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

P. Todd Korthuis; Ryan R. Cook; Paula J. Lum; Elizabeth Needham Waddell; Hansel Tookes; Pamela Vergara-Rodriguez; Lynn E. Kunkel; Gregory M. Lucas; Allan E. Rodriguez; Sarann Bielavitz; Laura C. Fanucchi; Kim A. Hoffman; Ken Bachrach; Elizabeth H. Payne; Julia A. Collins; Abigail Matthews; Neal Oden; Petra Jacobs; Eve Jelstrom; James L. Sorensen; Dennis McCarty

doi:10.1111/add.15836

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

P. Todd Korthuis
, Ryan R. Cook
, Paula J. Lum
, Elizabeth Needham Waddell
, Hansel Tookes
, Pamela Vergara-Rodriguez
, Lynn E. Kunkel
, Gregory M. Lucas
, Allan E. Rodriguez
, Sarann Bielavitz
, Laura C. Fanucchi
, Kim A. Hoffman
, Ken Bachrach
, Elizabeth H. Payne
, Julia A. Collins
, Abigail Matthews
, Neal Oden
, Petra Jacobs
, Eve Jelstrom
, James L. Sorensen

Dennis McCarty

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English
Pages (from-to)	1961-1971
Number of pages	11
Journal	Addiction
Volume	117
Issue number	7
DOIs	https://doi.org/10.1111/add.15836
State	Published - Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Funding

P.T.K. reports awards from the NIH National Institute on Drug Abuse and serves as principal investigator for NIH‐funded studies that accept donated study medication from Indivior (buprenorphine) and Alkermes (XR‐NTX). Alkermes donated XR‐NTX for CHOICES study participants. H.T. reports grants from Gilead Sciences. Other authors report no conflicts of interest. This article was prepared while P.J. was employed at National Institute on Drug Abuse. P.L. was substantially involved in a design and implementation of CTN0067 (CHOICES) study supported by UG1DA015815, UG1DA013732, UG1DA01372, consistent with her role as Scientific Officer. She had no substantial involvement in the other cited grants. The views and opinions expressed in this manuscript are those of the authors only and do not necessarily represent the views, official policy or position of the US Department of Health and Human Services or any of its affiliated institutions or agencies. This research was supported through cooperative agreements and grants from the US National Institutes of Health National Institute on Drug Abuse (UG1DA015815, UG1DA013732, UG1DA01372, K24DA035684) and Agency for Healthcare Research and Quality (K12HS026370). The authors wish to thank the study participants, HIV clinic staff and outreach workers who contributed to the study’s success.

Funders	Funder number
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse	UG1DA01372, UG1DA015815, K24DA035684, UG1DA013732
Agency for Healthcare Research and Quality	K12HS026370
Gilead Sciences

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Buprenorphine
HIV
extended-release naltrexone
methadone
non-inferiority trial
opioid-related disorders
randomized controlled trials

ASJC Scopus subject areas

Medicine (miscellaneous)
Psychiatry and Mental health

Access to Document

10.1111/add.15836

Cite this

Korthuis, P. T., Cook, R. R., Lum, P. J., Waddell, E. N., Tookes, H., Vergara-Rodriguez, P., Kunkel, L. E., Lucas, G. M., Rodriguez, A. E., Bielavitz, S., Fanucchi, L. C., Hoffman, K. A., Bachrach, K., Payne, E. H., Collins, J. A., Matthews, A., Oden, N., Jacobs, P., Jelstrom, E., ... McCarty, D. (2022). 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. Addiction, 117(7), 1961-1971. https://doi.org/10.1111/add.15836

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title = "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.",

keywords = "Buprenorphine, HIV, extended-release naltrexone, methadone, non-inferiority trial, opioid-related disorders, randomized controlled trials",

author = "Korthuis, \{P. Todd\} and Cook, \{Ryan R.\} and Lum, \{Paula J.\} and Waddell, \{Elizabeth Needham\} and Hansel Tookes and Pamela Vergara-Rodriguez and Kunkel, \{Lynn E.\} and Lucas, \{Gregory M.\} and Rodriguez, \{Allan E.\} and Sarann Bielavitz and Fanucchi, \{Laura C.\} and Hoffman, \{Kim A.\} and Ken Bachrach and Payne, \{Elizabeth H.\} and Collins, \{Julia A.\} and Abigail Matthews and Neal Oden and Petra Jacobs and Eve Jelstrom and Sorensen, \{James L.\} and Dennis McCarty",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Addiction published by John Wiley \& Sons Ltd on behalf of Society for the Study of Addiction.",

year = "2022",

month = jul,

doi = "10.1111/add.15836",

language = "English",

volume = "117",

pages = "1961--1971",

number = "7",

}

Korthuis, PT, Cook, RR, Lum, PJ, Waddell, EN, Tookes, H, Vergara-Rodriguez, P, Kunkel, LE, Lucas, GM, Rodriguez, AE, Bielavitz, S, Fanucchi, LC, Hoffman, KA, Bachrach, K, Payne, EH, Collins, JA, Matthews, A, Oden, N, Jacobs, P, Jelstrom, E, Sorensen, JL & McCarty, D 2022, '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', Addiction, vol. 117, no. 7, pp. 1961-1971. https://doi.org/10.1111/add.15836

TY - JOUR

T1 - HIV clinic-based extended-release naltrexone versus treatment as usual for people with HIV and opioid use disorder

T2 - a non-blinded, randomized non-inferiority trial

AU - Korthuis, P. Todd

AU - Cook, Ryan R.

AU - Lum, Paula J.

AU - Waddell, Elizabeth Needham

AU - Tookes, Hansel

AU - Vergara-Rodriguez, Pamela

AU - Kunkel, Lynn E.

AU - Lucas, Gregory M.

AU - Rodriguez, Allan E.

AU - Bielavitz, Sarann

AU - Fanucchi, Laura C.

AU - Hoffman, Kim A.

AU - Bachrach, Ken

AU - Payne, Elizabeth H.

AU - Collins, Julia A.

AU - Matthews, Abigail

AU - Oden, Neal

AU - Jacobs, Petra

AU - Jelstrom, Eve

AU - Sorensen, James L.

AU - McCarty, Dennis

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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.

KW - Buprenorphine

KW - HIV

KW - extended-release naltrexone

KW - methadone

KW - non-inferiority trial

KW - opioid-related disorders

KW - randomized controlled trials

UR - https://www.scopus.com/pages/publications/85125461966

UR - https://www.scopus.com/pages/publications/85125461966#tab=citedBy

U2 - 10.1111/add.15836

DO - 10.1111/add.15836

M3 - Article

C2 - 35129242

AN - SCOPUS:85125461966

SN - 0965-2140

VL - 117

SP - 1961

EP - 1971

JO - Addiction

JF - Addiction

IS - 7

ER -

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

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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