The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.

BACKGROUND: In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics. OBJECTIVES: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB. METHODS: We prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates. RESULTS: The study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27-48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%. CONCLUSION: No clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial.

Multilevel strategies to end HIV for young couples in Cape Town: Study protocol for a cluster randomized trial.

This protocol presents a multilevel cluster randomized study in 24 communities in Cape Town, South Africa. The study comprises four specific aims. Aim 1, conducted during the formative phase, was to modify the original Couples Health CoOp (CHC) intervention to include antiretroviral therapy/pre-exposure prophylaxis (ART/PrEP), called the Couples Health CoOp Plus (CHC+), with review from our Community Collaborative Board and a Peer Advisory Board. Aim 1 has been completed for staging the trial. Aim 2 is to evaluate the impact of a stigma awareness and education workshop on community members' attitudes and behaviors toward young women and men who use AODs and people in their community seeking HIV services (testing/ART/PrEP) and other health services in their local clinics. Aim 3 is to test the efficacy of the CHC+ to increase both partners' PrEP/ART initiation and adherence (at 3 and 6 months) and to reduce alcohol and other drug use, sexual risk and gender-based violence, and to enhance positive gender norms and communication relative to HIV testing services (n = 480 couples). Aim 4 seeks to examine through mixed methods the interaction of the stigma awareness workshop and the CHC+ on increased PrEP and ART initiation, retention, and adherence among young women and their primary partners. Ongoing collaborations with community peer leaders and local outreach staff from these communities are essential for reaching the project's aims. Additionally, a manualized field protocol with regular training, fidelity checks, and quality assurance are critical components of this multilevel community trial for successful ongoing data collection. Trial registration. Clinicaltrials.gov Registration Number: NCT05310773. Pan African Trials: pactr.samrc.ac.za/ Registration Number: PACTR202205640398485.

Outcomes of substance use and sexual power among adolescent girls and young women in Cape Town: Implications for structural and cultural differences.

Adolescent girls and young women (AGYW) in South Africa experience contextual barriers to HIV risk reduction including incomplete schooling, unintended pregnancy, substance use, and gender-based violence. A cluster randomised trial in Cape Town allocated 24 Black and Coloured communities to a gender-focused HIV risk-reduction intervention or HIV testing, with 500 AGYW total enrolled. We evaluated intervention efficacy by comparing mean differences overall, by community population group (Black and Coloured) and among those with structural barriers based on neighbourhood, education, and employment (n = 406). Both arms reported reductions in alcohol, cannabis, and condomless sex, with no intervention efficacy overall. Among AGYW with barriers, intervention participants reported fewer days of methamphetamine use at 6 months (t(210) = 2·08, p = ·04). In population group analysis, we found intervention effects on alcohol and sexual communication. Intervention participants in Black communities had fewer days of alcohol use at 12 months (t(136) = 2·10, p = ·04). Sexual discussion (t(147) = -2·47, p = ·02) and condom negotiation (t(146) = -2·51, p = ·01) increased for intervention participants at 12 months in Coloured communities. Gender-focused interventions must address population group differences and intersecting barriers to decrease substance use and increase education, skills, and sexual health protection.

Binge drinking and condom negotiation behaviours among adolescent girls and young women living in Cape Town, South Africa: sexual control and perceived personal power.

BACKGROUND: Condom use among young people in South Africa has declined in recent years and adolescent girls and young women continue to bear the highest incidence of HIV in the country. Young women who have dropped out of school may be more at risk because of traditional gender norms that create substantial power imbalances and a lack of power to negotiate condom use with their male partners, especially when using alcohol and other drugs. METHODS: This study presents an analysis of baseline data provided by 500 adolescent girls and young women (AGYW) from Cape Town communities between November 2016 and November 2018 who were reached for a cluster-randomised trial conducted to assess the efficacy of an evidence-based, young woman-focused intervention seeking to reduce HIV risk and substance use behaviours. The analysis focuses on associations between binge drinking, condom use, and sexual negotiation, including impaired sex (any substance use at last sex). RESULTS: AGYW who reported frequent condom negotiation with their partners were 8.92 times (95% CI: [4.36, 18.24]) as likely to use a condom when alcohol or other drugs were not used at last sex and 5.50 times (95% CI: [2.06, 14.72]) as likely when alcohol or other drugs were used at last sex (p < 0.05). AGYW who reported frequent binge drinking in the past month (n = 177) had significantly reduced odds of condom use at last sex, irrespective of whether the sex was impaired (OR 0.60, 95% CI: [0.49, 0.73]) or not impaired (OR 0.69, 95% CI: [0.60, 0.81]). DISCUSSION: The findings highlight the need for interventions that reach AGYW in South Africa by specifically aiming to educate AGYW about the effect of binge drinking on negotiating power in their relationships, thus providing them with the knowledge and skills to increase agency regarding condom use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02974998 (recruitment completed). 29/11/2016.

Patient and provider perceptions of the relationship between alcohol use and TB and readiness for treatment: a qualitative study in South Africa.

Background: Unhealthy alcohol use is widespread in South Africa and has been linked to tuberculosis (TB) disease and poor treatment outcomes. This study used qualitative methods to explore the relationship between TB and alcohol use during TB treatment. Methods: Focus groups (FGs) were conducted with 34 participants who had previous or current drugsusceptible TB and self-reported current alcohol use. Eight interviews were conducted with healthcare workers who provide TB services in Worcester, South Africa. Results: In this rural setting, heavy episodic drinking is normalized and perceived to be related to TB transmission and decreased adherence to TB medication. Both healthcare workers and FG participants recommended the introduction of universal screening, brief interventions, and referral to specialized care for unhealthy alcohol use. However, participants also discussed barriers to the provision of these services, such as limited awareness of the link between alcohol and TB. Healthcare workers also specified resource constraints while FG participants or patients mentioned widespread stigma towards people with alcohol concerns. Both FG participants and health providers would benefit from education on the relationship between TB and unhealthy alcohol use as well and had specific recommendations about interventions for alcohol use reduction. Healthcare workers also suggested that community health worker-delivered interventions could support access to and engagement in both TB and alcohol-related services. Conclusion: Findings support strengthening accessible, specialized services for the identification and provision of interventions and psychosocial services for unhealthy alcohol use among those with TB.

Latent class analysis of substance use typologies associated with mental and sexual health outcomes among sexual and gender minority youth.

Little is known about sexual and gender minority youth (SGMY) who have sex with men's unique patterns of substance use, even though they are at risk for substance use and adverse mental and other health outcomes. We used latent class analysis to examine typologies of substance use and multinomial logistic regression to investigate mental health outcomes (depression and anxiety) and HIV/STI testing correlates associated with different classes of substance use in a sample of SGMY who have sex with men in the USA and use substances (n = 414) who participated in an online survey. The average age was 22.50 years old (SD = 3.22). A four-class solution was identified representing: 'depressant and stimulant use' (3.4%), 'high polysubstance use' (4.6%), 'low substance use with moderate cannabis use' (79.2%), and 'high cannabis, stimulant and alcohol use' (12.8%). Membership to a specified substance use class varied by age, previous arrest, gender identity, anxiety, and lifetime HIV testing. Multivariate logistic regression results indicated that participants in the high polysubstance use (AOR = 5.48, 95% CI 1.51, 19.97) and high cannabis use class (AOR = 3.87, 95% CI 1.25, 11.94) were significantly more likely than those in the low substance use with moderate cannabis use class to report previous arrest. Those in the high polysubstance use class were also significantly less likely to have been tested for HIV than those in the low substance use with moderate cannabis use class (AOR = 0.21, 95% CI 0.05, 0.93). Findings will guide the development and implementation of tailored approaches to addressing the intersection of substance use and HIV risk among SGMY.

Factors associated with current substance use among a sample of homeless individuals in Cape Town, South Africa: a secondary data analysis.

Homelessness is a global issue that is often associated with substance use. Research on this relationship in low- to middle-income countries (LMIC) is limited. We aimed to explore which factors are associated with substance use through secondary data analysis of a sample of 472 adults who attended services for homeless individuals in Cape Town, South Africa. Logistic regression was utilized to investigate if length of homelessness was associated with current alcohol and drug use respectively, after accounting for other factors. Current drug use (44.9%) was higher than current alcohol use (22.7%) and the most prevalent lifetime drug was methamphetamine (32.6%). After adjusting for lifetime substance use, and source of income, length of homelessness was not significantly associated with current alcohol use (less than on year: OR = 2.60; 95% CI: 0.78-8.66; one or more years: OR = 0.90; 95% CI: 0.32-2.57) or current drug use (less than one year: OR = 0.78; 95% CI: 0.41-1.47; one year or more: OR = 1.04; 95% CI: 0.56-1.93). These results highlight the need to further investigate other factors that may influence current alcohol or drug use among populations at risk of being homeless, and to utilize validated measures of substance and other mental health conditions.

Methods for handling missing data in serially sampled sputum specimens for mycobacterial culture conversion calculation.

BACKGROUND: The occurrence and timing of mycobacterial culture conversion is used as a proxy for tuberculosis treatment response. When researchers serially sample sputum during tuberculosis studies, contamination or missed visits leads to missing data points. Traditionally, this is managed by ignoring missing data or simple carry-forward techniques. Statistically advanced multiple imputation methods potentially decrease bias and retain sample size and statistical power. METHODS: We analyzed data from 261 participants who provided weekly sputa for the first 12 weeks of tuberculosis treatment. We compared methods for handling missing data points in a longitudinal study with a time-to-event outcome. Our primary outcome was time to culture conversion, defined as two consecutive weeks with no Mycobacterium tuberculosis growth. Methods used to address missing data included: 1) available case analysis, 2) last observation carried forward, and 3) multiple imputation by fully conditional specification. For each method, we calculated the proportion culture converted and used survival analysis to estimate Kaplan-Meier curves, hazard ratios, and restricted mean survival times. We compared methods based on point estimates, confidence intervals, and conclusions to specific research questions. RESULTS: The three missing data methods lead to differences in the number of participants achieving conversion; 78 (32.8%) participants converted with available case analysis, 154 (64.7%) converted with last observation carried forward, and 184 (77.1%) converted with multiple imputation. Multiple imputation resulted in smaller point estimates than simple approaches with narrower confidence intervals. The adjusted hazard ratio for smear negative participants was 3.4 (95% CI 2.3, 5.1) using multiple imputation compared to 5.2 (95% CI 3.1, 8.7) using last observation carried forward and 5.0 (95% CI 2.4, 10.6) using available case analysis. CONCLUSION: We showed that accounting for missing sputum data through multiple imputation, a statistically valid approach under certain conditions, can lead to different conclusions than naïve methods. Careful consideration for how to handle missing data must be taken and be pre-specified prior to analysis. We used data from a TB study to demonstrate these concepts, however, the methods we described are broadly applicable to longitudinal missing data. We provide valuable statistical guidance and code for researchers to appropriately handle missing data in longitudinal studies.

Gender and Context Matter: Behavioral and Structural Interventions for People Who Use Alcohol and Other Drugs in Africa.

Heavy alcohol consumption and other drug use are prominent across Africa and increase the risk of exposure to violence, HIV acquisition, and other life-threatening injuries. This review synthesizes evidence on alcohol and other drug (AOD) interventions in Africa; evaluates the differences between interventions that do and do not specifically target populations that use AODs; and highlights the impact of comprehensive vs. brief interventions and those that address syndemic issues from a gender and contextualized lens. Literature searches were conducted to identify research outcomes of randomized interventions published between January 2010 and May 2022 that address AOD use in Africa. Thirty-five full-text articles were included in this review. Most of the identified research studies were concentrated in a few countries. Most studies were conducted in South Africa. Many of the studies comprised brief interventions. However, the most comprehensive interventions were the most effective for AOD outcomes. Several studies indicated the importance of addressing AOD use alongside gender-based violence, mental health needs, gender roles, and other social determinants that affect health outcomes. Intervening on AOD use and addressing social determinants from a gender and contextually relevant perspective is essential to ensuring the long-term health and well-being of people in Africa.

Transmission Of Tuberculosis Among illicit drug use Linkages (TOTAL): A cross-sectional observational study protocol using respondent driven sampling.

People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess the risk of TB exposure and disease progression. Research also is needed to assess mechanisms for accelerated TB transmission in this population. This study aims to 1) assess the rate of TB exposure, risk of disease progression, and disease burden among PWUD; 2) estimate the proportion of active TB cases resulting from recent transmission within this network; and 3) evaluate whether PWUD with TB disease have physiologic characteristics associated with more efficient TB transmission. Our cross-sectional, observational study aims to assess TB transmission through illicit drug use networks, focusing on methamphetamine and Mandrax (methaqualone) use, in a high TB burden setting and identify mechanisms underlying accelerated transmission. We will recruit and enroll 750 PWUD (living with and without HIV) through respondent driven sampling in Worcester, South Africa. Drug use will be measured through self-report and biological measures, with sputum specimens collected to identify TB disease by Xpert Ultra (Cepheid) and mycobacterial culture. We will co-enroll those with microbiologic evidence of TB disease in Aim 2 for molecular and social network study. Whole genome sequencing of Mycobacteria tuberculosis (Mtb) specimens and social contact surveys will be done for those diagnosed with TB. For Aim 3, aerosolized Mtb will be compared in individuals with newly diagnosed TB who do and do not smoke illicit drug. Knowledge from this study will provide the basis for a strategy to interrupt TB transmission in PWUD and provide insight into how this fuels overall community transmission. Results have potential for informing interventions to reduce TB spread applicable to high TB and HIV burden settings. Trial registration: Clinicaltrials.gov Registration Number: NCT041515602. Date of Registration: 5 November 2019.

'We have goals but [it is difficult]'. Barriers to antiretroviral therapy adherence among women using alcohol and other drugs living with HIV in South Africa.

BACKGROUND: Women living with HIV who misuse alcohol and live in economically disadvantaged settings in South Africa experience a multitude of contextual barriers as they navigate the HIV care continuum. The Women's Health CoOp (WHC), a brief, woman-focused, behavioural, evidence-based intervention, has been shown to be effective in reducing heavy drinking and improving HIV-related outcomes among this key population. However, these women face other broader socioecological barriers to antiretroviral therapy (ART) adherence. METHODS: The WHC was implemented in a modified, stepped-wedge implementation science trial in public health clinics and substance use treatment programmes in Cape Town, South Africa. A qualitative substudy was conducted to explore barriers to HIV treatment adherence among women enrolled in this trial. Eight focus group discussions were conducted with 69 participants 6 months after completion of the WHC workshops. Focus groups were audio-recorded (with consent), transcribed verbatim and analysed using a thematic approach. RESULTS: The mean age of the participants was 33 years and the mean self-reported number of drinks per day was 13. The main contextual factors influencing participants' ART adherence were intrapersonal-level factors (substance use, financial constraints, food insecurity; community-level factors (anticipated and enacted stigma, community violence) and institutional-level factors (patient-provider relationships, health facility barriers, environmental stigma). CONCLUSION: Comprehensive interventions addressing the contextual barriers and unique challenges faced by women who misuse alcohol in low-resource settings that intersect with HIV treatment nonadherence should be implemented in tandem with successful biobehavioural HIV interventions for long-term effectiveness and sustainability. PATIENT OR PUBLIC CONTRIBUTION: Our South African community collaborative board has been involved throughout this study; participants and clinic staff voices have been essential in our interpretation of these findings.

"Because all mothers is not the same": The development and implementation of an in loco parentis informed consent procedure to enroll adolescent girls and young women to participate in HIV research.

INTRODUCTION: South Africa has one of the highest incidences of HIV among adolescent girls and young women (AGW), ages 15-24, and recent research has focused on developing interventions for HIV prevention. However, the South African National Health Act requires those under 18 years of age to obtain a guardian's permission to participate in research. Limiting research enrolment to AGYW who can obtain guardian consent may lead to non-representative findings. Therefore, innovative, inclusive consent approaches that protect AGYW from the risks of research are needed. METHODS: This report details the development and implementation of an approach called the in loco parentis (in place of parent) consent procedure. In loco parentis consent provides a vehicle for adolescent participation that protects adolescents from potential social harms. The in loco parentis consent procedure does not seek to obtain independent minor consent but seeks to obtain permission for the minor to participate in research from a trusted adult who is not a minor's parent or legal guardian. This report also qualitatively explores the experiences of 31 AGYW who were recruited into a behavioral HIV prevention study using this method. RESULTS: Findings suggest that the in loco parentis consent procedure is a feasible and acceptable method to inclusively AGYW in HIV research. CONCLUSIONS: The in loco parentis procedure may provide a more inclusive strategy to recruit AGYW for HIV research to increase the generalizability of findings.

The Association of Recurrent and Multiple Types of Abuse with Adverse Mental Health, Substance Use, and Sexual Health Outcomes among Out-of-School Adolescent Girls and Young Women in Cape Town, South Africa.

Although physical and sexual abuse exposure is a well-established risk for poor health, the dimensions of abuse associated with health among socially vulnerable adolescent girls and young women (AGYW) remain underexamined. This article describes associations between combinations of abuse type and timing with mental health, substance use, and sexual risk outcomes among a sample of 499 AGYW (aged 16 to 19) who had left school early and were recruited for a cluster randomized trial in Cape Town, South Africa. Approximately one-third (33.5%; 95% CI: 28.7, 38.6) of participants reported lifetime abuse. Exposure to more than one type of abuse was associated with increased risk of depression (ß = 3.92; 95% CI: 2.25, 5.59) and anxiety (ß = 3.70; 95% CI: 2.11, 5.28), and greater odds of polydrug use (OR = 2.10; 95% CI: 1.02, 4.34) and substance-impaired sex (OR = 2.17; 95% CI: 1.31, 3.86). Exposure to multiple types of abuse during childhood/early adolescence and again in late adolescence was associated with increased risk of depression (ß = 4.65; 95% CI: 3.15, 6.14), anxiety (ß = 4.35; 95% CI: 2.70, 6.02), and polydrug use (OR = 2.37; 95% CI: 1.03, 5.73). Findings underscore the need for trauma-informed interventions that reduce mental health, substance use, and sexual risks among AGYW who have experienced multiple forms of abuse and recurrent abuse.

Alcohol and Tobacco Use in a Tuberculosis Treatment Cohort during South Africa's COVID-19 Sales Bans: A Case Series.

BACKGROUND: South Africa temporarily banned alcohol and tobacco sales for about 20 weeks during the COVID-19 lockdown. We described changes in alcohol and tobacco consumption after implementation of these restrictions among a small number of participants in a tuberculosis treatment cohort. METHOD: The timeline follow-back procedure and Fägerstrom test for nicotine dependence was used to collect monthly alcohol and tobacco use information. We report changes in heavy drinking days (HDD), average amount of absolute alcohol (AA) consumed per drinking day, and cigarettes smoked daily during the alcohol and tobacco ban compared to use prior to the ban. RESULTS: Of the 61 participants for whom we have pre-ban and within-ban alcohol use information, 17 (27.9%) reported within-ban alcohol use. On average, participants reported one less HDD per fortnight (interquartile range (IQR): -4, 1), but their amount of AA consumed increased by 37.4 g per drinking occasion (IQR: -65.9 g, 71.0 g). Of 53 participants who reported pre-ban tobacco use, 17 (32.1%) stopped smoking during the ban. The number of participants smoking >10 cigarettes per day decreased from 8 to 1. CONCLUSIONS: From these observations, we hypothesize that policies restricting alcohol and tobacco availability seem to enable some individuals to reduce their consumption. However, these appear to have little effect on the volume of AA consumed among individuals with more harmful patterns of drinking in the absence of additional behavior change interventions.

Complete Genome Sequences of Mycobacteriophages Apex and Gophee.

Apex and Gophee are mycobacteriophages directly isolated from soil using the host Mycobacterium smegmatis mc2155. Apex has a 71,244-bp double-stranded DNA (dsDNA) genome encoding 98 putative proteins, and Gophee has a 68,556-bp dsDNA genome encoding 101 putative proteins.

Measuring Relationship Functioning in South African Couples: A Strategy for Improving HIV Prevention Efforts.

Over the past decade there has been increased focus on targeting couples in HIV prevention efforts, particularly in sub-Saharan Africa where HIV transmission primarily occurs through heterosexual contact, in the context of intersecting alcohol use and intimate partner violence (IPV). However, little is known about couples' general relationship functioning. This understanding is needed to augment couple-based HIV prevention programs and address risk for IPV. This paper presents data on domains of relationship functioning with 300 South African couples who were recruited for an HIV prevention study. Exploratory and confirmatory factor analyses were conducted to determine the relevance of 17 individual items, as well as the overall factor structure of the questions. Results revealed three independent factors of relationship functioning: relationship satisfaction, arguing, and open communication; an overarching construct of relationship functioning for these three domains was not observed in the data. Results provide insight into the structure of relationship functioning questions and subscales that can be used to assess South African adult romantic relationships. This may allow for a greater focus on aspects of relationships within couple-based HIV prevention programs going forward.

Genome Sequences of Mycobacteriophages Joselito, Patt, and Tydolla.

Mycobacteriophages Joselito, Patt, and Tydolla were isolated from different soil or water samples using Mycobacterium smegmatis mc2155 as the host. Each was obtained using direct isolation techniques, purified, and then sequenced using the deconvolution of genomes after en masse sequencing (DOGEMS) method.

Acceptability and feasibility of a brief substance use intervention for adolescents in Cape Town, South Africa: A pilot study.

Substance use is prevalent among South African adolescents, but few interventions exist to reduce risk of harm. This study assesses the feasibility, acceptability and preliminary effects of a brief intervention for reducing adolescent substance use and other risk behaviours. This single-arm feasibility test recruited 30 substance-using adolescents and their primary caregiver. Participants received separate interventions (2 sessions for adolescents, 1 session for caregivers), with a subsample randomly selected for post-intervention interviews. Feasibility was measured by the proportion of eligible adolescents who were enrolled and retained in the study. Interviews explored acceptability, and changes in outcomes from baseline to 1-month follow-up assessed preliminary effects of the intervention. Thirty of 43 (69.8%) eligible adolescents and their caregivers were enrolled, with 29 adolescents (96.7%) and 28 caregivers (93.3%) completing the intervention. Twenty-eight adolescents (93.3%) and 29 caregivers (96.7%) were retained at follow-up. Frequency of alcohol, cannabis use and delinquent-type behaviours decreased significantly from baseline to follow-up. Participants appreciated the intervention content and delivery and felt that it facilitated behaviour change. Suggestions for improving the intervention were provided. This study found that the intervention is feasible, acceptable and had promising effects on adolescent behaviour. Efficacy must be established with a randomised controlled trial.

Dihydrocodeine for detoxification and maintenance treatment in individuals with opiate use disorders.

BACKGROUND: Medical treatment and detoxification from opiate disorders includes oral administration of opioid agonists. Dihydrocodeine (DHC) substitution treatment is typically low threshold and therefore has the capacity to reach wider groups of opiate users. Decisions to prescribe DHC to patients with less severe opiate disorders centre on its perceived safety, reduced toxicity, shorter half-life and more rapid onset of action, and potential retention of patients. This review set out to investigate the effects of DHC in comparison to other pharmaceutical opioids and placebos in the detoxification and substitution of individuals with opiate use disorders. OBJECTIVES: To investigate the effectiveness of DHC in reducing illicit opiate use and other health-related outcomes among adults compared to other drugs or placebos used for detoxification or substitution therapy. SEARCH METHODS: In February 2019 we searched Cochrane Drugs and Alcohol's Specialised Register, CENTRAL, PubMed, Embase and Web of Science. We also searched for ongoing and unpublished studies via ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Trialsjournal.com. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. SELECTION CRITERIA: We included randomised controlled trials that evaluated the effect of DHC for detoxification and maintenance substitution therapy for adolescent (aged 15 years and older) and adult illicit opiate users. The primary outcomes were abstinence from illicit opiate use following detoxification or maintenance therapy measured by self-report or urinalysis. The secondary outcomes were treatment retention and other health and behaviour outcomes. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures that are outlined by Cochrane. This includes the GRADE approach to appraise the quality of evidence. MAIN RESULTS: We included three trials (in five articles) with 385 opiate-using participants that measured outcomes at different follow-up periods in this review. Two studies with 150 individuals compared DHC with buprenorphine for detoxification, and one study with 235 participants compared DHC to methadone for maintenance substitution therapy. We downgraded the quality of evidence mainly due to risk of bias and imprecision. For the two studies that compared DHC to buprenorphine, we found low-quality evidence of no significant difference between DHC and buprenorphine for detoxification at six-month follow-up (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.25 to 1.39; P = 0.23) in the meta-analysis for the primary outcome of abstinence from illicit opiates. Similarly, low-quality evidence indicated no difference for treatment retention (RR 1.29, 95% CI 0.99 to 1.68; P = 0.06). In the single trial that compared DHC to methadone for maintenance substitution therapy, the evidence was also of low quality, and there may be no difference in effects between DHC and methadone for reported abstinence from illicit opiates (mean difference (MD) -0.01, 95% CI -0.31 to 0.29). For treatment retention at six months' follow-up in this single trial, the RR calculated with an intention-to-treat analysis also indicated that there may be no difference between DHC and methadone (RR 1.04, 95% CI 0.94 to 1.16). The studies that compared DHC to buprenorphine reported no serious adverse events, while the DHC versus methadone study reported one death due to methadone overdose. AUTHORS' CONCLUSIONS: We found low-quality evidence that DHC may be no more effective than other commonly used pharmacological interventions in reducing illicit opiate use. It is therefore premature to make any conclusive statements about the effectiveness of DHC, and it is suggested that further high-quality studies are conducted, especially in low- to middle-income countries.