Methadone maintenance treatment (MMT) is a convenient, safe and effective substitution therapy for opioid dependence. Experience in the past 30 years has demonstrated that MMT is currently the most effective intervention method for controlling heroin abuse and its related HIV transmission among opioid users. MMT reduces drug injection-related HIV risk behaviours and help drug users to recover their various social functions [1–6].
China is now facing an ever-growing HIV/AIDS epidemic fuelled primarily by intravenous drug use (IDU) . By the end of 2005, IDU accounted for nearly half of new HIV infections . In order to strengthen AIDS prevention and control efforts among intravenous drug users, health advisors to the government strongly advocated a trial MMT programme in China. In February 2003, the Ministry of Health, the Ministry of Public Security and the State Food and Drug Administration jointly issued a Temporary Scheme for Community-based Drug Maintenance Treatment for Heroin Dependents. In August 2003, a national working group, consisting of officials from the Ministry of Health, the Ministry of Public Security and the State Food and Drug Administration and technical experts from the Chinese Center for Disease Control and Prevention (China CDC), Peking University and the Yunnan Institute for Drug Abuse, was established to direct and manage the national MMT programme. The working group has overall responsibility for administration, planning, improvement, monitoring and evaluation, staff training, and oversees the smooth expansion of the programme. At the provincial and county level, working groups have also been established to take on these duties locally. Implementation of the MMT programme was coordinated by a national secretariat, established within the China CDC. A National MMT Training Centre, based in the Yunnan Institute for Drug Abuse, was also established to take responsibility for clinical–technical support and for providing training to healthcare staff working at local MMT clinics.
From March to June 2004, the first eight MMT clinics were established: two in Sichuan, one in Yunnan, two in Guizhou, one in Guangxi and two in Zhejiang, in succession. Eligibility for participating in the first phase of the MMT programme was based on the following five criteria: (i) heroin users who had failed more than one attempt to quit; (ii) at least two terms in a detoxification centre or once in an education-through-labour detoxification facility; (iii) at least 20 years of age; (iv) a local resident and settled in the local area where the clinic was located; and (v) capable of complete civil liability (e.g. of age and sound mind). Heroin users testing HIV positive need only to fulfil requirements (iv) and (v) to qualify. Clients were rejected from the MMT programme if they missed their treatment for a cumulative 15 of 90 days or more than 15 consecutive days. Clients pay no more than 10 Chinese Yuan per day (≈US$1.20) for receiving treatment.
For understanding the safety and effectiveness of the first phase MMT programme, the national secretariat established a tracking system to monitor the on-going processes in each of the eight MMT clinics. This included collection of information from clients upon recruitment and drop-out from the programme. The average daily dosage of methadone given to clients was 44.9 ± 21.9 mg during the first phase.
Given the slow process of recruiting heroin users into the MMT programme and the high drop-out rate from the MMT, three repeated surveys were used for the evaluation. The first survey was conducted between April and August 2004; all clients attending the eight MMT clinics at one month after their entry into the MMT programme were invited to participate in the survey. The second survey was conducted in December 2004 and all clients who had remained in MMT for at least 4 months were invited to participate in the survey. The third survey was conducted from September to November 2005 and all clients who had remained in MMT for at least 12 months were invited to participate in the survey.
All the surveys were conducted by trained local clinical staff and supervised by provincial CDC evaluation specialists. Interviewers were trained in how to administer the informed consent and the questionnaire. Clients who were eligible for the surveys were approached by interviewers and asked if they would be interested in participating in a questionnaire survey. The purpose and nature of the survey was explained and informed consent was obtained. Questionnaires were administered face-to-face in a private room by a same-sex interviewer. Information collected included demographic information, drug use and addiction-related behaviours, drug using-related criminal activities (e.g. stealing, robbery), and employment of the clients. Except for demographic information, all others referenced activity in the month before the date of the survey.
Given high HIV infection rates among drug users, all clients in MMT clinics were encouraged to have a test for HIV one month after entry into the MMT programme. Ten millilitres of blood was taken for HIV antibody testing using enzyme-linked immunosorbent assay (ELISA, Genscreen; Bio-Rad, Hercules, California, USA). Positive test results by ELISA were further confirmed by Western blot (Genelabs HIV Blot 2.2; Genelabs, Singapore). Those who tested HIV negative were subsequently tested again 12 months later to monitor HIV seroconversion rates.
Data management and analysis
All data were double-entered and validated in Epidata 3.0 (EpiData Association, Odense, Denmark). Further data cleaning and data analysis were performed using SAS 9.1 for Windows (SAS Institute Inc., Cary, North Carolina, USA). Continuous variables are reported as mean ± standard deviation, and categorical variables as number and percentage. Pre and posttreatment behaviours of the clients were compared using t-tests for continuous variables and χ2 tests for categorical variables. P values are reported for a two-tailed α < 0.05 level comparing data from the first survey with data collected at the second and third surveys.
Approval to conduct the study was granted by the institutional review board of the National Centre for AIDS/STD Control and Prevention, China CDC.
A total of 585 clients participated in the first survey, 609 in the second survey and 468 in the third survey, with response rates of 96.9, 96.3, 97.4%, respectively. The average age of clients in the three surveys was 32.5 ± 5.4, 33.3 ± 5.9 and 33.0 ± 5.8 years, respectively. There was no statistically significant difference in terms of sex, education, and housing among the three surveys. The proportion of clients from ethnic minorities was, however, lower in the second and third surveys than in the first survey (P = 0.01; Table 1).
Compared with the first survey, the percentage of clients that injected drugs in the past month was significantly lower in the second and third surveys (P < 0.01; Fig. 1). Among IDU clients, the frequency of drug injection reduced from an average of 90 times per month in the first survey to twice per month in the second and third surveys (P < 0.01 for both comparisons).
Clients' societal and familial functions also improved significantly. The number of clients who were employed upon entry to the MMT programme was 22.9%, whereas employment rates were higher in subsequent surveys: 43.2% after 6 months of treatment (P < 0.01) and 40.6% at the third survey (P < 0.01, compared with the baseline survey). Self-reported involvement in drug-related criminal activities (e.g. theft, robbery, drug dealing) among clients reduced from 20.7% before using MMT to 3.6% after using MMT for 6 months, to 3.8% (P < 0.01) after using MMT for 12 months (P < 0.01). The proportion reporting a harmonious relationship with families increased from 49.6% at the entry survey to 65.8% after using MMT for 12 months (P < 0.01), and the proportion reporting a poor family relationship reduced from 14.3 to 1.7% (P < 0.01) (these data were not collected in the second survey). Furthermore, 95.9% of clients reported that they were satisfied with the MMT services and their family members also endorsed the programme.
By the time of conducting the third survey (at 12 months' post-MMT initiation), 3546 clients had been recruited cumulatively into the eight MMT clinics, but 1831 (51.6%) had dropped out. Among those who withdrew, 26.4% had been placed in detention centres by local policemen for continuing use of heroin while receiving MMT, 12.0% left the region, 11.6% were disqualified for not using MMT for 15 days, 5.0% had been arrested for criminal activity, and 30.6% dropped out for unknown reasons.
Data on HIV testing were available for most clients attending MMT, not only those who participated in the surveys. By the time we conducted the third survey, cumulatively 3069 clients had been tested for HIV at entry to the MMT programme, of whom 349 tested HIV positive (11.4%). Among 1153 heroin users who were HIV negative at entry and were retested for HIV 12 months later, eight (0.7%) had seroconverted (Table 2).
An increasing number of countries are adopting MMT programmes to reduce the harmful effects of heroin use. Although MMT programmes operate differently in different countries, their functions generally have the same four goals: (i) reducing heroin usage; (ii) reducing addiction-related HIV risk behaviours, thereby reducing HIV transmission; (iii) reducing addiction-related crimes; and (iv) helping to resume their societal and familial functions [1–4,9–12]. On the basis of the results presented in this analysis, the Chinese MMT programme achieved these goals for those clients who remained in the MMT programme. Information collected from informal talks with local public security staff, relatives of clients and members of the communities where clients lived were consistent with clients' self-reports. As the MMT programme progressed and the number of clients increased, local drug markets began to shrink, crime rates reduced, local public security improved, and individuals increasingly began to understand and support the programme.
One limitation of the study is the selection of participants for the surveys. Patients who had been in and out of treatment or who dropped out completely were not included, and only those clients who had been on methadone continuously for at least 6 and 12 months were included in the second and third surveys, respectively. Those who participated in the survey may be less likely to inject drugs, engage in crimes, have a poor relationship with families and be unemployed, and thus be more likely to adhere to the programme. It is possible that this selection may cause bias that exaggerates the benefits of the MMT programme. Our data suggest that maintenance for long periods has considerable positive benefits; thus we are seeking strategies that increase adherence to the programme. These might include more appropriate (i.e. higher) dosing with methadone, better psychological and community support, and job retraining and placement, discussed below.
Another study limitation is that we had no parallel control group to assess background trends in observed behavioural changes and the incidence of HIV infection. Given the strict enrolment criteria, heroin users participating in the first phase of the MMT programme had failed a few times at trying to stop using drugs; therefore the observed drug-using behaviour changes after participating in the MMT were less likely to be caused by factors other than the MMT. During the same time, two of five MMT sites had community-based observational cohort studies of HIV incidences available that were 3.17% in Sichuan  and 3.1 in Guangxi . These data suggest that the MMT did reduce HIV transmission for those attending the MMT programme.
MMT is a long-term treatment and maintaining the treatment is a challenge. According to work log and field investigations, the main reason for withdrawal was relapse and subsequent internment in compulsory detoxification or rehabilitation through labour. Farre and colleagues  reported that most participants who were dismissed from the MMT had relapsed within one year. Relapse has negative consequences in terms of HIV infection risk, of course. In the study, all eight HIV seroconverter cases had a history of temporary drop-out from the MMT, suggesting that infection may have occurred during relapse. Lower dosages used in the MMT in China compared with what has been deemed optimal in other counties may contribute to the high drop-out rate observed in the Chinese first phase MMT programme. The National MMT Working Group invited several international experts to visit the clinics and provide advice on improvement, and have also encouraged scientific research into retention. Following the experts' advice and some procedural results from the study, a trial has been launched (and is underway as of writing this in October 2007) in some clinics to compare an increased daily dose with the usual dose.
Based on the initial phase of MMT implementation, in July 2006 the National Working Group adjusted the regulations to improve MMT services. In particular, clients are no longer required to be registered as local residents and a transfer system has been set up to meet the needs of those who are relocating either permanently or temporarily. The number of allowable missing treatment days has been relaxed (if an MMT client missed any cumulative 15 days in 90 days they were discharged from the programme, but now they must miss seven consecutive days, a rarer event, to be disqualified). Clients no longer need a history of detoxification for entry into the programme. The programme is to be evaluated as to whether these changes have made any impact on either enrolment or retention.
During the first phase of the MMT programme, psychological counselling, an important component treatment for the quality of services and reasonable retention, were provided only sparingly. This may help explain the high year-one drop-out rate. More comprehensive services are in the process of being added to the standard MMT programme. Additional services include referrals for testing of hepatitis and sexually transmitted infections, health education, group activities, social support, and skills training for employment. HIV-positive clients who were eligible have been enrolled in the government's National Free Antiretroviral Treatment Programme. The clinics also assist HIV-positive clients to access services for the treatment of opportunistic infections and the prevention of mother-to-child transmission of HIV when pregnant.
MMT has become a key component of China's drug control and HIV prevention strategies . Based on preliminary data obtained from the first phase eight clinics, scale up of the programme began in November 2005. By the end of 2006, 320 methadone clinics had been established in 22 provinces, autonomous regions and municipalities, and had provided methadone to 37 345 heroin users. As per China's Action Plan for Reducing and Preventing the Spread of HIV/AIDS (2006–2010), the government of the People's Republic of China intends to expand MMT further.
The authors wish to thank staff at the eight MMT clinics for their help with data collection and Sheena Sullivan for her help with the preparation of this manuscript.
Sponsorship: This study was supported by the Ministry of Health of China. Data analysis and preparation of the manuscript were partly supported by the China Multidisciplinary AIDS Prevention Training Program with NIH Research Grant # U2R TW06918 funded by the Fogarty International Center, National Institute on Drug Abuse, and the National Institute of Mental Health.
Conflicts of interest: None.
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