Directly Administered HIV Therapy in Methadone Clinics

Condition(s) targeted: HIV Infections; Heroin Dependence

Intervention: Directly administered antiretroviral therapy (DAART) (Behavioral); Self-administered therapy (SAT) (Behavioral)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Johns Hopkins University

Official(s) and/or principal investigator(s):
Gregory M. Lucas, MD, PhD, Principal Investigator, Affiliation: Johns Hopkins University

Overall contact:
B. Anna Mullen, RN, Phone: 410-502-5088, Email: bmullen1@jhmi.edu

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.

Official title: Directly Administered vs. Self-Administered Antiretroviral Therapy in Methadone Clinics

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: HIV RNA < 50 c/mL

Secondary outcome:

Log10 change in HIV RNA from baseline

HIV RNA < 50 c/mL 6 mos. after intervention

Log10 change in HIV RNA from baseline 6 months post intervention

Change in CD4 cell count from baseline

ART utilization

Development of antiretroviral resistance

Retention to substance abuse treatment

Urine drug screen positivity in follow-up

Electronically monitored adherence

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Eighteen years of age or older

2. Documented serologic evidence of HIV infection (positive ELISA and Western blot)

3. Identifiable medical provider, who is responsible for managing HIV treatment

4. Proof that ART has been prescribed and that patient has prescription medication coverage

5. Nadir CD4+ cell count < 350/mm3 or off-treatment HIV RNA > 55,000 copies/ml if asymptomatic and ART naive

6. Current plasma HIV RNA > 500 copies/ml

7. Initiating ART for first time, reinitiating therapy after stopping, or changing therapy due to virologic failure

8. ART with at least 3 agents, including a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, or abacavir

9. Methadone or buprenorphine maintenance therapy > 3 weeks, with no planned detoxification

Exclusion Criteria:

1. Need to use ART dosed more frequently than twice daily,

2. Need to use a liquid preparation of antiretroviral medication,

3. Documented triple-class antiretroviral resistance (defined below),

4. Participation in another study or program that includes directly observed therapy.

5. 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.

B. Anna Mullen, RN, Phone: 410-502-5088, Email: bmullen1@jhmi.edu

Program for Alcohol and Other Drug Dependencies, Baltimore, Maryland 21205, United States; Recruiting
Tracey Whoolery, MA, Phone: 410-614-2026, Email: twhooler@jhmi.edu
Gregory Lucas, MD, PhD, Principal Investigator

Day Break Methadone Clinic, Baltimore, Maryland 21225, United States; Recruiting
Helen Norman, LPN, Email: helencnorman@msn.com
Sheldon Glass, MD, Principal Investigator

New Hope Treatment Center, Baltimore, Maryland 21223, United States; Terminated

Man Alive, Inc., Baltimore, Maryland 21218, United States; Recruiting
April Stokes, Phone: 410-837-4292, Ext: 1311, Email: astokes1@jhmi.edu
Gregory Lucas, MD, PhD, Principal Investigator

Baltimore VA Drug Dependency Program, Baltimore, Maryland 21201, United States; Recruiting
Walter Williams, Phone: 410-215-1079
Kris Ann Oursler, MD, ScM, Principal Investigator

Starting date: April 2006
Ending date: July 2010
Last updated: April 28, 2009