We conducted a randomized controlled trial comparing clinic-based BUP to referred-treatment for opioid-dependent patients in an HIV clinic. Compared to referred-treatment, the clinic-based BUP strategy was associated with higher participation in opioid agonist therapy over 12 months of follow-up and significantly reduced rates of positive urine drug tests. Additionally, clinic-based BUP subjects attended more visits with their primary care providers during follow-up than referred-treatment subjects. However, we found no evidence that treatment arm was associated with use of antiretroviral therapy or with changes in HIV RNA, CD4 cell counts, or emergency department use and hospitalizations.
It seems likely that streamlined access to opioid agonist therapy was a major mechanism underlying the results we observed. Two weeks after randomization, 84% in clinic-based BUP had initiated opioid agonist therapy compared to just 11% in referred-treatment. Even when expedited by a case-management program, referred-treatment entailed following-up for an intake appointment at a new clinic, completing intake evaluation, and usually waiting until a treatment slot became available. The average wait time for an opioid treatment program assessment visit was 7 days in our study and the average delay between first contact at an opioid treatment program and intake was 12 days in our city during the period the study was conducted. It is notable that rapid treatment intake in the clinic-based BUP arm appeared to yield benefits that persisted out to 12 months.
A number of studies have compared the efficacy of BUP and methadone in head-to-head clinical trials (13
), which was not the goal of our study. Consistent with the tenets of comparative effectiveness research (14
), our objective was to compare the effectiveness of two treatment strategies, clinic-based BUP and referral to an opioid treatment program, that may be available to opioid-dependent HIV-infected patients. Two prior studies randomized individuals recruited from substance abuse treatment settings to treatment in an opioid treatment program or in an office-based setting (15
). One study, which randomized subjects who were receiving methadone at an opioid treatment program to continue in the program or to receive methadone in an office setting, found similar outcomes in the 2 arms, but higher participant satisfaction with the office-based strategy (15
). The second study, which randomized subjects from an opioid treatment program waiting list to either program-based or office-based treatment with BUP, found office-based BUP to be associated with higher retention at 12-weeks and lower rates of opiate-positive urine drug tests compared to program-based BUP (16
Our study differed from these studies in two ways. First, subjects in our study were recruited from a medical setting (HIV clinic) rather than a substance abuse setting. Second, the comparison arm in our study included the step of referring participants to opioid treatment programs, reflecting the process that occurs in clinical practice. Successful referral of substance-dependent individuals from medical care settings to substance abuse treatment is challenging. For example, one observational study that followed 40 patients with substance-related medical conditions after discharge from the hospital, found that only 1 (3%) followed-up with outpatient substance abuse treatment to which he had been referred (17
In addition to lower rates of opioid use, we found that rates of cocaine use were also lower in clinic-based BUP than in referred-treatment. We hypothesize that this difference was due to higher treatment engagement in the former than the latter group, rather than to a pharmacodynamic effect of BUP. In a randomized trial comparing BUP and methadone in opioid-dependent cocaine abusers, BUP was no more effective than methadone in reducing cocaine use (18
Our study has limitations. First, as a single-center study, our results may not generalize to other settings. The treatment model we used was relatively intensive and may not be practical in smaller treatment centers. Additionally, the performance of our control condition, referred-treatment, was inherently tethered to the availability of opioid treatment services in our area. The relative effectiveness of clinic-based BUP may differ in settings in which opioid treatment services are substantially more or less available than in our community. To ensure that referred-treatment was consistently implemented in our study, all subjects allocated to this arm were enrolled in an established case management program in the HIV clinic. Second, the manufacturer provided BUP to sites participating in this demonstration project for use in participants who had no source of payment, eliminating medication insurance coverage as a barrier to treatment in the clinic-based BUP arm. This highlights public health importance of facilitating access to BUP when treatment with this drug is indicated.
Third, owing to the constraints of enrolling from a single clinic, our sample size was small and we enrolled only 78% of our target. This limited our ability to detect smaller, but potentially clinically-significant, differences between the study arms in HIV treatment outcomes. Larger, multicenter, clinical trials of BUP delivery in HIV care settings are warranted to confirm and extend our findings. Fourth, follow-up rates in the study were only fair. However, while sensitivity analyses with pattern-mixture models did provide evidence that differences in opioid agonist therapy participation were sensitive to missing data, the inferences remained the same (i.e., higher participation in clinic-based BUP). Finally, the study arms were imbalanced with regard to recent drug injection, with statistically significantly more subjects in referred-treatment reporting recent injection than in clinic-based BUP. Notably, the study arms were well-matched with regard to demographic and socioeconomic factors, and other indicators of drug use severity including, years of use, history of incarceration, and co-occurring cocaine or alcohol use. Drug injection may be an indicator of more severe drug dependency and be associated with poorer response to treatment (19
), which could bias study outcomes in favor of clinic-based BUP. In post-hoc analyses, we found that outcome differences in the study arms were not appreciably altered by adjustment for baseline injection drug use in multivariate models.
Our study has several implications. Provision of clinic-based BUP should be considered in all HIV treatment settings where opioid dependence is common, and HIV care policy makers should consider including clinic-based BUP as a core quality-of-care measure. Treatment models that integrate substance abuse and medical services have been proposed as a means to improve outcomes for both types of conditions and to improve patient satisfaction (20
). HIV clinics are arguably the medical venue in which the availability of effective clinic-based treatment for opioid dependence can have the greatest impact (24
). Opioid dependence is highly prevalent in many HIV treatment settings and is detrimental to retention in care and adherence to life-saving antiretroviral therapy (25
). Moreover, ongoing drug use in HIV-infected individuals sustains behaviors that risk transmission to others.
In summary, we conducted a randomized trial comparing two treatment strategies for opioid dependent individuals attending an urban HIV clinic. Compared to referred-treatment, we found that clinic-based BUP led to more rapid initiation of opioid agonist therapy, greater use of opioid agonist therapy over 12-month follow-up, lower urine drug test positivity rates for opioids and cocaine, and a higher number of visits with HIV primary care providers during follow-up.