This month the American Journal of Public Health published an article with surprising new findings: People who inject prescription opioid analgesics (pain pills) are five times more likely to be hepatitis C infected than people who inject other drugs like heroin or cocaine.

The study also reports that people who share injection equipment, such as cookers, cottons and water are four times more likely to be infected with hepatitis C than people who do not share injection equipment. Last week I spoke with Jon Zibbell, researcher with the Division of Viral Hepatitis at the Centers for Disease Control and lead author on the report, to ask about the science behind these extraordinary findings.



TC: Why would injecting prescription opioids tablets put people at greater risk for hepatitis C than injecting heroin or other drugs?

JZ: That is the million dollar question. Unfortunately, we don't know for sure, meaning there are no agreed-upon reasons in the literature, but I have a few hypotheses. One possibility is that when people crush pills and add water, the inert ingredients absorb most of the added water, leaving almost no available solution to draw into the syringe. So folks often add more and more water to the mix until a viable solution is created, one that's able to be drawn into a syringe. But sometimes, and particularly with abuse-deterrent formulas that are designed to gel in the presence of water, the inert ingredients absorb so much water that the amount required to make an expedient solution produces a volume much too large to be held by the 1/2 cc or 1 cc insulin syringes, the type used by most PWID in the U.S. When this happens, people have a couple of options. If the solution is, let's say, 3ml, then they can either perform three, distinct injections with a 1cc syringe if they desire to use the whole solution in one sitting, meaning during one injection episode. Or if they want to inject the entire solution in one shot, then they will need to use a syringe with a larger barrel, such as a 3ml syringe, which has a detachable needle and a higher dead-space. But either way they are at increased risk.

Performing multiple injections: The evidence is clear that the more times a person injects per day, the more at-risk they are for acquiring blood-borne infections. For example, if a person needs to inject three times during a single injection episode to use up their entire tablet solution, and they regularly perform three injections every time they inject a pill solution, then the total number of times per day they inject increases three-fold when injecting prescription opioids relative to injecting heroin or other drugs. This is what increases their level of risk three-fold.

Using high dead space syringes (HDSS): A recent study by Dr. Bill Zule has identified increased risk for HCV infection associated with the use of high dead space syringes (HDSS) because HDSS can retain 40 times more contaminated material post-injection -- meaning after the plunger is fully depressed -- than low dead-space, or insulin syringes. The larger volume of contaminated material remaining in the syringe after the plunger is fully depressed means that more contaminated blood is able to remain in the syringe post-injection. And with more contaminated blood remaining in the syringe, the more virus is able to be transferred to another person when the syringe is shared.

And lastly, it may also have to do with the fact that it takes longer to prepare and inject prescription opioids than it does with heroin. Greg Scott from DePaul University has shown that the longer an injection episode takes to occur -- from the time a person sets up their equipment on a surface to the time they inject -- the greater the risk of infection, since there are more opportunities with a longer episode for injection equipment to be contaminated. And since preparing and injecting POs often require a longer duration of preparation time, then perhaps this is placing PO injectors at increased risk for HCV. Either way, Greg's findings run contrary to previous understandings of the association between length of injection episode and infection risk, where it was thought that a person was at increased risk for acquiring a blood borne virus when they rushed through their set-up and injection, such as when someone is dope sick; the logic being that PWID do not care about hygiene or risk while injecting drugs while in a state of withdrawal. Greg's work is of critical importance because it shows the opposite to be true.

There are all hypotheses, however. The literature has not yet provided answers. In an attempt to answer these questions, we have a survey investigation underway in rural Wisconsin meant to investigate the link between drug injecting behaviors and HCV infection status. I'm hopeful that we can soon shine some light on these pressing questions.

TC: What do the results of this study mean for hepatitis C prevention and safer injection habits?

JZ: The most important thing is to provide access to sterile injection equipment (both needles and prep equipment) to persons unwilling or unable to stop injecting so they do not have to re-use contaminated equipment, which is proven to occur when said equipment is scarce. But secondly, and equally important, is the need to educate people about the hazards of sharing preparation equipment in addition to needles/syringes. Programs often discuss the importance of not sharing needles/syringes with their participants, but they also need to talk to them about not sharing preparation equipment, meaning cookers, cottons and water (and even surfaces, tourniquets, alcohol swabs, etc.). For example, in our study in upstate NY, 40 percent of persons who were HCV [hepatitis C] positive reported sharing syringes while 80 percent report sharing preparation equipment. We also discovered that person who report sharing preparation equipment were roughly 4 times more likely to be HCV infected. This is cause for great concern, and may be why SEPs have had a more difficult time reducing HCV incidence than they have reducing HIV transmission, i.e. because HCV may be more transmissible on prep equipment than HIV.

As concerns safer injection, we are finding that safer injection techniques have been designed based on the risk posed by HIV, but we now know that HCV acts differently. HCV has been shown to survive outside the body and on inanimate objects for longer periods of time than HIV. So we need to reconfigure our safer injection protocols in aligned with the risk associated with HCV.

But there are also geographic limitations with regard to safer injection knowledge. Many urban areas, like NYC, Chicago or SF, have numerous SEPs and these programs have been very effective in distributing information with respect to safer injection. But rural areas are a different story. Contrary to the 1980s and 90s, when the majority of HCV infections were occurring in urban areas, the recent increase in acute HCV cases are occurring in nonurban areas, and mainly in the Appalachia region. These locales have no syringe exchange, no pharmacy access, and a lack of drug treatment programs, which makes the delivery of safer injection information to PWID nearly impossible. We need to use our experience with risk reduction in urban areas to inform programmatic interventions in rural areas. The most important things for rural locales is to increase access to sterile injection equipment, safer injection education, drug treatment, HCV testing initiatives, and linkage to HCV care and treatment for those infected.

And prescription opioids are, for the most part, a rural epidemic. In Kentucky, West Virginia and Tennessee, for example, the majority of PWID are recent initiates to injecting (

To address the HCV epidemic in these areas, the CDC has two demo projects. One is in New Mexico and the other is in Cincinnati. From these projects we will try to understand HCV transmission patterns among young PWID and their injecting networks to inform the development of prevention interventions that are specific to rural America. Given the difficulty reaching PWID when they are not using services, and especially young persons, our hope is that these projects will show us a way to reach young PWID while also providing an understanding of their drug use patterns so we can tailor prevention messages and treatment access in alignment with geography, age, race, drug use, etc. And this certainly rings true when designing prevention programs and treatment strategies for PWID. One size surely doesn't fit all.

TC: What are your current projects?

JZ: Besides the prevention research mentioned above, we are working to make the change from interferon-based HCV therapy to oral therapy benefit former and active drug injectors. Many HCV-infected PWID have fear around taking interferon, but the new all oral, non-IFN based drugs that are available now, albeit at an exceedingly high cost, are a game changer. We are deliberating on the potential to treat active injectors who are HCV-infected as a way to prevent future transmissions. What I mean is that, say we have a prevalence rate of 80 percent among PWID in New York City, and we can reduce that prevalence to 30 percent through targeted treatment, perhaps we can reduce the chance of injecting with an infected person by 50 percent. In other words, if we can reduce the cost of treatment and be able to treat active injectors then perhaps we can look at treatment as another tool in our prevention toolbox, especially with newly infected people where the level of transmission is greatest.