Drug Treatment Combined With Drug and Risk Reduction Counseling to Prevent of HIV Infection and Death Among Injection Drug Users

Study Overview
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Brief Summary
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Drug abuse and HIV/AIDS are serious global health problems. Injection drug use is currently the major mode of transmission of HIV in many countries. The purpose of this study is to determine the effectiveness of drug and risk reduction counseling combined with either substitution drug treatment with buprenorphine/naloxone (BUP/NX) or short-term detoxification with BUP/NX in preventing HIV transmission among injection drug users. Participants will be recruited for this study in China and Thailand.

Detailed Description
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Effective HIV prevention among injection drug users (IDUs) requires educating the at-risk population about HIV transmission and risky behavior, and providing the means for behavior change. Current treatment for opiate dependence focuses on reducing the frequency of drug use. BUP/NX is a combination pill currently used to treat opiate-dependent individuals. This trial will evaluate the effectiveness of two therapies in preventing HIV transmission among IDUs. Drug and risk reduction counseling combined with either long term medication assisted treatment (LT-MAT) with BUP/NX or short term medication assisted treatment (ST-MAT) with BUP/NX will be compared in preventing the transmission of HIV among opiate-dependent individuals. This study will last 4.5 years. Participants in this study will be randomly assigned to one of two treatment arms. Group 1 will receive LT-MAT with BUP/NX. Group 2 will receive ST-MAT with BUP/NX. An initial 4-week safety and feasibility phase will involve the first 50 participants at each site and will last approximately 30 weeks. Study visits will occur every week and will include a physical exam and blood and urine collection. The main treatment phase of the study will last 52 weeks. Participants in Group 1 will receive BUP/NX under the tongue, at first daily and then three times a week for 52 weeks. Participants assigned to Group 1 will take part in a BUP/NX reduction phase, which will occur between Weeks 47 and 52. Participants in Group 2 will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator. Participants assigned to Group 2 will receive BUP/NX for a maximum of 18 days; detoxification may be repeated at Week 26 if the participant is still injecting opiates. After Week 4 of the safety phase and Weeks 26 and 52 of the overall study, participants will complete an intervention acceptability assessment. In addition, participants in both groups will attend drug and risk reduction counseling weekly. After the first 12 weeks, participants will return every 4 weeks for 10 more counseling sessions. HIV testing, hepatitis C testing, risk assessment, and urine tests for opiates will occur at screening and at Weeks 26, 52, 78, 104, 130 and 156. Plasma from blood samples will be stored at each of these visits. Hepatitis B testing will occur at Week 26. Participants in China will attend study visits through approximately Week 104, and participants in Thailand will attend study visits through approximately Week 156. Participants in China who have been incarcerated may participate in an optional substudy, which is examining the withdrawal effects from BUP/NX after incarceration. Participants who agree to take part in the substudy will attend one study visit and will complete a questionnaire.

Official Title
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A Phase III Randomized Controlled Trial to Evaluate the Efficacy of Drug Treatment in Prevention of HIV Infection and Death Among Opiate Dependent Injectors

Conditions
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HIV Infections, Opioid-Related Disorders

Intervention / Treatment
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* Drug: Buprenorphine/Naloxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-uninfected within 28 days of enrollment Meets DSM-IV criteria for opiate dependence Positive urine test for opiates Injected opiates at least 12 times in the 28 days prior to enrollment, according to self-report Willing to use acceptable forms of contraception for the first 12 months of the study Able to provide contact information and willing to be contacted by study staff as necessary Available for study visits for at least 2 years Exclusion Criteria: Current treatment with methadone, morphine, levo-alpha-acetyl-methadol (LAAM), naltrexone, or nalmefene Currently enrolled in another HIV prevention or drug use intervention study Known sensitivity to buprenorphine or naloxone Requires immediate medical attention for dependence on alcohol, benzodiazepines, or other substances. People who are dependent on tobacco are not excluded. Currently injecting drugs of abuse other than opiates, more than twice in the last 28 days, according to self-report Psychological disturbance or cognitive impairment that may interfere with the study Acute or chronic kidney failure Certain abnormal laboratory values Any other medical or psychiatric condition that, in the opinion of the investigator, would make participation in this study unsafe Pregnant or breastfeeding Inclusion Criteria for Substudy: Current or former participant in HPTN 058 study in Xinjiang who was actively in the long-term treatment arm on stable maintenance dose of Suboxone when detained/arrested (last dose within 2 days of incarceration), resulting in immediate cessation of Suboxone without tapering Currently released from detention Willing to complete one-time questionnaire Willing to sign informed consent Exclusion Criteria for Substudy: Any medical or psychiatric condition that, in the opinion of the investigator, would make participation in the study unsafe, or would otherwise interfere with the study objectives or interpretation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Long term medication assisted treatment (LT-MAT)<br>Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52 | Drug: Buprenorphine/Naloxone<br>* Oral tablet<br>* Other names: BUP/NX;|
| Experimental: Short term medication assisted treatment (ST-MAT)<br>Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52. | Drug: Buprenorphine/Naloxone<br>* Oral tablet<br>* Other names: BUP/NX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of HIV-1 Infection or Death for Visits up to 104 Weeks | The primary endpoint for the study was cumulative HIV infection or death after a second year of follow-up (i.e. at week 104), one year after completion of the treatment phase, designed to test a durable intervention effect. | For visits up to week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Urinalysis Results Positive for Opiates | Urine drug screen were assessed monthly and semiannually. | Measured through Week 104 | 
| Self-report of Continued Injection Opiate Use in the Last 30 Days | All participants completed interviewer-administered assessments of injection and non-injection drug use at baseline and at semi-annual visits. | Measured through Week 104 | 
| Number of Participants Reported Using Injection Equipment (Needles, Syringes, Cookers, Cottons, and Rinse Water) in the Prior 6 Months |  | Measured through Week 104 | 
| Self-reported Number of Injections in the Last Month |  | Measured through Week 104 | 
| Incident Hepatitis C Infections for Thailand and China | HCV antibody using two different HCV EIA assays (Ortho HCV antibody version 3.0 and Wantai HCV antibody assay) at baseline and between 26-156 weeks later. If both HCV EIA antibody assays were nonreactive, then the participant was considered not to be HCV infected. If either assay was reactive, then the Ortho HCV assay was repeated in duplicate. If two of 3 Ortho HCV assays were reactive, then the participant was considered to be HCV infected. Samples that were repeatedly reactive for HCV antibody at a follow-up visit were tested for HCV RNA by the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV assay. Not all participants had follow-up testing performed in China due to early closure of the study by the Data Safety Monitoring Board on account of futility due to a low HIV incidence (the primary study endpoint). Analysis was done separately for both countries | Measured through week 156 in Thailand and 104 weeks in China | 
| Incident Hepatitis B Infections | Serum samples were tested at baseline and between 26-52 weeks later for Hepatitis B surface antigen (HBsAg) using a commercial enzyme immunoassay (EIA) (Abbott Murex HBsAg version 3.0). If the HBsAg test was initially non-reactive, then the participant was considered to be negative for HBsAg. If the HBsAg test was initially reactive, then it was repeated in duplicate. If at least two of 3 tests were reactive, then the participant was considered to be positive for HBsAg. | Measured through week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Seronegativity, Opiate Addiction, Opiate Dependence