Clinical trial NCT00270257: Drug Treatment Combined With Drug and Risk Reduction Counseling to Prevent of HIV Infection and Death Among Injection Drug Users
Official title: A Phase III Randomized Controlled Trial to Evaluate the Efficacy of Drug Treatment in Prevention of HIV Infection and Death Among Opiate Dependent Injectors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV Infections
Opioid-Related Disorders
Keywords: HIV Seronegativity
Opiate Addiction
Opiate Dependence
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2005-12-26
Enrollment: 1251
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evidence of HIV-1 Infection or Death for Visits up to 104 Weeks
timeFrame: For visits up to week 104
Secondary outcomes:
measure: Number of Participants With Urinalysis Results Positive for Opiates
timeFrame: Measured through Week 104
measure: Self-report of Continued Injection Opiate Use in the Last 30 Days
timeFrame: Measured through Week 104
measure: Number of Participants Reported Using Injection Equipment (Needles, Syringes, Cookers, Cottons, and Rinse Water) in the Prior 6 Months
timeFrame: Measured through Week 104
measure: Self-reported Number of Injections in the Last Month
timeFrame: Measured through Week 104
measure: Incident Hepatitis C Infections for Thailand and China
timeFrame: Measured through week 156 in Thailand and 104 weeks in China
measure: Incident Hepatitis B Infections
timeFrame: Measured through week 52
Other outcomes:
Locations:
city: Hengzhou Town
country: China
facility: Heng County Ctr. for Disease Control & Prevention CRS
state: Guangxi
city: Nanning
country: China
facility: Guangxi Ctrs. for Disease Control & Prevention and for HIV/AIDS Prevention & Control CRS
state: Guangxi
city: Urumqi
country: China
facility: Xinjiang CRS
state: Xinjiang
city: Chiang Mai
country: Thailand
facility: CMU HIV Prevention CRS
Study officials:
affiliation: Center for Studies of Addiction, University of Pennsylvania
name: David Metzger, PhD
role: STUDY_CHAIR
References:
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citation: Lucas GM, Beauchamp G, Aramrattana A, Shao Y, Liu W, Fu L, Jackson JB, Celentano DD, Richardson P, Metzger D; HPTN 058 study group. Short-term safety of buprenorphine/naloxone in HIV-seronegative opioid-dependent Chinese and Thai drug injectors enrolled in HIV Prevention Trials Network 058. Int J Drug Policy. 2012 Mar;23(2):162-5. doi: 10.1016/j.drugpo.2011.06.005. Epub 2011 Aug 17.
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