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

Abstract

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.

Suicidality as a Predictor of Overdose among Patients with Substance Use Disorders

“…We analyzed data from eight multicenter CTN trials that included 2543 participants [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Only 2541 participants were included in the analysis (2 participants were excluded due to missing data).…”

“…Given the correlation between depression and suicidality, the prevalence of baseline depression was also assessed by creating a binary indicator of depression using the instrument that had been part of each trial’s procedures. Depression measures included the 9-item Patient Health Questionnaire (PHQ-9 [ 26 ]: CTN0067 [ 38 , 46 ], CTN0068 [ 39 , 47 ]), the 18-item Brief Symptom Inventory (BSI-18 [ 48 ]: CTN0049 [ 33 , 41 ], CTN0064 [ 37 , 45 ]), the Addiction Severity Index Lite (ASI Lite [ 49 ];CTN0037 [ 32 , 40 ], CTN0051 [ 34 , 42 ]), the Medical and Psychiatric History (CTN0054 [ 36 , 44 ]), and the Hospital Anxiety and Depression Scale (HADS [ 50 ]: CTN0053 [ 35 , 43 ]). Because lifetime heroin use [ 51 ], recent alcohol and benzodiazepine use [ 52 ], and past psychiatric history [ 53 ], increase risk of overdose, these factors were also included as covariates in the model.…”

“…Each of these covariates was assessed by creating binary variables of each distinct instrument or question across the 8 trials. The assessment of lifetime use of heroin included the Addiction Severity Index Lite (ASI Lite [ 49 ]: 0037 [ 32 , 40 ], 0049 [ 33 , 41 ], 0051 [ 34 , 42 ], 0064 [ 37 , 45 ], 0067 [ 38 , 46 ]) and the Alcohol and Substance History (0054 [ 36 , 44 ], 0068 [ 39 , 47 ]). One trial, CTN 0054, did not assess lifetime use of heroin.…”

“…Recent alcohol and benzodiazepine use was determined by creating a binary indicator using each trial’s instrument to assess this variable. The assessment of alcohol and benzodiazepine use was determined by the ASI Lite (0037 [ 32 , 40 ], 0049 [ 33 , 41 ], 0051 [ 34 , 42 ], 0064 [ 37 , 45 ], 0067 [ 38 , 46 ]), and the DSM-5 checklist [ 54 ] (CTN0054 [ 36 , 44 ], CTN0053 [ 35 , 43 ], CTN0068 [ 39 , 47 ]). Psychiatric history exclusive of depression was determined as a binary indicator, using each trial’s instrument to assess this variable.…”

“…Psychiatric history exclusive of depression was determined as a binary indicator, using each trial’s instrument to assess this variable. The assessment of psychiatric history included the Medical History Form (0051 [ 34 , 42 ], 0054 [ 36 , 44 ], 0067 [ 38 , 46 ], 0068 [ 39 , 47 ]), ASI Lite (CTN 0037 [ 32 , 40 ]), Additional Psychiatric Diagnosis Form (CTN0064 [ 37 , 45 ]), and the Mini International Neuropsychiatric Interview, version 6.0 (MINI 6.0 [ 55 ]: 0053 [ 35 , 43 ]). For participants in CTN0049, psychiatric diagnosis was considered via two instruments.…”