Directly observed therapy (DOT) is an effective approach for the treatment of tuberculosis among substance users. We have adapted this model to treat human immunodeficiency virus infection. Our experience suggests that community-based, modified DOT should be explored further as a means to treat infectious diseases and chronic medical illnesses for persons with drug dependence; it may be especially pertinent for the treatment of hepatitis C virus infection. DOT can both optimize adherence and provide a way to offer psychosocial support and linkages to social, addiction, psychiatric, and other services, to help address many of the challenges faced by persons with substance abuse disorders.
Persons with drug dependence face myriad daunting challenges in receiving medical care. From the patient's standpoint, there is an inner battle that may include decreased motivation, lowered self-esteem, substance abuse, and mental illness. Other challenges are imposed externally and may include poor health care for those who lack insurance or are underinsured, stigma against drug users, and a lack of information and resources. Substance users have a significantly higher prevalence of a host of infectious diseases, including HIV, hepatitis B virus, and hepatitis C virus (HCV) infections, sexually transmitted infections, tuberculosis, bacterial pneumonia, and bloodstream infections. In addition, there is significant chronic medical illness associated with substance use, including psychiatric, neurological, cardiac, pulmonary, renal, and hepatic diseases.
Directly Observed Therapy (Dot) for Tuberculosis
In the face of these challenges, a model of care has worked extremely well for persons with both past and current substance use: DOT for the treatment of tuberculosis. DOT for tuberculosis has worked in many difficult circumstances, including inner-city Baltimore, where there are high rates of crack cocaine use, homelessness, and poverty . It has been effective among persons who are socially unstable and living on the street, as well as for persons with psychiatric illness and ongoing substance use [2, 3].
Many important lessons have been learned from the treatment of tuberculosis in general and from the use of DOT for tuberculosis, specifically the following:
among communities with high rates of substance use, routine screening for tuberculosis is effective in identifying persons with disease;
the treatment and transmission of tuberculosis are linked, and good treatment of tuberculosis dramatically limits transmission;
treatment for tuberculosis must be community-based (if treatment is located entirely within academic medical centers or is not easily accessible, it will not be effective);
multidrug therapy is the cardinal rule for the treatment of tuberculosis; and
DOT clearly works, even among persons who have difficulty adhering to other medical therapies.
These same lessons can be applied to the development of care programs for other infectious diseases that have a higher prevalence among substance users, including HIV and HCV infection. Routine screening is the most effective means of diagnosis for populations at risk. Treatment of HIV infection lowers HIV load, both within the plasma and within the genital tract. Lower HIV loads in plasma correlate with decreased rates of sexual transmission . In all probability, antiretroviral treatment of HIV infection results in significant decreases in transmission . Anti-HCV medications may lower or even eliminate serum HCV RNA, thus reducing infectivity . Community-based treatment programs for HIV and HCV infection that are readily accessible to substance-using populations are likely to be acceptable and feasible to implement. A combination of medications is necessary not only for tuberculosis but also for HIV and HCV. Future therapies for HCV infection likely will continue to rely on multiple medications to achieve better rates of sustained virological response .
Methods and Case Study
Within the past 4 years, our group and others have developed, piloted, and evaluated DOT programs for the treatment of HIV infection [8–13]. The following case study illustrates both the successes and challenges of providing community-based DOT for HIV-infected persons who are unable to adhere to treatment with antiretrovirals because of active substance abuse, social instability (e.g., homelessness), and/or psychiatric illness.
In 2002, a 42-year-old woman with a history of depression, HCV infection, and polysubstance addiction to heroin, cocaine, and alcohol was seen in our HIV clinic for evaluation. She had a baseline CD4 cell count of 167 cells/mm3 and a plasma HIV load of 4.4 logs and had been prescribed combination antiretroviral therapy by her medical provider many times in the past. At each attempt, she had indicated a willingness to begin and adhere to treatment but, on subsequent visits, had never achieved significant virus suppression. Resistance analysis by genotype revealed resistance to multiple antiretroviral agents. A once-daily antiretroviral combination was prescribed, and she was enrolled in the DOT program.
Although she was intermittently homeless, outreach workers were able to visit with her 5 days/week. After 3 months on the program, her plasma HIV load was undetectable, and her CD4 cell count increased to 230 cells/mm3. This was the first time that she had achieved an undetectable HIV load since 1997. She was subsequently incarcerated for 30 days and, soon after her release from prison, was homeless again. She developed nausea and vomiting, which might have been related to substance use and/or withdrawal but which she attributed to the antiretroviral medications. She decided to stop her medications. Through the combined efforts of the DOT team, her case manager, and the clinic staff, she was admitted to a housing program for HIV-seropositive persons, and DOT was begun again with the assistance of the program staff. As a result, her HIV load returned to an undetectable level. One year after enrollment in the program, she remains in this supportive environment and has maintained an undetectable HIV load.
In our pilot DOT programs , the treating physician prescribes a once-daily highly active antiretroviral therapy (HAART) regimen to the participant. All enrolled subjects have self-reported substance abuse within 90 days and/or severe mental illness, as well as a history of poor adherence to HAART, as determined by either the participant or the primary care provider. Participants obtain prescribed medications at their own pharmacy and give them to the study nurse, who prepares them to be delivered by a near-peer outreach worker.
All of our outreach workers are from nearby communities with a relatively high prevalence of HIV infection and are comfortable in diverse inner-city settings. Although they are not case managers, outreach workers are trained in issues of safety, confidentiality, and procedures for making referrals for supportive services as needed. An outreach worker delivers medications to participants at the time and place of the participant's choice. Initial visits are scheduled for 5–7 days/week and then are tapered on the basis of HIV load response and the desire of the participant. DOT in this pilot program to treat HIV is significantly different from DOT for tuberculosis in that the program encourages a combination of self-administered doses along with observed doses. This strategy encourages patients to successfully self-administer medications over time.
Initial results from our pilot DOT program have been encouraging. Of the first 51 participants enrolled, the mean duration of study participation is 6.4 months. About 31% are African American, 18% are Hispanic, and 47% are white. Fifty-one percent have a history of incarceration, and 86% have a history of addiction. Fifty-three percent were actively using heroin or cocaine while enrolled in the program. Among persons who were maintained on the program for 6 months, the median decrease in HIV load was >1.5 logs, with a median increase in CD4 cell count of 77 cells/mm3.
An evaluation of the first 13 participants maintained on the program for 6 months [13, 14] showed that all persons thought that the outreach workers “had helped me take my medications.” Sixty-six percent thought that the program had helped them “not to miss any clinical appointment.” At the end of 6 months on the program, 83% believed that they could take their HIV medications every day, even if the outreach worker did not visit. Retention in the study was greatly enhanced by flexibility, allowing visits to be tapered over the course of the week from 5 to 3 to 2 and even to 1, depending on the circumstances and requests of the participants.
As our program evolved, we found that it was important for patients who discontinued medications (because of either their own wishes or instructions from their primary care physician) to maintain contact with the outreach workers, even when not taking their medications. In addition, the DOT staff maintained contact with participants if they were incarcerated or entered a short-term medical or substance abuse treatment program. The rationale was that this would aid in linking persons with DOT on release back into the community.
On the basis of our experiences, we have reached the following conclusions:
modified DOT (MDOT) can provide an effective mechanism to deliver HAART for many persons who have not been successful in self-administration of HIV medications;
MDOT needs to provide flexibility and empower patients to self-administer medications over time;
MDOT should accommodate the tremendous instability in the lives of participants, which may include frequent changes in living conditions because of incarceration, cycling in and out of detoxification programs, and unstable housing status;
MDOT for HIV infection is modified and is clearly distinct from DOT for tuberculosis in that not all doses are observed; and
MDOT is an important venue for referral for other support services and for providing emotional support through the caring intervention of near-peer outreach workers.
Applying Dot to the Treatment of HCV Infection and Other Diseases
This approach can be modified for the treatment of multiple other illnesses among persons with substance use disorders such as HCV infection, depression, or addiction itself. For example, the advent of pegylated IFN provides an excellent rationale for patients undergoing treatment for HCV infection to receive injections delivered by health-care providers in an observed setting. Adherence counseling regarding ribavirin, referral for social services, and intensive support all can be provided during this visit. Ribavirin and other daily medications can be “pill-packed” in medication boxes on a weekly basis.
In general, DOT-type interventions will need to be modified for various communities and different types of participants. Some may not agree to home visits because of concerns about confidentiality. Programs that provide interventions among adolescents would be very different from those working with older participants. Programs for persons being released from prison, as well as those for women with children, are also needed and will need to be targeted to these specific groups.
Community-based, MDOT programs can decrease many of the challenges faced by persons with substance use disorders in need of medical care for infectious or chronic diseases. MDOT can provide a way to offer psychosocial support and linkages to addiction, mental health, and other services to help persons overcome many of the social challenges that they confront. In addition, the personal and emotional support offered by outreach workers can help improve patients' self-esteem, enable them to take greater responsibility for their own health, and provide hope that illness can be overcome with improved quality of life.
We thank Patricia Schreiber for assisting with manuscript preparation.
Financial support. Lifespan-Tufts-Brown Center for AIDS Research (National Institutes of Health, National Institute of Allergy and Infectious Disease, grant 5P30 AI-42853), National Institute of Drug Abuse (grant R01 DA-13767), Bristol-Myers Squibb, Roche Laboratories, and GlaxoSmithKline.
Potential conflicts of interest. L.E.T.: Grant support from and speakers' bureau for Roche Laboratories; T.P.F. and J.M.: no conflicts.