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Commentary on Zhou et al. (2015): Research on methadone maintenance treatment (MMT) as prevention for HCV infection--MMT is not a single variable.

In this issue, Zhou et al. report on hepatitis C virus (HCV) incidence among 1200 initially HCV seronegative patients entering methadone maintenance treatment (MMT) patients in 20 clinics in Wuhan, China [1]. The cumulative incidence was 34.5/100 person-years (PY) [95% confidence interval (CI) =31.5–36.9/100 PY]. As the authors note, this is a very high HCV incidence. Indeed, this would be a high HCV incidence rate for people who were not in MMT [2]. The primary factors associated with HCV seroconversion were indicators of continued drug injection: self-reported injecting and opiate positive urinalyses. The Zhou et al. study again raises the question of the overall effectiveness of MMT in reducing HCV transmission among people who inject drugs (PWID). MMT is an effective intervention to reduce HIV transmission among PWID, is included in the Joint United Nations Programme on HIV and AIDS (UNAIDS)/World Health Organization (UNAIDS/WHO) list of interventions to prevent HIV infection among PWID [3] and has been recommended as an intervention to reduce HCV infection among PWID [4,5]. The evidence base for recommending MMT for reducing HCV acquisition, however, is not very strong. An international meta-analysis of MMT as HCV prevention identified eight studies with odds ratio (OR) effect sizes ranging from 0.18 to 2.25 (ORs<1.0 indicating protective effects) [5]. The mean weighted protective was not statistically significant (OR=0.6, 95% CI=0.35–1.01). Another, more recent review classified the existing data as having only ‘tentative review level evidence’ [6] for MMT as prevention for HCV. Several new studies in San Francisco, the United Kingdom and Vancouver [7–9] have shown protective effects, but the Wuhan results would balance these in a research synthesis. If, when implemented across a variety of settings, MMT does not consistently reduce acquisition of HCV among PWID, then the chances of controlling HCV transmission in PWID populations would appear to be exceedingly small. There is great variation among MMT programs, and controlling HCV transmission among PWID will require systematic improvement in many MMT programs. There are a number of areas for potential improvement: 1 Eliminate counterproductive program policies and procedures. Many programs have counterproductive policies and procedures, including providing medication at dosages that are too low and discharging patients who continue to use illicit drugs. Inadequate dosages do not suppress injecting opiates and discharging patients who continue to inject is likely to increase their injecting and their risk of acquiringHCV. High threshold MMT entrance requirements—proving failure in drugfree treatment, being a ‘registered’ addict—may also be counterproductive. High threshold entrance requirements will greatly increase the likelihood that a patient will have been exposed to HCV before becoming eligible for MMT. Requiring that all medication be taken at the MMT clinic may also be counterproductive in terms of reducing patients’ ability to be employed and imposing unreasonable travel burdens. The MMT programs in Wuhan require that all patients take all their medication at the clinic. Thus, any patient who does not get to the clinic on a given day is very likely to inject on that day. Providing take-home medication to at least some patients should reduce the number of injections. 2 Identify patients likely to continue injecting while in MMT, and provide additional services to reduce the likelihood of continued injecting. Identifying patients who continue injecting is relatively simple through urinalyses, and there are a number of additional services (cognitive behavioral therapy [10], conditional cash transfers [11]) that could be employed to reduce continued injecting. 3 Utilize MMT programs as platforms for providing HCV testing and treatment. The new direct acting anti-viral treatments offer an opportunity for curing HCV infection and the possibility of ‘treatment as prevention’ for HCV, by reducing the numbers of people capable of transmitting the virus to others. MMT programs could be an important platform for HCV testing, and then either providing HCV treatment on-site or providing supported referrals for off-site treatment of HCV. 4 Coordinate MMT with safer injection programs. Even with improvements in MMT treatment in the above areas, it would still seem unlikely that the improved MMT programs would be able to eliminate continued injecting among all patients. Thus, it will also be necessary to increase the rate of ‘safer’ injecting amongMMT patients who do continue to inject. This will require that eitherMMTprograms provide the needed education and materials for safer injecting or to coordinate with safer injection programs (syringe exchange and pharmacy purchase programs). Zhou et al. note that sterile injecting equipment is available to PWID in Wuhan, but do not describe any efforts by MMT staff to ensure thatMMT patients who continue injecting practice safer