Rationale, design, and sample characteristics of a randomized controlled trial of directly observed antiretroviral therapy delivered in methadone clinics☆
Introduction
Optimal antiretroviral adherence is necessary to minimize replication of drug resistant virus and achieve the clinical benefits of HIV treatment. Current and former drug users have disproportionately worse HIV treatment outcomes compared to non-drug users, in part because of poor medication adherence [1], [2], [3]. Though numerous adherence-improving interventions have been evaluated in randomized trials, very few have addressed HIV-infected drug users [4].
Programs providing directly observed therapy (DOT) for tuberculosis have been shown to improve medication adherence and clinical response, and to reduce the incidence of drug resistant infection [5], [6]. Since these same goals apply to HIV treatment, extending the tuberculosis DOT model to antiretroviral therapy for HIV is reasonable. However, treatment for tuberculosis is time limited and dosing can be two or three times weekly for much of the treatment duration, while antiretroviral therapy for HIV is long-term and requires treatment with once or twice daily dosing. Because of the requirement for chronic daily treatment, antiretroviral DOT programs have been implemented in community settings using outreach workers [7], [8], or in settings with infrastructures allowing frequent contact, such as prisons [9] or methadone maintenance clinics [10], [11].
Methadone maintenance clinics are a particularly promising setting for DOT programs because federal regulations mandate patients to receive their daily methadone dose at the clinic, and the majority of doses are directly observed by nurses. Prior observational studies of methadone-clinic-based antiretroviral DOT programs suggest that they are feasible, acceptable, and improve rates of viral suppression [10], [12]. However we know of no randomized clinical trials evaluating antiretroviral DOT administered on-site in a methadone clinic.
We developed the Support for Treatment Adherence Research through Directly Observed Therapy (STAR⁎DOT) trial, a randomized controlled trial, to test the efficacy of directly observed antiretroviral therapy provided on-site at a methadone clinic during a 24-week study period. Our objective was to determine if DOT is more efficacious than self-administered antiretroviral therapy for reducing HIV viral load, improving antiretroviral adherence, and reducing HIV drug resistance, among antiretroviral-naïve or experienced opioid dependent methadone-maintained drug users. In this paper, we provide a detailed methodological description of the STAR⁎DOT trial, which may serve as a template for investigators designing DOT trials. In addition, we discuss pertinent safety and confidentiality issues that can guide protocols for studies among HIV-infected drug users receiving methadone for opioid dependence. We also report baseline characteristics of the study population.
Section snippets
Study design
The STAR⁎DOT trial was a randomized controlled trial in which methadone-maintained participants were randomly assigned to one of two groups: treatment as usual (TAU) or directly observed therapy (DOT) for treatment of HIV. Participants in the TAU (control) group received standard adherence support (described below), including HIV adherence counseling and self-administered their antiretroviral medications. Participants in the DOT (intervention) group received standard adherence support plus
Results
Screening and baseline interviews occurred between June 2004 and September 2007. All STAR⁎DOT trial participants had completed the 24-week intervention by February 2008.
A total of 3231 participants were screened. Of these, 97 were eligible and 77 enrolled in the study (Fig. 1). The main reasons for exclusion after the initial screener and review of medical and laboratory data were HIV negative (77%) or not on antiretroviral therapy (29%). Of the 77 enrollees, 39 were randomized to the DOT arm
Discussion
STAR⁎DOT represents the first randomized controlled trial of a directly observed antiretroviral program in a methadone program. Our trial is consistent with prior work on the feasibility of DOT programs in methadone clinics [10], [11], [23], and extends this research by randomizing participants to a DOT intervention or a treatment-as-usual control condition. Outcomes from the STAR⁎DOT trial will contribute to current knowledge by evaluating the efficacy of DOT for reducing HIV viral load,
Acknowledgements
The authors thank Nina Cooperman, Joseph Hecht, Maite Villanueva, Metta Cantlo, Amanda Carter, Megha Ramaswamy, Francesca Parker, Laxmi Modali, Hillel Cohen, and Moonseong Heo for assistance with protocol development, pharmacy coordination, data collection and management, and statistical consultation. The trial was dependent on the cooperation of the medical providers, nurses, and patients at the Albert Einstein College of Medicine and Montefiore Medical Center Division of Substance Abuse. We
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Integrating HIV and substance misuse services: a person-centred approach grounded in human rights
2022, The Lancet PsychiatryCitation Excerpt :Illustrative examples are shown in panel 2. Several models have adopted a more holistic approach, in which HIV services are provided by multidisciplinary teams of medical staff including specialist physicians, counsellors, nurses, case workers, and social workers.83–86 In some models, staff help patients to access medical insurance or social benefits and other services.
The Quest for an Effective Adherence Intervention: A DOT-cART Case Study
2014, Journal of the Association of Nurses in AIDS CareSocial Support Networks and Primary Care Use by HIV-Infected Drug Users
2013, Journal of the Association of Nurses in AIDS CareCitation Excerpt :All participants gave written informed consent. The STAR*DOT study has been described in more detail elsewhere (Berg, Litwin, Li, Heo, & Arnsten, 2011; Berg et al., 2009). The analysis reported in this article includes data from the STAR*DOT baseline assessment, which consisted of a survey administered using Audio Computer-Assisted Self-Interview (ACASI) technology.
Directly observed antiretroviral therapy eliminates adverse effects of active drug use on adherence
2012, Drug and Alcohol DependenceCitation Excerpt :We hypothesized that: (1) opiate, cocaine and polysubstance use decrease antiretroviral adherence; and that (2) the association between drug use and adherence is moderated by antiretroviral DOT. The STAR*DOT trial has been previously described (Berg et al., 2011, 2009). Briefly, participants were randomized to antiretroviral DOT or treatment as usual (TAU) for 24 weeks.
Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: A randomized controlled trial
2011, Drug and Alcohol DependenceCitation Excerpt :These affiliated clinics provide care for approximately 3500 opioid-dependent patients, of whom 10–15% is HIV-infected. A detailed description of study procedures has been described previously (Berg et al., 2009). Patients were eligible for inclusion if they: were HIV-infected and prescribed antiretroviral therapy; received HIV treatment at their methadone clinic or a closely affiliated site; attended the methadone clinic 5 or 6 days per week (hereafter, 5- or 6-day pick-up schedule); were on a stable dose of methadone for 2 weeks prior to baseline; and were genotypically sensitive to their prescribed antiretroviral regimen.
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This work was funded by National Institutes of Health grants R01 DA015302 awarded to Dr. Arnsten, K23 DA021087 awarded to Dr. Berg, and a Center for AIDS Research grant (P30 A1051519) awarded to the Albert Einstein College of Medicine of Yeshiva University.