Sexually Transmitted Diseases:
Evaluation of Harm Reduction Programs on Seroincidence of HIV, Hepatitis B and C, and Syphilis Among Intravenous Drug Users in Southwest China
Ruan, Yuhua PhD*; Liang, Shu MD†; Zhu, Junling MD*; Li, Xudong MD*‡; Pan, Stephen W. MS§; Liu, Qianping MD¶; Song, Benli MD¶; Wang, Qixing MD∥; Xing, Hui MS*; Shao, Yiming MD, PhD*
From the *State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; †Sichuan Provincial Center for Disease Control and Prevention, Chengdu, Sichuan, China; ‡Tianjin Hangu Center for Disease Control and Prevention, Tianjin, China; §The School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; ¶Xichang Center for STD and Leprosy Control, Xichang City, Sichuan, China; and ∥Liangshan Prefecture Center for Disease Control and Prevention, Xichang, Sichuan Province, China
Author’s contributions and approval of text: Study design: Yuhua Ruan and Yiming Shao. Data collection: Shu Liang, Junling Zhu, Xudong Li, Qianping liu, Benli Song, and Qixing Wang. Data analysis: Yuhua Ruan and Xudong Li. Data interpretation and writing: Yuhua Ruan, Stephen W. Pan, Hui Xing, and Yiming Shao. Principal investigator: Yiming Shao.
All authors have read and approved the text as submitted to the journal.
Supported by grants from the National Natural Science Foundation of China (81273188), the Ministry of Science and Technology of China (2012ZX10001-002), and Chinese State Key Laboratory for Infectious Disease Develop Grant (2012SKLID103).
Conflicts of interest: None.
Correspondence: Yiming Shao, MD, PhD, State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China, 155 Changbai Rd, Changping District, Beijing 102206, PR China. E-mail: firstname.lastname@example.org.
Received for publication July 16, 2012, and accepted November 21, 2012.
Objective: The aim of this study was to evaluate the impact of a multifaceted harm reduction program by comparing seroincidence rates of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and syphilis before and after implementation of harm reduction strategies among intravenous drug users (IDUs) in a drug-trafficking city in Southwest China.
Design: This is a prospective cohort study with 24 months of follow-up.
Methods: Two prospective cohorts (cohort 2002–2004 and cohort 2006–2008) were followed up every 6 months for seroconversions of HIV, HCV, and syphilis antibodies and HBV surface antigen.
Results: After implementation of harm reduction strategies in Xichang city, Sichuan province, the HIV incidence rate among IDUs significantly dropped from 2.5 to 0.6 cases per 100 person-years. Subanalyses also indicated that the incidence rate of HBV significantly declined from 14.2 to 8.8 cases per 100 person-years. No significant changes in the seroincidence rates of HCV or syphilis were detected after implementation of IDU harm reduction strategies.
Conclusions: Harm reduction strategies may help reduce the high incidence of certain blood-borne infectious diseases and sexual transmitted diseases among high-risk IDUs in southwest China. Additional research is needed on the implementation and evaluation of harm reduction strategies in China.
In the 1980s, China adopted an open-door economic policy that was quickly followed by a reemergence of global drug trafficking, abuse, and addiction.1,2 The number of drug users registered by Chinese public security departments rose from 70,000 in 1990 to 1.22 million in 2009 at an average annual increase of 12%.3 However, the current estimated number of drug users is 3 to 8 times that number.4 The main drug of choice in China is heroin. According to a report of the National Narcotic Control Commission, 87.6% of drug users abused heroin,4 most of whom were young people with low education levels and limited job skills in rural southwest China.5,6 High prevalence of drug use in southwest China is largely caused by its close proximity to the world’s major heroin producing area known as the Golden Triangle, where most of heroin in China’s market is brought from Myanmar (also known as Burma) into Yunnan province or from Viet Nam into Guangxi province. From there, heroin shipments follow the “Golden Crescent” drug-trafficking routes to the southwestern and western Chinese provinces of Sichuan, Guizhou, and Xinjiang.
The spread of HIV in China has been predominantly fueled by intravenous drug users (IDUs).5,6 The first reported case of an HIV-infected IDU in China was reported in the southwestern province of Yunnan along the border with Myanmar in 1989.7 By 2002, HIV infection among IDUs had been reported in all 31 mainland provinces, and 71% of infections in China were estimated to be caused by intravenous drug use.8,9 However, HIV prevalence among IDUs has generally been higher in southwestern and western provinces that lie along major drug-trafficking routes. HIV prevalence among IDU surveillance sites has exceeded 20% in the southwestern and western provinces of Yunnan, Xinjiang, Sichuan, and Guangxi10–13 but has remained below 10% in the eastern coastal provinces of Shandong, Jiangsu, and Zhejiang.9 By the end of 2005, the China Ministry of Health estimated that IDU-related transmission accounted for 44.3% of HIV infections, followed by heterosexual transmission (19.6%).14 Meanwhile, high infection rates of syphilis, hepatitis C virus (HCV), and hepatitis B virus (HBV) were also found among Chinese IDUs.
In response to the growing burden of HIV and heroin addiction, harm reduction programs such as methadone maintenance therapy (MMT), needle exchange, and condom promotion were implemented at the national and local levels in 2004.15–18 Due in part to the relatively strong effectiveness of interventions that target IDU, the HIV epidemic in China, similar to other Asian countries, has shifted from a predominantly drug-driven to sexually driven epidemic. Based on a joint assessment by the Chinese Ministry of Health, Joint United Nations Programme on HIV/AIDS, and World Health Organization of China’s 780,000 people living with HIV/AIDS at the end of 2011, 46.5% were infected through heterosexual transmission and 28.4% through drug injection.19 However, there have been few studies that assess trends of seroincidences of HIV, HCV, HBV, and syphilis among IDUs before and after relevant harm reduction strategies were implemented. Moreover, such studies have only assessed single-component interventions, whereby harm reduction programs may include MMT and/or needle exchange but no condom promotion component. Multifaceted harm reduction programs may help further reduce the spread of HIV and other infections among IDU. The goal of the present study is to evaluate the impact of a multifaceted harm reduction program by comparing seroincidence rates of HIV, HCV, HBV, and syphilis before and after implementation of the program.
This study was conducted in Xichang city of Sichuan province in southwestern China, which is located along one of China’s major drug-trafficking routes. The city hosts a population of more than 600,000, with most ethnically Han people. Approximately 10% of the population is of minority Yi ethnicity. Xichang City has approximately 100,000 incoming migrant people each year and nearly 2500 registered drug users and 2800 female sex workers. In 2004, Xichang city began the implementation of the following harm reduction programs as part of a new national HIV prevention strategy: MMT, a needle-exchange program, addictions counseling, and condom promotion.15–18 Methadone maintenance therapy services were provided at one clinic administered by the Xichang Center for STD and Leprosy Control. Clients on MMT were referred by drug detoxification centers and were required to appear in person to collect their daily dose of methadone. The maximum cost of one daily dose of methadone was set at 10 CNY (∼1.20 US dollars). Needle exchange, addictions counseling, and condom promotion were administered by local health care providers.20 Condom promotion entailed the provision of free condoms and educational materials at health care provider clinics. Throughout the intervention period, 3 to 5 peer drug users conducted community-based outreach to promote needle-exchange services. Methadone maintenance therapy services provided by the Xichang Center for STD and Leprosy Control operated independently of harm reduction services provided by local health care providers.
Study Design and Study Population
Participants of 2 prospective cohorts (cohort 2002–2004 and cohort 2006–2008) were enrolled in November 2002 and from March 2006 to June 2006, respectively. The 2002–2004 cohort represented IDUs preintervention and the 2006–2008 cohort represented IDUs postintervention. Study participants were recruited through community-based outreach and snowball sampling. Outreach workers distributed information about the study throughout the local community and directly contacted known IDUs. Other participants were recruited by word of mouth. Participant eligibility criteria at baseline included 18 years or older and injected drugs at least once in the last 3 months. Those who were HIV seropositive for the baseline prescreening HIV enzyme-linked immunosorbent assay (ELISA) test were excluded from the study. Participants were asked to come back to the study clinic for follow-up evaluations every 6 months for a maximum of 24 months. Annual retention rates were assessed at the 12th and 24th months of follow-up. Additional details of the study protocol and cohort retention have been described elsewhere.10,13 The study protocol was approved by the institutional review board of the Chinese Center for AIDS/STD Control and Prevention, and written informed consent was obtained from all participants before enrollment.
Each study participant was assigned a unique identifier code to keep all collected data confidential. An interviewer-administrated questionnaire was used to collect data on demographic characteristics and information concerning drug injection practices (e.g., frequency of injection and syringe sharing experience), unprotected sex with primary and nonprimary sex partners, buying and selling sex, new sex partners, and use of MMT and needle exchange.15–18 Participants were asked to come back to the study clinic for follow-up evaluations every 6 months. The questionnaire had been previously tested in China and was modified based on another international cohort study—the HIV Prevention Trials Network Preparedness Study 033.11,12
A blood sample was collected from each participant for testing HIV, HCV, and syphilis antibodies, and hepatitis B surface antigen every 6 months at follow-up. HIV infection status was determined by an enzyme immunoassay (Beijing Wantai Biological Medicine Company, Beijing, China) and an HIV-1/2 Western blot confirmation (HIV Blot 2.2 WB; Genelabs Diagnostics). Samples were tested for antibodies to HCV by ELISA (Beijing Jinhao Biological Production Company, Beijing, China). Hepatitis B surface antigen was tested using an HBV ELISA (Beijing Wantai Biological Medicine Company). Syphilis infection was determined using an enzyme immunoassay (Beijing Jinhao Biological Production Company) and confirmed using a Treponema pallidum particle agglutination test for detection of antibodies to T. pallidum (FUJIREBIO, Tokyo, Japan).
Questionnaire data were double data entered and validated with EpiData software (EpiData 3.0 for Windows; The EpiData Association, Odense, Denmark). After cleaning, the data were then converted and analyzed using Statistical Analysis System (SAS 9.1 for Windows; SAS Institute Inc, Cary, NC, USA). Univariate proportions and means were calculated for categorical and continuous variables, respectively. To assess differences between the 2002–2004 and 2006–2008 cohorts at baseline, χ2 tests and t tests were used for categorical and continuous variables, respectively.
The seroincidence density rates were calculated based on Poisson distributions and as cases per 100 person-years of follow-up. Dates of seroconversion were estimated using the midpoint between the last negative and the first positive antibody test result. Multivariate Poisson regression models were used to compare seroincidence rates of HIV, HCV, HBV, and syphilis for 24 months of follow-up in cohort 2002–2004 and cohort 2006–2008. Because some participants of the 2002–2004 cohort accessed MMT soon after it was offered in 2004, a separate 12-month subgroup analysis restricted to the years 2002–2003 that predated MMT services was also performed.
In the 2002–2004 cohort, a total of 382 IDUs were screened: 2 persons did not meet eligibility criteria, 4 refused to participate, and 43 were HIV seropositive and therefore excluded. In the 2006–2008 cohort, a total of 430 IDUs were screened: 2 persons did not meet eligibility criteria, 1 refused to participate, and 51 were HIV seropositive and therefore excluded. A total of 333 and 376 HIV-seronegative eligible IDUs were recruited into cohort 2002–2004 and cohort 2006–2008, respectively. The follow-up retention rates at 12 and 24 months were 70.3% and 75.7% for cohort 2002–2004 and 89.4% and 83.8% for cohort 2006–2008, respectively (Table 1). Study participants recruited in 2006 were significantly older than those recruited in 2002, with a mean difference of 4 years; ethnic Han participants constituted a significantly larger proportion of the 2006–2008 cohort; the proportion of those with more than 6 years of education was significantly higher in the 2006–2008 cohort; the mean annual personal income was significantly higher in the 2006–2008 cohort; the proportion of participants using heroin and sharing needles in the last 3 months was significantly lower for the 2006–2008 cohort. The following variables were comparable and not significantly different between the 2002–2004 and 2006–2008 cohorts: sex, current employment, marital status, and owning a house or apartment. There was no significant difference in the prevalence of high-risk sexual behaviors between the 2002–2004 and 2006–2008 cohorts.
Seroincidence of HIV, Hepatitis B and C, and Syphilis
A statistically significant difference in HIV seroincidence was detected between cohort 2002–2004 and cohort 2006–2008. Twelve and 4 HIV seroconversions were observed for 473.5 and 642.6 person-years of observation, corresponding to incidence density rates of 2.5 per 100 person-years (95% confidence interval [CI], 1.1–4.0) and 0.6 per 100 person-years (95% CI, 0.01–1.2) during the 2 years of follow-up in cohort 2002–2004 and cohort 2006–2008, respectively (Table 2).
Seroincidence during 2 years of follow-up in cohorts 2002–2004 and 2006–2008 was 38.5 and 30.3 per 100 person-years for HCV, 12.0 and 8.8 per 100 person-years for HBV, and 4.7 and 4.1 per 100 person-years for syphilis, respectively. However, no significant changes of those seroincidence density rates were detected (Table 2).
After restricting the 2002–2004 cohort to the years 2002 to 2003, both HIV and HBV incidence density rates were significantly higher than that of the 2006–2008 cohort. However, no significant differences for HCV or syphilis were found (Table 2).
Harm reduction programs have been implemented in China since 2004,15–18 but there have been few data on seroincidences of HIV, HCV, HBV, and syphilis among IDUs before and after implementation of harm reduction programs. Our findings indicated that the HIV incidence rate among Xichang IDUs after implementation of harm reduction strategies was less than 1 per 100 person-years, significantly lower than HIV incidence rates before introduction of harm reduction services in Xichang, and lower than rates in Xinjiang and Guangxi provinces, as well. From 2002 to 2003, studies among 508 and 500 IDUs in Xinjiang and Guangxi provinces showed HIV-1 incidence rates of 8.8 per 100 person-years (95% CI, 6.3–12.0) and 3.1 per 100 person-years (95% CI, 1.6–5.2), respectively.11,12 Subcohort analyses also indicated that HBV incidence significantly declined after the implementation of harm reduction interventions. Significantly lower baseline prevalence of needle sharing in 2006 compared with 2002 suggests a possible mechanism by which harm reduction programs may have impacted HIV and HBV incidence density rates, although the temporal decline in needle sharing may also have been caused by other factors such as ethnicity. Our previous study suggests that ethnic Yi IDUs may be more likely to share needles than ethnic Han IDUs, although no ethnic differences were detected regarding sexual behaviors.10 Hence, part of the temporal decline in needle sharing may be attributed to the greater proportion of ethnic Han participants in the 2006–2008 cohort and lower prevalence of needle sharing among ethnic Han IDUs.
Seroincidence for HCV was very high from 2006 to 2008 in the years after the implementation of harm reduction programs (30.3 per 100 person-years) and not significantly different from the years immediately preceding introduction of harm reduction services. Although the persistently high incidence of HCV may partially be attributed to harm reduction programs with less than ideal efficacy, low participation in needle exchange (∼9%) and MMT (∼30%) strongly suggests that low coverage rather than inherent programmatic flaws may have been the preponderant reason why HCV incidence did not significantly decline after harm reduction services were introduced. To optimize program effectiveness, future studies should investigate reasons for the low uptake of needle exchange and MMT among Chinese IDUs. In addition, HIV and HBV incidence alone may not be a sufficient indicator for evaluating the effectiveness of harm reduction programs because HCV infections are found to be very high among Chinese IDUs.20–22
This is also the first study in China to evaluate syphilis seroincidence in a prospective cohort study of IDUs. Among Xichang IDUs, seroincidence of syphilis infection was high both before and after implementation of IDU harm reduction programs, and no significant changes over time were detected. This is further echoed by the relatively high and unchanged prevalence of unprotected sex after harm reduction interventions were introduced. The high syphilis incidence rate suggests that large numbers of IDUs engaged in risky sexual practices and may have transmitted HIV/sexually transmitted diseases (STD) to others. Ulcerative STDs like syphilis are of particular concern because they have been found to increase the likelihood of HIV seroconversion by 2 to 5 times.23–25 Comprehensive prevention programs should consider simultaneously addressing risks of both drug use and sexual behavior.
Although it is generally believed that IDUs are difficult to retain in a prospective cohort study, we observed a relatively high retention rate among IDUs in Xichang city. This may have been partly because of retention strategies designed to increase the follow-up retention rate and minimize potential selection bias. For example, all participants were asked to provide at least 2 different means of contacting them. Study staff then reminded participants of their follow-up appointments 2 to 3 weeks in advance of the appointment date and would make personal home and street visits if necessary. Additional details about the cohort retention plan have been described elsewhere.10 The retention rate after 24 months of follow-up was 75.7% in cohort 2002–2004 and increased to 83.8% in cohort 2006–2008 (P < 0.01). Based on our previous study, we found that ethnicity and appearing at the 6-month follow-up visit were associated with retention at 12 months.10 Despite efforts to maximize retention, 81 and 61 participants were still lost to follow-up in cohorts 2002–2004 and 2006–2008, respectively. Reasons for loss to follow-up among the 2002–2004 and 2006–2008 cohorts included death (38.2% and 21.3%), moving out of the area (28.9% and 34.4%), wrong contact information (18.5% and 27.9%), and in jail or detoxification because of drug use (6.0% and 3.3%). Among those who died during the study period, 71% and 38% of deaths were attributed to illicit drug overdose in cohorts 2002–2004 and 2006–2008, respectively.
Findings from this study should be interpreted in light of several limitations. First, insufficient statistical power because of small sample sizes may have precluded detection of significant changes in HCV and syphilis incidence density rates over time. Second, although controlled for in multivariate modeling, differences in ethnicity, education, and income between the 2002–2004 and 2006–2008 cohorts suggested the possibility of selection bias that may have led to overestimation of the intervention’s true impact. Third, there was insufficient data about how intensely and consistently participants used harm reduction services throughout the postintervention study period. Moreover, low uptake of MMT and needle-exchange services may have led to an underestimation of the intervention’s true potential measure of effect. Fourth, temporal community-level changes in access to drugs, HIV knowledge or education, and illicit drug enforcement practices may also have impacted seroincidence rates before and after harm reduction interventions were introduced. Fifth, given that 17% of participants in the 2002–2004 cohort accessed MMT services in 2004, exposure misclassification bias in the 2002–2004 cohort may have attenuated the intervention’s true measure of effect for comparisons between the 2002–2004 and 2006–2008 cohorts. Sixth, exclusive reliance upon treponemal diagnostic tests may have biased the incidence and prevalence rates for syphilis. Individuals who recovered from historical treated syphilis would have likely tested positive for syphilis at baseline and therefore been inadvertently excluded from the syphilis incidence rate calculation. Assuming that rates of incident syphilis infection are higher among those who have been previously infected, this may have led to an underestimation of the true syphilis incidence rate. Also, baseline prevalence of syphilis infection may have been inflated because the treponemal tests administered at baseline screening did not distinguish between those with current untreated syphilis and those who recovered from historical treated syphilis. In the absence of clinical examinations, the treponemal tests also may not have been able to detect early cases of primary syphilis. Finally, because reasons for loss to follow-up varied slightly between the 2002–2004 and 2006–2008 cohorts, incidence rate comparisons should be interpreted with caution.26,27
Data from this study demonstrate that harm reduction strategies may be an effective means of reducing the spread of certain blood-borne infectious diseases and STDs among high-risk IDUs in southwest China. However, most study participants were unaware of, unwilling to use, or unable to access current harm reduction services. Considering its wide geographic variability, China requires additional scientific data for understanding how harm reduction programs can be successfully implemented to reduce transmission of HIV, HCV, HBV, and syphilis. This study underscores the need for academic, government, and community organizations to urgently mobilize and address the serious public health issues related to IDUs in China.
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