Directly Administered HIV Therapy in Methadone Clinics

Study Overview
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Brief Summary
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The purpose of this study is to determine whether providing directly administered antiretroviral therapy to HIV-infected who receive methadone therapy leads to better treatment outcomes than if they take HIV medications on their own.

Detailed Description
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We propose to conduct a randomized, unblinded, clinical trial of a medication adherence intervention in opioid-dependent, HIV-infected participants who are initiating new antiretroviral therapy, and who receive opioid agonist maintenance therapy with methadone or buprenorphine in opioid treatment programs (OTPs) in Baltimore, MD. Randomization will be stratified by study site and prior antiretroviral exposure. Two hundred participants will be randomly assigned 1:1 self-administered antiretroviral therapy (SAT) or directly administered antiretroviral therapy (DAART). Subjects assigned to DAART will take morning doses of antiretroviral therapy with a nurse or medical assistant in a private room at the OTP. DAART subjects will be transferred to self-administered therapy after 12 months. This is a 5 year study and participants will be enrolled between month 6 and month 42 of the study. The maximum follow-up for individual participants will be 18 months. Based on our pilot experience we anticipate 50% of subjects will be women, 80% African American, with a median age of 44 years. The following outcomes will be compared in the two study arms: Suppression of the viral load (primary outcome) Changes in CD4+ cell counts The development of antiretroviral drug resistance Retention to opioid agonist maintenance therapy, urine toxicology screens for drugs of abuse, and self-reported drug and alcohol use Self-reported adherence with therapy, retention to ART, and clinical and psychosocial moderators of adherence Electronically monitored medication adherence, using MEMS caps, in the first 2 months of the study Outcomes data will be obtained at study assessment visits at baseline, 3 months, 6 months, 12 months, and 18 months. Participants will provide contact information, take an interviewer-administered survey, and provide blood and urine samples at study assessment visits. MEMS cap data will be captured at 1 month and 2 months. Subjects will be compensated for successful completion of study assessment visits and MEMS interrogations.

Official Title
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Directly Administered vs. Self-administered Antiretroviral Therapy in Methadone Clinics

Conditions
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HIV Infections, Heroin Dependence

Intervention / Treatment
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* Behavioral: Directly administered antiretroviral therapy (DAART)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen years of age or older Documented serologic evidence of HIV infection (positive ELISA and Western blot) Identifiable medical provider, who is responsible for managing HIV treatment Proof that ART has been prescribed and that patient has prescription medication coverage Nadir CD4+ cell count < 350/mm3 or off-treatment HIV RNA > 55,000 copies/ml if asymptomatic and ART naive Current plasma HIV RNA > 500 copies/ml Initiating ART for first time, reinitiating therapy after stopping, or changing therapy due to virologic failure ART with at least 3 agents, including a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, or abacavir Methadone or buprenorphine maintenance therapy > 3 weeks, with no planned detoxification Exclusion Criteria: Need to use ART dosed more frequently than twice daily, Need to use a liquid preparation of antiretroviral medication, Documented triple-class antiretroviral resistance (defined below), Participation in another study or program that includes directly observed therapy. Use of ART regimens that are expressly discouraged in DHHS HIV clinical care guidelines Triple-class antiretroviral resistance will be defined according to IAS-USA interpretive guidelines: NRTI class - 3 thymidine or non-thymidine-associated mutations (excluding the M184V mutation) or a multi-nucleoside resistance mutation in reverse transcriptase; PI class - 3 protease mutations, including 1 primary mutation; NNRTI class - 1 primary (K103N or Y188L) or 2 secondary NNRTI-associated mutations in reverse transcriptase.

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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Behavioral: Directly administered antiretroviral therapy (DAART)<br>* Participants are observed taking HIV medications on days when they receive opioid agonist therapy.<br>|
| No Intervention: B<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV RNA < 50 c/mL |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log10 change in HIV RNA from baseline |  | 12 months | 
| HIV RNA < 50 c/mL 6 mos. after intervention |  | 18 months | 
| Log10 change in HIV RNA from baseline 6 months post intervention |  | 18 months | 
| Change in CD4 cell count from baseline |  | 18 months | 
| ART utilization |  | 12 months | 
| Development of antiretroviral resistance |  | 12 months | 
| Retention to substance abuse treatment |  | 12 months | 
| Urine drug screen positivity in follow-up |  | 12 months | 
| Electronically monitored adherence |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Antiretroviral therapy, Heroin dependence, Methadone, Buprenorphine