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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how different medications for opioid use disorder, such as methadone, buprenorphine/naloxone (also known as Suboxone, Zubsolv, or Bunavail), and extended-release naltrexone (also known as Vivitrol), affect the immune system in people with both HIV and an opioid addiction. It focuses on individuals starting antiretroviral therapy to manage their HIV. To qualify, participants must have tested positive for HIV and heroin or other opioids and must not have been on HIV treatment for more than three months. This trial could suit individuals dealing with both HIV and opioid use who are ready to begin a treatment plan. As a Phase 2 trial, it measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have commonly used buprenorphine/naloxone to treat opioid use disorder, testing it in over 3,000 people and providing extensive safety information. However, some individuals have experienced serious breathing problems with its use. Methadone, another treatment for opioid use disorder, has been shown to help reduce risky behaviors, suggesting it is generally well-tolerated, though individual reactions can vary. Extended-release naltrexone (XR-Naltrexone) is considered a safe option for people with opioid use disorder, including those with HIV. Although usually well-tolerated, some serious side effects, such as severe injection site reactions, have been reported. Overall, while these treatments have been shown to be safe for many, it is important to consider personal health conditions and discuss options with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they integrate opioid use disorder (OUD) treatment with antiretroviral therapy for HIV, offering a comprehensive approach. Buprenorphine/naloxone and methadone are known for their effectiveness in reducing opioid cravings and withdrawal symptoms, but the integration with daily observed doses aims to enhance adherence and outcomes. Meanwhile, XR-Naltrexone offers a unique advantage with its monthly injection, potentially improving compliance for those who struggle with daily medication. This trial aims to optimize treatment for individuals dealing with the dual challenges of OUD and HIV, providing a more holistic and potentially more effective solution.

What evidence suggests that this trial's treatments could be effective for opioid use disorder in HIV?

Research has shown that buprenorphine/naloxone, which participants in this trial may receive, reduces opioid use and improves HIV treatment outcomes when used in HIV clinics. It also lowers overdose risk and increases survival rates. Methadone, another treatment option in this trial, provides similar benefits, including longer treatment retention, reduced opioid use, and better HIV control. Extended-release naltrexone (XR-NTX), also under study in this trial, reduces opioid use and improves HIV outcomes, with fewer relapses compared to other treatments. All three medications effectively treat opioid use disorder and can enhance HIV treatment when combined with antiretroviral therapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Luis J Montaner, DVM, D.Phil

Principal Investigator

The Wistar Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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]

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8082651/

HIV clinic-based buprenorphine plus naloxone versus referral ... Like methadone, systematic reviews demonstrate that buprenorphine, a partial opioid agonist, is effective for treatment of OUD, reduces HIV transmission, and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3863630/

Drug Treatment Outcomes among HIV-Infected Opioid ... Buprenorphine/naloxone provided in HIV treatment settings can decrease opioid use. Strategies are needed to improve retention and address ongoing drug use.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871614007820

The impact of buprenorphine/naloxone treatment on HIV ... Recent data demonstrate the impact of integrated buprenorphine/naloxone and HIV treatment on improving HIV and drug treatment outcomes (Altice et al., 2011, ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2760032

Comparative Effectiveness of Different Treatment Pathways ... Treatment with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with other treatments.

5. cdc.gov cdc.gov/mmwr/volumes/73/wr/mm7325a1.htm

Treatment for Opioid Use Disorder: Population Estimates Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/020733s031s032lbl.pdf

This label may not be the latest approved by FDA. For current ... In total, safety data were available from 3214 opioid-dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction.

7. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=072b2c2e-a564-4bb4-8954-9349a7923807

Label: BUPRENORPHINE AND NALOXONE tablet - DailyMed Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of the potential ...

8. webmd.com webmd.com/drugs/2/drug-64740-1356/buprenorphine-naloxone-sublingual/buprenorphine-naloxone-film-sublingual/details

Buprenorphine/Naloxone (Suboxone, Bunavail, and others) Buprenorphine/naloxone is commonly used to treat opioid use disorder. It can help you no longer feel the need to use opioids.

9. ec.europa.eu ec.europa.eu/health/documents/community-register/2017/20171110139126/anx_139126_en.pdf

Zubsolv, INN-buprenorphine/naloxone There are no adequate data from the use of buprenorphine/naloxone in pregnant women. ... Efficacy and safety data for buprenorphine/naloxone are primarily derived ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/204242s031lbl.pdf

Reference ID: 5593165 - accessdata.fda.gov In total, safety data were available for 538 opioid-dependent subjects exposed to ZUBSOLV. (buprenorphine/naloxone) sublingual tablets when used for initial ...