at baseline to 60.6% at 6 months, compared to no improvement in the placebo group.

While the overall difference in VS levels at 6 months between XR-NTX and placebo was not statistically significant, XR-NTX was associated with a higher likelihood of improving or maintaining VS, indicating its potential effectiveness in supporting health outcomes for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial. Springer, SA., Di Paola, A., Azar, MM., et al.[2020]

In a study involving 570 adults with opioid use disorder, buprenorphine-naloxone was found to be more cost-effective than extended-release naltrexone, being preferred in 97% of cases at 24 weeks and 85% at 36 weeks based on quality-adjusted life-years (QALYs).

The analysis suggests that buprenorphine-naloxone is the better first-line treatment option, especially for patients needing detoxification before starting extended-release naltrexone, although the study had limitations such as a relatively short follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. Murphy, SM., McCollister, KE., Leff, JA., et al.[2020]

In a study of 289 HIV-infected individuals with opioid dependence, those receiving clinic-based buprenorphine/naloxone (bup/nx) showed significant improvements in mental health-related quality of life (HRQOL) over 12 months, with scores increasing from 38.3 to 43.4.

While mental HRQOL improved, physical HRQOL remained unchanged; however, continued bup/nx treatment was associated with positive trends in both physical and mental HRQOL, suggesting that this therapy can help mitigate some negative impacts of opioid dependence in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved quality of life for opioid-dependent patients receiving buprenorphine treatment in HIV clinics. Korthuis, PT., Tozzi, MJ., Nandi, V., et al.[2023]

In a study of 303 opioid-dependent HIV-infected patients, buprenorphine/naloxone treatment did not result in significant changes in liver enzymes (AST and ALT), indicating no measurable hepatic toxicity over time.

The study found no pharmacodynamic interactions between buprenorphine/naloxone and the antiretroviral drug atazanavir, suggesting that buprenorphine/naloxone is safe to use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients. Vergara-Rodriguez, P., Tozzi, MJ., Botsko, M., et al.[2020]

In a 12-week pilot study involving 16 HIV-positive, opioid-dependent patients, integrating buprenorphine/naloxone into HIV care showed high treatment retention, with 81% completing the study and significant reductions in opioid use, as evidenced by urine tests.

Patients also experienced improvements in HIV-related health markers, with a significant decline in HIV-1 RNA levels, indicating that buprenorphine treatment is not only feasible but also beneficial for managing both opioid dependence and HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of integrated buprenorphine/naloxone and HIV clinical care. Sullivan, LE., Barry, D., Moore, BA., et al.[2013]

Methadone and buprenorphine significantly enhance HIV treatment outcomes by improving viral suppression, adherence to antiretroviral therapy, and reducing overall mortality in individuals with opioid use disorder (OUD).

Extended-release naltrexone has shown effectiveness in improving HIV viral suppression, particularly for individuals with HIV transitioning from incarceration, highlighting the importance of integrating medications for opioid use disorder with HIV treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medications for Treatment of Opioid Use Disorder among Persons Living with HIV. Fanucchi, L., Springer, SA., Korthuis, PT.[2020]

HIV-infected individuals experience higher rates of chronic pain and are more likely to be prescribed and use higher doses of opioids, which increases their risk for developing opioid use disorder.

Buprenorphine treatment for opioid use disorder has been shown to improve HIV-related outcomes, suggesting it may be an effective management strategy for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioids and HIV Infection: From Pain Management to Addiction Treatment. Cunningham, CO.[2018]

In a trial involving 114 participants with untreated HIV and opioid use disorder, extended-release naltrexone (XR-NTX) showed similar rates of HIV viral suppression compared to standard treatment with buprenorphine or methadone, but it could not be conclusively proven to be non-inferior.

Participants who started XR-NTX reported fewer days of opioid use in the past 30 days compared to those receiving standard treatment, suggesting that XR-NTX may help reduce opioid use among those who initiate the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV clinic-based extended-release naltrexone versus treatment as usual for people with HIV and opioid use disorder: a non-blinded, randomized non-inferiority trial. Korthuis, PT., Cook, RR., Lum, PJ., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Drug treatment outcomes among HIV-infected opioid-dependent patients receiving buprenorphine/naloxone. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Improved quality of life for opioid-dependent patients receiving buprenorphine treatment in HIV clinics. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

A trial of integrated buprenorphine/naloxone and HIV clinical care. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Medications for Treatment of Opioid Use Disorder among Persons Living with HIV. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Opioids and HIV Infection: From Pain Management to Addiction Treatment. [2018]

10. England pubmed.ncbi.nlm.nih.gov

HIV clinic-based extended-release naltrexone versus treatment as usual for people with HIV and opioid use disorder: a non-blinded, randomized non-inferiority trial. [2023]