A Thousand Picks & Hammers: Eliminating Hep C by Sheer Determination
Some Last Words on the 11th Australasian Viral Hepatitis Conference
I’ve mentioned that the big Hep C drug companies contributed significantly to the conference, both financially and with a considerable physical presence. Their pavilions were neon-suffused, architect-designed chill-out spaces stocked with sci-fi coffee machines and staffed by razor-suited reps with sharp, on-message responses to every query – and a certain snarkiness when it came to their big pharma neighbours.
(Before I get too far, I should correct myself. In a previous post – one of the newsy ones – I mentioned that Merck & Co was ducking out of the Hep C market after the failure of one of their experimental drug combinations. Merck & Co is known as MSD (Merck Sharp & Dohme) in Australia and, contrary to my prior understanding, they remain in the Hep C game with their DAA (Direct Acting Antiviral) combo Zepatier, which has certain niche applications among patients with genotype four and/or kidney issues.)
I asked the MSD people about Zepatier’s relevance in the age of big pangenotypics like Gilead Science's Epclusa and - particularly - AbbVie’snew blockbuster Mavyret. I was swiftly and eagerly appraised of Mavyret’s failings. These included an improbably long list of drugs with which it cannot be combined: several HIV meds, some statins, and Seroquel (all medicines which Hep C treatment candidates might conceivably be using).
Later, I did a fact check. Some HIV meds, some antibiotics and St. John’s Wort are indeed contraindicated for use with Mavyret, but nothing else, or at least nothing I could find from an apparently trustworthy source. I don’t know exactly how hard these drug reps go at each other, whether they’d resort to slander, but maybe do a little fact checking of your own, in collaboration with your prescriber, whatever you’re prescribed. (And don’t, for heaven’s sake, read this as criticism of what, in Mavyret, may be the best Hep C combo thus far.) (Guest Speaker Dr. Sunil Solomon also happened to mention, in passing, a few adverse DAA interactions - mainly the HIV meds and by no means restricted to Mavyret - but more of Dr. Sunil soon.)
During this research, I encountered something of a factoid which, for all my browsing on the subject of Hep C, I've never before noticed. It concerns Hep C patients who are co-infected with Hep B and the faint possibility that treatment with DAAs may reactivate that virus, even if dormant. I found packet warnings encouraging health care professionals to ‘screen patients for evidence of current or prior HBV infection before starting treatment.’
It turns out that such screenings have, since 2016, been a part of general practice in Australia. Because I was so quick out of the gate treatment-wise, I probably missed this, but don’t worry too much. In fact, don’t worry at all. The warning is less a warning than a covering of the arse and is based on tens of cases among tens of thousands. Absolutely, do not let it deter you from treatment.
There are 350 million people in the world with Hep C compared to 33 million with HIV. That's more than ten times as many people with Hep C than HIV - yet those with HIV enjoy the fruits of a planetary network of support and advocacy, while those with Hep C… well, not so much.
The aforementioned Dr Sunil Solomon lamented this lack of funding and political will which is letting down the sufferers of Hep C. He asked if the extraordinary, community-fuelled efforts that germinated in the wake of AIDS had any equivalents in the Hep C world. If they might somehow be urged into existence. He dreamed aloud of what might result if HCV (Hepatitis C Virus) received the kind of attention enjoyed by HIV.
But, as we know, these viruses differ in a way which locks in a yawning disparity when it comes to potential advocacy.
And what way is that?
It’s the stigma. The stigma that surrounds injecting drug use. The stigma so embedded in our societal norms that it is, as they say, enshrined in law.
Dr Sunil Solomon is an Associate Professor of Medicine at the Johns Hopkins University School of Medicine. During the plenary session, he put on a compelling show. Beneath the rubric of ‘No One Left Behind,’ he concentrated on two mantras.
The first was ‘every epidemic is different.’
Across the vastness of India, where most of his data was sourced, HCV prevalence varies from 4% to 64%, and in different sectors entirely different genotypes hold sway. When areas differ so fundamentally, it's obvious that tailored approaches are necessary.
But that’s just India: the Hep C battlefront encompasses the world - and it’s not just the epidemiology which shifts. Cultures do too. And also governments. Consider Russia - home of Krokodil, and of a government so averse to harm reduction they even refuse to offer the basics (like ORT (Opioid Replacement Therapy: i.e. methadone) and NSPs (Needle & Syringe Programs) - then compare it to Australia where billions are spent on Hep C mitigation.
Sunil’s second mantra? Integration.
He holds, with cast-iron certainty, that the integration of Hep C testing and treatment with NSPs, ORT and other user-related services should be a ground rule that applies worldwide. His research was convincing. It demonstrated that if ORT is linked with Hep C treatment, it has the potential to produce extraordinary results.
To some extent, Australia has adopted this same combinatory strategy, but as Melanie Walker of AIVL shows later in this post, we still have some way to travel. We are yet to fully exploit (and in some cases even identify) all points of contact between drug users and medical services.
According to Sunil, ‘every epidemic is different.’ However, the situation which prevails in India is very different indeed - at least to what we're used to in Australia.
For a start, testing for the virus in India costs more than the actual course of treatment. In Australia, when last I looked, treatment was in the ballpark of $50,000. In India, I'm guessing, it would be one per cent of that.
And as for hi-tech dosimeters? (At least one was presented at the conference, featuring, I think I recall, a foolproof laser grid) In India a cheaper method of ensuring treatment compliance is possible: that would be paying someone to go and actually put the pill in the patient’s mouth.
There are also some unusual cultural factors in play. India is a land where receiving an injection from a doctor or nurse is deeply symbolic of healing. Sunil described a Hep C trial in which almost every participant who was randomised not to receive interferon (and therefore no injections) was deeply disappointed. They were sceptical that pills, ordinary everyday pills might ever be more efficacious than injections.
To quote Sunil: We have such a high burden of Hep C in the general population because of our love for injections. It’s true! We want an injection for everything! We have a headache, we want an injection. We have a stomach ache, we want an injection…
Even the flu-like fever caused by interferon is commonly seen as a positive thing, a sign that the injections are working.
Speaking of interferon (pegylated interferon, to be precise) Sunil proposed that we ought not completely expunge it from our Hep C arsenal, despite the terrible reputation of its side-effects. In certain situations, he said, it may still be an optimal choice - particularly in combination with Ribavirin and certain DAAs, where it can reduce treatment duration to only four weeks.
Ugh. Even typing the word ‘interferon’ makes me queasy.
He used the devastating floods around Chennai in 2015 as an example. Pegylated interferon (with one injection per week) has a much longer half-life than DAAs (with at least one pill a day). During the floods, where many patients were separated from their medical providers and/or drug supplies, those on the longer acting drug experienced less of an interruption to their treatment.
Sunil also made the point – an interesting one, I thought – that the miasma which hangs over the reputation of interferon may largely be due to the long-outmoded regimens of 24 to 48 weeks. If the drug had only ever been prescribed for four weeks, then the side-effects may have been more tolerable, and today it may not strike quite so much fear into the hearts of all those to who it has been prescribed.
Melanie Walker, the CEO of AIVL (the peak body for all Australia’s peer-based harm reduction outfits (including HRVic)) listed some areas of concern where the elimination effort is failing to penetrate - or experiencing less than spectacular success.
Dealing with the virus in prisons is prominent in this regard, indeed the conference dedicated an entire track to this challenge. Melanie mentioned the obvious: the lack of any NSP services in prisons throughout the nation. This is a thorny issue, particularly with prison unions, but will ultimately need to be addressed.
Hep C prevalence is very high in prisons – it’s the perfect place to get infected, or reinfected, but a good amount of thought and effort is being put into the treatment of prisoners. It’s just that the prison system is extremely clunky, systems are deeply embedded and difficult to work around, particularly in higher security prisons. A prisoner may have been successful in making an appointment with a Hep C treatment nurse; and on the day they may have gone through hours of processing needed to move from their unit to the clinic - when a sudden lockdown makes their effort fruitless, and another appointment must be made, for however long down the track. People are being treated in prisons, certainly, but the process is far from ideal.
A prisoner may also be released midway through treatment. Keeping track of the comings and goings of prisoners is an unenviable task, and though work is being done in this area, maintenance of treatment after release is not yet systematic, although the Victorian state-wide prison treatment model run by St. Vincent's and funded by Justice Health is a good start.
One frontier broached by Michelle was ‘chemsex’. This is a relatively recent term: it emerged from the HIV sector, but has been gaining relevance in Hep C, particularly with the proliferation of methamphetamine. Chemsex is defined as ‘sexual activity engaged in while under the influence of stimulant drugs such as methamphetamine or mephedrone, typically involving several participants.’ Obviously, behaviour like this can lead to disinhibition, and to risks being taken. Among those co-infected with HIV & HCV there is a chance that both diseases may be transmitted during unprotected anal sex. Safe needle-use practices may also be abandoned in such an environment.
Of course, smoking is the traditional method of using ice, but Melanie pointed out that the seizure of ice-pipes by police, the inability of head-shops to display them for sale and NSPs to distribute them may be causing meth users to shift from pipe to needle - creating a risk of BBV (Blood-Borne Virus) infection. It’s absurd, really, that obtaining syringes should be easier and basically more legit than obtaining ice pipes.
But this is not the only elementary harm reduction service that is hobbled by regulation. A licence is required in Victoria for the distribution of injecting equipment to anyone other than oneself. This has implications, for example, in rural areas unserviced by NSPs. Someone who travels to a larger town and brings home a box of clean fits to distribute among their friends is effectively committing a crime. Melanie stressed a need for legislation be quickly passed to iron out such anomalies, which seem to stand in the way of the state government’s stated Hep C elimination policy.
AIVL is also engaged in an investigation of users and aged care settings. ‘A greenfields site,’ as Melanie termed it, as it seems to be a subject which no one has properly addressed.
What are people who have injected drugs for the bulk of their lives to expect if fate demands that that they retire to an old folks’ home?
Nothing good, it seems. There is some evidence that users are actively avoiding engagement with aged care services precisely because they have no idea what they are stepping into. Are OST services provided? NSPs? Are there staff members with AOD experience? Will they be able to continue using their drugs of choice?
To me, old age should be a time in life where such concerns should be put aside, not a time of anxiety-provoking change. But ugly images tend to come to mind if one pictures, say, the reaction of a commercial nursing home manager upon being informed that heroin is being injected on his premises.
Horror stories regarding abuse of the elderly emerge regularly in the press - be it bedsores or kerosene baths. I shudder to think of how users might be treated, given the extra layer of stigma and discrimination to which they are reliably subject.
Hep C infection, detection and treatment is relevant here too. Is there testing? Could there be testing? Perhaps on arrival? Is there an opportunity for treatment?
The generation bearing the heaviest burden of Hep C in Australia will soon be facing their golden years. A progression into aged care or assisted living may be an opportunity to improve, or even save, the lives of those who, to that point, have slipped through the cracks. Who, perhaps, no longer have contact with services likely to offer HCV testing, or who may have avoided testing for reasons around stigma and discrimination.
At the very least, one would expect relevant services to be offered, for staff to be familiar with the disease, to know how to address it, and to operate under sensible, informed policies. Perhaps this is already happening. Who knows? That's why it's such a good idea that AIVL had begun to probe the issue.
One talk which caught my interest (but for which I lost my notes) described the concept of trawling through Hep C notifications to check if the patient concerned had sought treatment, and, if not, to deliver a friendly suggestion. There was also discussion of how far back one could reliably go with this technique, given how personal details change over the years.
To me such thinking is useful - if elimination is the goal. I understand that in Australia a relatively high percentage of Hep C cases have, at some stage, been identified. Why not proactively (and sensitively, of course) make use of that data?
Finally, I’d like to echo the excitement around the rapid evolution of testing technologies. Simple dried blood spot essays for active virus should soon be a reality and processing time will continue to decrease. This opens the door for self-testing. Imagine being able to buy a Hep C test kit at a pharmacy -just like a pregnancy test or a bowel cancer screening kit. Just imagine that.
So that's it for the conference. I hope I've communicated the essence of it in these three posts, and in case you missed the first two, here they are
The Golden Phaeton
P.S. Beware the next Hepalogue post. I’ve got an absolute corker of an interview.