HIV clinic-based extended-release naltrexone versus treatment as usual for people with HIV and opioid use disorder: a non-blinded, randomized non-inferiority trial.

BACKGROUND AND AIM: Opioid agonist medications for treatment of opioid use disorder (OUD) can improve human immunodeficiency virus (HIV) outcomes and reduce opioid use. We tested whether outpatient antagonist treatment with naltrexone could achieve similar results. DESIGN: Open-label, non-inferiority randomized trial. SETTING: Six US HIV primary care clinics. PARTICIPANTS: A total of 114 participants with untreated HIV and OUD (62% male; 56% black, 12% Hispanic; positive for fentanyl (62%), other opioids (47%) and cocaine (60%) at baseline). Enrollment halted early due to slow recruitment. INTERVENTION: HIV clinic-based extended-release naltrexone (XR-NTX; n = 55) versus treatment as usual (TAU) with buprenorphine or methadone (TAU; n = 59). MEASUREMENTS: Treatment group differences were compared for the primary outcome of viral suppression (HIV RNA ≤ 200 copies/ml) at 24 weeks and secondary outcomes included past 30-day use of opioids at 24 weeks. FINDINGS: Fewer XR-NTX participants initiated medication compared with TAU participants (47 versus 73%). The primary outcome of viral suppression was comparable for XR-NTX (52.7%) and TAU (49.2%) [risk ratio (RR) = 1.064; 95% confidence interval (CI) = 0.748, 1.514] at 24 weeks. Non-inferiority could not be demonstrated, as the lower confidence limit of the RR did not exceed the pre-specified margin of 0.75 in intention-to-treat (ITT) analysis. The main secondary outcome of past 30-day opioid use was comparable for XR-NTX versus TAU (11.7 versus 14.8 days; mean difference = -3.1; 95% CI = -8.7, 1.1) in ITT analysis. Among those initiating medication, XR-NTX resulted in fewer days of opioid use compared with TAU in the past 30 days (6.0 versus 13.6, mean difference = -7.6; 95% CI = -13.8, -0.2). CONCLUSIONS: A randomized controlled trial found supportive, but not conclusive, evidence that human immunodeficiency virus clinic-based extended-release naltrexone is not inferior to treatment as usual for facilitating human immunodeficiency virus viral suppression. Participants who initiated extended-release naltrexone used fewer opioids than those who received treatment as usual.

Promising outcomes from a cognitive behavioral therapy text-messaging intervention targeting drug use, antiretroviral therapy adherence, and HIV risk behaviors among adults living with HIV and substance use disorders.

BACKGROUND: To date, no studies have reported the use of text messaging to deliver cognitive behavioral therapy (CBT) to people living with HIV and substance use disorders. OBJECTIVE: We developed and evaluated a 12-week, CBT-based text-messaging intervention (TXT-CBT) targeting drug use and adherence to antiretroviral therapy (ART) for adults with HIV and comorbid opioid and stimulant use disorders. MATERIALS AND METHODS: Participants were randomly assigned to receive either TXT-CBT (n = 25) or an informational pamphlet (INFO) discussing substance use and medication adherence (n = 25). ART adherence, drug use, and HIV-risk behaviors were assessed at baseline, monthly during treatment, and treatment-end, and were compared between groups using a mixed-model repeated-measures analysis. Injection drug use was examined as a moderator of outcomes. RESULTS: Relative to the INFO group, TXT-CBT participants evidenced increased ART adherence, measured by phone-based unannounced pill counts and biochemically by viral load and CD4 count. TXT-CBT participation was also associated with reductions in opioid use and HIV risk behaviors. While reductions in cocaine use were observed in the TXT-CBT group, relative to the INFO group, other stimulant use did not change. Among people who inject drugs, TXT-CBT produced increases in ART adherence and corresponding changes in viral load, relative to injection drug users in the control condition. CONCLUSIONS: Findings demonstrated promising preliminary evidence for the efficacy of TXT-CBT in improving ART adherence and reducing drug use and HIV-risk behaviors among people with HIV infection and comorbid opioid and stimulant use disorders.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

A cross-sectional assessment of the long term effects of brief strategic family therapy for adolescent substance use.

BACKGROUND: Young adult drug use and law-breaking behaviors often have roots in adolescence. These behaviors are predicted by early drug use, parental substance use disorders, and disrupted and conflict-ridden family environments. AIM: To examine long-term outcomes of Brief Strategic Family Therapy (BSFT) compared to treatment as usual (TAU) in the rates of drug use, number of arrests and externalizing behaviors in young adults who were randomized into treatment conditions as adolescents. DESIGN: 261 of 480 adolescents who had been randomized to BSFT or TAU in the BSFT effectiveness study were assessed at a single time, 3-7 years post randomization. METHODS: Assessments of drug use, externalizing behaviors, arrests and incarcerations were conducted using Timeline Follow Back, Adult Self Report, and self-report, respectively. Drug use, arrests and incarcerations were examined using negative binomial models and externalizing behaviors were examined using linear regression. RESULTS: When compared with TAU, BSFT youth reported lower incidence of lifetime (IRR = 0.68, 95%CI [0.57, 0.81]) and past year (IRR = 0.54, 95%CI [0.40, 0.71]) arrests; lower rates of lifetime (IRR = 0.63, 95%CI [0.49, 0.81]) and past year (IRR = 0.70, 95%CI [0.53, 0.92]) incarcerations; and lower scores on externalizing behaviors at follow-up (B = -0.42, SE = .15, p = .005). There were no differences in drug use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: BSFT may have long term effects in reducing the number of arrests, incarcerations and externalizing problems. These effects could be explained by the improvements in family functioning that occurred during the effectiveness study. This study contributes to the literature by reporting on the long term outcomes of family therapy for adolescent drug abuse.

A randomized trial of concurrent smoking-cessation and substance use disorder treatment in stimulant-dependent smokers.

OBJECTIVE: To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. METHOD: A randomized, 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012. Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual (n = 271) or treatment as usual with smoking-cessation treatment (n = 267). All participants received treatment as usual for substance use disorder treatment. Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300 mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. RESULTS: There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. Participants assigned to treatment as usual with smoking-cessation treatment, relative to those assigned to treatment as usual, had significantly better outcomes for drug-free days at 6-month follow-up (χ(2)(1) = 4.09, P <.05), with a decrease in drug-free days from baseline of -1.3% in treatment as usual with smoking-cessation treatment and of -7.6% in treatment as usual. Participants receiving treatment as usual with smoking-cessation treatment, relative to those receiving treatment as usual, had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs 2.2%; χ(2)(1) = 44.69, P < .001; OR =18.2). CONCLUSIONS: These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen, and may enhance, abstinence from nonnicotine substance use. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01077024.

Brief strategic family therapy versus treatment as usual: results of a multisite randomized trial for substance using adolescents.

OBJECTIVE: To determine the effectiveness of brief strategic family therapy (BSFT; an evidence-based family therapy) compared to treatment as usual (TAU) as provided in community-based adolescent outpatient drug abuse programs. METHOD: A randomized effectiveness trial in the National Drug Abuse Treatment Clinical Trials Network compared BSFT to TAU with a multiethnic sample of adolescents (213 Hispanic, 148 White, and 110 Black) referred for drug abuse treatment at 8 community treatment agencies nationwide. Randomization encompassed both adolescents' families (n = 480) and the agency therapists (n = 49) who provided either TAU or BSFT services. The primary outcome was adolescent drug use, assessed monthly via adolescent self-report and urinalysis for up to 1 year post randomization. Secondary outcomes included treatment engagement (≥2 sessions), retention (≥8 sessions), and participants' reports of family functioning 4, 8, and 12 months following randomization. RESULTS: No overall differences between conditions were observed in the trajectories of self-reports of adolescent drug use. However, the median number of days of self-reported drug use was significantly higher, χ2(1) = 5.40, p < .02, in TAU (Mdn = 3.5, interquartile range [IQR] = 11) than BSFT (Mdn = 2, IQR = 9) at the final observation point. BSFT was significantly more effective than TAU in engaging, χ2(1) = 11.33, p < .001, and retaining, χ2(1) = 5.66, p < .02, family members in treatment and in improving parent reports of family functioning, χ2(2) = 9.10, p < .011. CONCLUSIONS: We discuss challenges in treatment implementation in community settings and provide recommendations for further research.

Transporting clinical research to community settings: designing and conducting a multisite trial of brief strategic family therapy.

This paper describes the development and implementation of a trial of Brief Strategic Family Therapy (BSFT), an evidence-based drug intervention for adolescents, in eight community substance abuse treatment programs. Researchers and treatment programs collaborated closely to identify and overcome challenges, many of them related to achieving results that were both scientifically rigorous and applicable to the widest possible variety of adolescent substance abuse treatment programs. To meet these challenges, the collaborative team drew on lessons and practices from efficacy, effectiveness, and implementation research.

Brief strategic family therapy for adolescent drug abusers: a multi-site effectiveness study.

Brief strategic family therapy (BSFT) is a manualized treatment designed to address aspects of family functioning associated with adolescent drug use and behavior problems (J. Szapocznik, U. Hervis, S. Schwartz, (2003). Brief strategic family therapy for adolescent drug abuse. (NIH Publication No. 03-4751). Bethesda, MD: National Institute on Drug Abuse). Within the National Institute on Drug Abuse's (NIDA's) Clinical Trials Network, BSFT is being compared to treatment as usual (TAU) in a multisite, prospective randomized clinical trial for drug using adolescents and their families in outpatient settings. The effectiveness of BSFT is being compared to TAU in reducing adolescent drug use, conduct problems, and sexually risky behaviors as well as in improving family functioning and adolescent prosocial behaviors. This paper describes the following aspects of the study: specific aims, research design and study organization, assessment of primary and secondary outcomes, study treatments, data analysis plan, and data monitoring and safety reporting.

Characteristics, beliefs, and practices of community clinicians trained to provide manual-guided therapy for substance abusers.

The successful dissemination of empirically supported addiction therapies to community providers requires an appreciation of the characteristics of those practitioners who might be willing participants in this process of technology transfer. Clinicians (N = 66) from 11 community treatment programs associated with six research-clinic partnerships of the National Drug Abuse Clinical Trials Network volunteered to be trained in Motivational Interviewing or Motivational Enhancement Therapy (MET/MI) and were assessed prior to training. The sample of clinicians was heterogeneous in education and credentials, had a high level of counseling experience, reported using a wide range of counseling techniques and orientations, but had limited prior exposure to MET/MI or to the use of treatment manuals of empirically supported therapies. In general, many of the clinicians reported beliefs and techniques that were consistent with their stated theoretical orientation and recovery status. Relatively few participants reported relying on one dominant orientation or set of techniques.

Bridging the research-practice gap in adolescent substance abuse treatment: the case of brief strategic family therapy.

This article presents an empirically validated intervention, Brief Strategic Family Therapy (BSFT), for the treatment of adolescent drug abusers. The BSFT intervention steps and program format are presented. Challenges to implementation in community treatment settings are discussed to identify factors that may facilitate or block the integration of BSFT into community practice settings. In particular, this discussion explores how 3 critical aspects of community treatment programs--program philosophy, program structure, and cost/funding--influence the blending of BSFT into community treatment practice.