Adherence to HIV Therapy in Heroin Addicts: Oral vs XR-NTX
Condition: HIV; Substance Abuse; HIV Infections
MeSH terms: Substance-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      Substance use, particularly the compulsive behaviors associated with addiction, lead to
      unhealthy behaviors including non-adherence to antiretroviral therapy (ART) and treatment
      failure. High on the list of disorders leading to non-adherence is heroin addiction as a wide
      range of impulsive, high-risk behaviors accompanies it. The science of adherence would be
      improved by developing new methods to prevent relapse to heroin addiction, especially methods
      that can be used in settings that are not limited by the aims to test such a method using an
      implantable naltrexone formulation (IN) that is approved in Russia and blocks opioid effects
      for 3 months. The efficacy of the IN should be better than oral naltrexone (ON) because it
      does not depend on daily behavior to take a tablet and maintains a constant plasma level for
      months, which should result in sustained blockade, less relapse, and better ART adherence and
      treatment response.
    

Detailed description: 
      This is a double blind, double-dummy, placebo controlled, randomized trial of a 48-week
      course of implant naltrexone vs. oral naltrexone, each arm with drug counseling every two
      weeks, for 200 HIV+ patients who are in early remission from opioid dependence, and who are
      interested in relapse prevention treatment medication, and starting their first episode of
      antiretroviral therapy at the Botkin Infectious Disease Hospital in St. Petersburg or the
      Leningrad Regional AIDS Center. Early remission was chosen because relapse risk is the
      highest at this point, thus maximizing the chances for detecting a naltrexone effect. The
      first antiretroviral therapy treatment episode was chosen because it is feasible (relatively
      few opioid addicted Russians have been treated with antiretroviral therapy), and because the
      virus is less likely to have developed secondary resistance.

      Participants will be recruited from the AIDS and addiction programs and who meet study
      admission criteria will be stratified within each site according to baseline viral load
      (>100,000 copies/<100,000 copies) and cluster of differentiation 4 (CD4) count (>50/<50
      copies). Participants will be randomized to a treatment condition, receive a naloxone
      challenge, and if pass be prescribed oral naltrexone or oral placebo and implant/implant
      placebo), and given a schedule for addiction counseling and HIV treatment appointments. A
      2-week supply of oral medication will be provided at each bi-weekly counseling session, and
      will be re-implanted at weeks 12, 24, and 36. Only the research pharmacist will know the
      group assignments, however the blind can be broken in case of emergency.

      The primary outcome measure will be to compare implanted naltrexone versus oral naltrexone on
      ability to achieve a viral load of <400 copies at weeks 24 and 48.

      Secondary outcomes are to compare the efficacy of the two addiction treatments; to study the
      adherence to antiretroviral therapy; to evaluate time to relapse and the number of days to
      relapsed; to evaluate decline in CD4 counts; to evaluate HIV risk behavior; to evaluate
      opioid positive urine tests; and to evaluate the number of days that patients will keep their
      scheduled appointments. The Investigator will also monitor psychiatric symptoms, other drug
      use, and overall adjustment.
    

Intervention name(s): Oral Naltrexone; Naltrexone Implant; Group Drug Counseling Manual Driven
Intervention type(s): Drug; Drug; Behavioral
Intervention description(s): 50 mg/day-oral; monthly-implant; Given to both groups biweekly, weeks 2 - 48. Counseling will consist of three components: 1) giving advice, support and clinical management aimed to maintain abstinence; 2) adherence enhancement to encourage keeping appointments, taking ART medications as prescribed and getting treatment for associated problems; and 3) reviewing behaviors that are likely to spread HIV and other infectious diseases, and counseling on how to stop them.
Other intervention name(s): Revia; Prodetoxon
Intervention MeSH terms: Naltrexone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Viral Loads; Naltrexone; HIV Risk; Substance Abuse