Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: A randomized controlled trial

Abstract

Objective

To determine if directly observed antiretroviral therapy (DOT) is more efficacious than self-administered therapy for improving adherence and reducing HIV viral load (VL) among methadone-maintained opioid users.

Design

Two-group randomized trial.

Setting

Twelve methadone maintenance clinics with on-site HIV care in the Bronx, New York.

Participants

HIV-infected adults prescribed combination antiretroviral therapy.

Main outcomes measures

Between group differences at four assessment points from baseline to week 24 in: (1) antiretroviral adherence measured by pill count, (2) VL, and (3) proportion with undetectable VL (<75 copies/ml).

Results

Between June 2004 and August 2007, we enrolled 77 participants. Adherence in the DOT group was higher than in the control group at all post-baseline assessment points; by week 24 mean DOT adherence was 86% compared to 56% in the control group (p < 0.0001). Group differences in mean adherence remained significant after stratifying by baseline VL (detectable versus undetectable). In addition, during the 24-week intervention, the proportion of DOT participants with undetectable VL increased from 51% to 71%.

Conclusions

Among HIV-infected opioid users, antiretroviral DOT administered in methadone clinics was efficacious for improving adherence and decreasing VL, and these improvements were maintained over a 24-week period. DOT should be more widely available to methadone patients.

Introduction

Though deaths among persons with AIDS have decreased with combination antiretroviral therapy, death rates among drug users have decreased less markedly (Tang et al., 2008). Disproportionately worse HIV treatment outcomes among drug users compared to non-drug users have been attributed partly to poor medication adherence (Arnsten et al., 2002, Malta et al., 2008). Though many adherence-improving interventions exist, few have focused specifically on drug users.

Programs providing directly observed therapy (DOT) for tuberculosis have been shown to improve medication adherence and clinical outcomes, and to reduce the incidence of drug resistance (Chaulk and Kazandjian, 1998, Weis et al., 1994). Since these same goals apply to HIV treatment, it is reasonable to extend the DOT model to antiretroviral therapy for HIV, particularly among populations at risk for non-adherence (Lanzafame et al., 2000, Mitty et al., 2002, Ford et al., 2009). Antiretroviral DOT programs have been successfully implemented in community settings using outreach workers (Altice et al., 2004, Behforouz et al., 2004, Khanlou et al., 2003, Ma et al., 2008, Mitty et al., 2005, Wohl et al., 2006), and in settings with infrastructures allowing frequent contact, such as prisons (Babudieri et al., 2000, Kirkland et al., 2002), housing facilities (Tinoco et al., 2004), and methadone clinics (Clarke et al., 2002, Conway et al., 2004, Lucas et al., 2004). While these studies have demonstrated feasibility and acceptability, few have examined efficacy using randomized designs, and none has evaluated methadone clinic-based DOT in a randomized trial.

Methadone clinics provide a promising infrastructure for DOT because federal regulations mandate that patients receive their daily methadone dose at one clinic, and the majority of doses are directly observed by nurses. However, providing co-located substance abuse treatment and HIV medical care is challenging because addiction medicine and HIV care are usually provided by specialists who may not have expertise in both fields. Though co-located medical care and methadone treatment improves outcomes among patients with tuberculosis, HIV, and Hepatitis C (Batki et al., 2002, Gourevitch et al., 2007, Litwin et al., 2009, Mauss et al., 2004), current payment policies promote segregation of substance abuse treatment and HIV care.

Support for Treatment Adherence Research through Directly Observed Therapy (STAR*DOT) was a randomized controlled trial designed to test the efficacy of directly observed antiretroviral therapy (DOT) provided on-site in methadone clinics. Our objective was to determine if DOT is more efficacious than self-administered antiretroviral therapy for improving adherence and reducing HIV viral load (VL) among methadone-maintained drug users. We hypothesized that at the end of the 24-week intervention period, participants in the DOT intervention group would have higher adherence and lower VL than participants in the treatment as usual (TAU) control group.