Spatial distribution of HIV, HCV, and co-infections among drug users in the southwestern border areas of China (2004–2014): a cohort study of a national methadone maintenance treatment program

HIV and hepatitis C virus (HCV) infections are major global public health concerns, with overlapping routes of transmission, populations most affected and geographical areas. Data from 2014 suggested that more than 36.9 million people worldwide were living with HIV [1], 115 million people were estimated to be HCV antibody-positive [2], and approximately 2.3 million were estimated to have HIV/HCV co-infection, of whom 59% were people who inject drugs (PWID) [3]. Similar to other oversea countries, China has witnessed the fastest-growing HIV and HCV epidemics fueled by injecting drug users (IDUs) over the past three decades and is experiencing the highest burden of these infections in PWID at present [4‐6]. Methadone maintenance treatment (MMT) programs were first initiated in China as a small pilot project of only eight sites serving 1029 drug users in 2004. Since then, it has rapidly expanded into a nationwide program covering 738 clinics and serving some 344,254 heroin users by the end of 2011, which accounted for approximately 30% of registered IDUs in China [7, 8]. The MMT program in China is believed to have made impressive progress in HIV infection and drug use among PWID [7] as a result of offering various ancillary services, including testing for HIV, syphilis and HCV, psychosocial support, and referrals for the treatment of HIV, tuberculosis and sexually transmitted diseases.

Because it borders the drug-trafficking route known as the ‘Golden Triangle’ and connects China with the Association of Southeast Asian Nations (ASEAN) countries, Guangxi Zhuang Autonomous Region (referred to hereafter as ‘Guangxi’) detected the first outbreak of HIV-1 infection among IDUs in 1996, and transmission through IDUs accounted for 69% of reported HIV cases in 2003, with the second-highest accumulated number of HIV cases in China since 2009 [9‐11]. Guangxi therefore launched an MMT program in 2004 as one of the first eight national MMT pilot clinics [12], covering 72 clinics serving more than 30,000 heroin users by the end of 2014. Numerous studies conducted in China [13‐16] showed that variations toward the prevalence of HIV and HCV infections differed dramatically across geographic locations. Nevertheless, the spatial distribution of these infections among MMT clients in border areas of China, such as Guangxi, is poorly understood, and most previously published studies [17‐19] have concentrated on descriptive analysis. These findings could not visualize the geographic heterogeneity of these infections and detect the presence and location of a cluster in confined regions. We therefore undertook a spatial analysis of the prevalence of HIV and HCV infections among MMT clients from baseline data of treatment between 2004 and 2014, to characterize the geographic distribution patterns and co-clustered epidemic factors of HIV and HCV infections among drug injectors receiving MMT. This study might also have critical implications for policy-making and resource allocation based on the needs of each region, as well as for future MMT program implementation.

To our knowledge, this is the first study to investigate the spatial distribution patterns of HIV and HCV epidemics in relation to MMT clients and their possible interactions in Guangxi. The overall infection rates of HIV, HCV, and HIV/HCV among MMT clients at treatment baseline were 13.05%, 72.51% and 11.96% respectively, which were similar to the rates of high-transmission areas (including Yunnan, Guizhou, Sichuan and Xinjiang) of China, but distinctly higher than those of the other provinces [8]. This finding indicated that the rates of these infections remained highly concentrated among provinces along the traditional drug-trafficking routes, and MMT clinics have recruited more HIV- or HCV-infected drug users as a result of the 2006 national policy to relax the eligibility criteria for MMT enrollment. The similar infection rates of HIV and HIV/HCV suggest that HIV-infected MMT clients were at high risk of co-infected HCV infection. Additionally, this finding showed the important role of IDUs in driving the HCV epidemic among PWID and HIV-infected individuals, which was consistent with previously published evidence [3, 6, 27].

Our study demonstrated that HIV, HCV and co-infections in Guangxi all exhibited significant geographic clustering at the county level, and their distribution patterns overlapped to some degree, particularly for HIV and HIV/HCV co-infection. The most significant high-risk overlapping clusters for these infections surrounded P county in the northeastern area of Guangxi. The overlaps for HIV and co-infections were also located in the area surrounding E and F cities in the southwestern areas of Guangxi, as well as A county. Several important points are considered in interpreting the geographic distribution patterns of these infections. First, E city is adjacent to Vietnam, where the HIV epidemic was driven by IDUs in the early phase and formed the spreading trends from the South to the North since 1990. Guangxi thus first detected a domestic HIV-1 case among IDUs in one county of E city in 1996, which gradually led to an HIV outbreak among drug users in the surrounding border areas [9, 28, 29]. Second, because of its shared border with the ‘Golden Triangle’ and Yunnan province, which were the earliest and most severe HIV/AIDS epidemic areas in China, F city became one of the most severely affected HIV/AIDS areas initially fueled by IDUs in Guangxi [30]. Third, as previous studies have shown, the geographic concentrations of HIV in poor and underserved areas and the dispersion of HIV along roads and highways [31‐34] are high, and it is indeed the case that most of the locations surrounding P county, including E and F cities, belong to economically depressed areas. These findings corroborated that HIV and HCV epidemics first broke out within the border areas adjacent to the ‘Golden Triangle’ and then along drug trafficking routes to other parts of Guangxi, and poverty might play an important role in accelerating these epidemics. Meanwhile, the most significant low-risk overlapping clusters for HIV, HCV or co-infections were mainly located in areas surrounding H and J cities or I county, which was consistent with the trend from routine monitoring data of Guangxi. This information suggested that some behavioral or biological protective factors appear to have slowed the transmission of these infections in the low-risk clusters.

The distribution patterns of HIV, HCV and co-infections are similar to those across different counties, which might be attributed to the similarities in the features of the epidemics. Compared with related studies [35‐37], our findings showed that several epidemic factors, such as being unmarried, having a primary level of education or below, having used drugs for more than 10 years and receptive sharing of syringes with others, were geographically clustered. Most of the individuals with these factors were more likely to reside in one of clusters for HIV, HCV and co-infections, especially for the high-risk clusters (e.g., the areas surrounding P county as the cluster center). Numerous studies have reported that the emergence of MMT and other harm reduction programs have resulted in lower levels of risky behaviors and reductions in the HIV epidemic [7, 12, 38, 39]. However, not all previous studies have found such a tight linkage, as one study from the San Francisco Bay Area [40] found that risky injection practices were indeed lower among drug users from poorer communities targeting harm reduction programs, but the prevalence of HIV remained high. Therefore, additional studies should be conducted to evaluate the spatial distribution of these infections and their association with epidemic features after MMT programs have been more widely established.

The similar prevalence and overlapping spatial clusters found in our study between HIV and HIV/HCV co-infection suggest a higher prevalence of HCV co-infection among HIV-infected PWID in Guangxi. Co-infection of HIV and HCV interact synergistically by affecting the transmission history and reducing the immune clearance of the other. Individuals co-infected with HCV could boost the occurrence of HIV infection, with the perinatal transmission risk doubling in HIV-infected mothers [41, 42], thus altering immunological responses to antiretroviral therapy and accelerating the risk of drug-related hepatotoxicity and consequently cirrhosis, liver failure, and hepatocellular carcinoma [43‐45]. Meanwhile, HIV-infected individuals without treatment are less likely to spontaneously clear HCV infection; they may then experience more rapid HCV disease progression than HIV-negative individuals [3, 46]. Given the fact that a large proportion of HIV cases are acquired through IDUs in Guangxi, there is an urgent need to comply with international guidelines that recommend HCV screening for HIV-infected individuals, investment in building HCV surveillance and care, and access to direct-acting antiviral treatment for those with chronic active infection [47‐50]. Comprehensive measures in parallel to MMT, such as antiretroviral therapy, 100% use of condoms, needle exchanges and sexually transmitted disease management services should be promoted as well.

Several limitations in this study should be noted. First, it is difficult to determine whether the distribution patterns and associations of the MMT clients described in this report are true for the entire population of injectors in this region. However, one study reported by national sentinel surveillance has shown that the national HIV prevalence among MMT clients was not significantly different from that of non-MMT drug users from 2004 to 2009 [8]. Second, most of the data included were obtained from 2008 to 2014, given that a national MMT program database was developed in 2004 to monitor the pilot and was later upgraded to a web-based management database in 2008. Third, most of the data, including residential addresses and drug use behaviors, were self-reported, and we have no way knowing the proportion of the clients giving false or misleading information. Nevertheless, the information bias might be narrowed given that the staff members of local MMT clinics needed to receive a series of professional trainings on assessment surveys, after which they could upload clients’ information to the national web-based management database prior to their assignment. Most of the clients were later contacted at the addresses they provided as well. Finally, MMT clients without a fixed address (and who were thus more likely to be at high risk) were excluded, and drug use is likely to occur in venues or areas of the city that might not coincide with an address. Therefore, the location of consumption would have been a better approach for the analysis.

Using spatial analysis for detecting the HIV and HCV epidemics among drug users from a cohort study of MMT programs from 2004 to 2014, we revealed two important findings. First, HIV, HCV and co-infections among MMT clients in Guangxi Zhuang Autonomous Region all presented substantial geographic heterogeneity at the county level with a number of overlapping significant clusters. Second, areas surrounding P county were effective in enrolling high-risk clients in their MMT programs, which in turn might allow PWID to inject less, share fewer syringes, and receive referrals for HIV or HCV treatment in a timely manner.