How Simple Can It Get? – New Study Yields Promising Results on Rapid Hep C Testing.
As recently as a few years ago, Hep C treatment required a serious commitment from the client: frequent hospital visits and blood tests; bi-weekly self-injection with seriously nasty side-effects; sometimes a liver biopsy, an ECG and even a session with a psychiatrist. All this with a duration of treatment that could extend beyond six months - and only a one in two chance of a cure.
But now the cure is almost guaranteed. What’s more, it can take as few as eight weeks to achieve, has next to no side-effects and only involves dropping a pill or two each day.
The blood tests remain, but there are fewer of them. Given the safety of the medications, it is no longer necessary to so closely monitor a patient’s status for conditions like anaemia or neutropenia. With the advent of Epclusa and other pan-genotypic DAAs, it is not strictly necessary to test for the strain of the virus.
It is even possible to access treatment from a local GP (with no involvement from a specialist) and the medications may be acquired from most pharmacies.
Not too demanding on the face of it, yet some researchers suspect that a further simplification of the process could bring more people into treatment.
According to figures from the Kirby Institute there has been a slowdown in treatment uptake in Australia since the heady days directly after the PBS listing of the first DAAs. At that time more than 4,000 people were accessing treatment each month. That figure has dropped to as low as 1,500.
Thus far, a reasonable dent has been made the country’s pool of infection (in the vicinity of 20%) but this included a population of pre-engaged clients – often referred to as ‘low hanging fruit’ – who were champing at the bit and who fronted up for treatment within the first months of it becoming available.
Obviously, if the elimination effort is to succeed, access must be gained to the large numbers who have yet to be treated. It is also vital that successful treatment outcomes outpace the instances of new infection (of which there continue to be a significant number).
A large percentage of those with the disease are unlikely to spread it - either because they no longer inject or they have never injected, having acquired the virus via some other route. This population should be encouraged into treatment, of course, but in epidemiological terms it is clear that attention should be focused where infection continues to spread: i.e. among the active injecting community.
This is also a community where streamlining of the treatment process may be particularly useful. Current injectors are more likely to be marginalised, with financial, legal or accommodation issues. They may be embroiled in forms of chaos which cause Hep C treatment to pale as a priority - particularly as it is a slow-acting, chronic disease that may have few noticeable symptoms.
One can easily imagine how a treatment burden involving numerous appointments at various sites, long hours in waiting rooms, nasty instances of stigma, and the potential for frustrating, fruitless blood-taking sessions may push Hep C treatment down on the average injecting user’s to do list.
With this in mind, the Eliminate C Partnership and the Burnet Institute (led by Prof. Margaret Hellard) designed and implemented the Rapid-EC Pilot Study, sought to examine the results of making treatment as simple and immediate as possible for the injecting community, using new technologies and clinical methodologies. This strategy - of reducing the inconvenience of testing to the barest bones – is generally referred to as RPOC (Rapid Point of Care).
The researchers partnered with three community health clinics (Inner Space, Healthworks and North Richmond Community Health). All three gear their services towards active injectors/pharmacotherapy customers and operate NSPs (Needle and Syringe Programs) on their premises. It was from the clientele of these NSPs that subjects from the study were recruited.
So, exactly how rapid and simple did they manage to make it?
At the initial appointment, a mouth swab was taken from the subject. 20 minutes later, they learnt if they had antibodies to the Hep C virus. If the result was positive (meaning they had been in contact with the virus at some point in their life) the next step was to take blood, which was tested onsite using PCR technology. 2 hours later they could find out if they had an active infection requiring treatment.
For those carrying the virus, a follow-up appointment was then arranged, to review their full blood results, including liver & kidney function, the presence of cirrhosis and/or coinfections with HIV/Hep B. This appointment could occur as soon as the tests were completed, and was necessary because some more complex cases may require special treatment. For example, it is recommended that those with cirrhosis take a longer course of medication. (Of the participants in the Rapid-EC study very few were found to be cirrhotic.)
From the second appointment on, the researchers released their subjects into the hands of the clinic, where they accessed treatment in the usual way: a script for Epclusa, a visit to the pharmacy and a pill each day for twelve weeks. (If compliance presented any sort of problem, some of those on pharmacotherapy were able to have their medication dispensed along with their methadone/buprenorphine.)
Success of treatment will be ascertained by a blood test twelve weeks after the end of treatment (commonly described as ‘SVR12’).
Now, it might be a stretch to call this process rapid – but in comparison to the previous system it is a massive abridgment. A significant obligation, sure, but much less of one. Additionally, as part of the study’s underlying philosophy, workers attempted to be as flexible and as understanding as possible. Participants were not punished or excluded if they failed to abide by their commitments. Instead, an effort was made to identify any hurdles a client may be facing, and then develop strategies to address them.
The choice of clinics was important in this regard. All three, but notably (Footscray’s) Healthworks, provide an easy-going, nondiscriminatory, non-clinical atmosphere. Whenever possible, the study also encouraged the involvement of peer workers, some of who even completed phlebotomy courses so that they could participate in actual hands-on treatment. As much as was possible, study participants interacted with perceived equals in a familiar, relaxed environment where there was little threat of stigma.
Ultimately though, when it comes to achieving something truly rapid, the major choke-point seems to be the technology itself. Though the mouth swab is nice and quick (OraQuick HCV Rapid Antibody Test ) the subsequent RNA assay (Cepheid Xpert) takes a significant length of time. What’s more, it involves phlebotomy, a procedure that comes with its own issues, particularly with a client population more likely to have compromised veins.
Less than 10 participants waited out the two hours on site to receive their RNA result, with the vast majority opting to receive their result via phone call or text message. Well, wouldn’t you? The more rapid the better, it seems, when it comes to attracting and retaining members of challenging client populations, and this was evidenced by actual testimony from the subjects.
Regarding the technology, there is definitely light on the horizon. Though the tests used were new (special leave was required from the TGA as they have yet to be approved) the pace of development in the field of diagnostic tools is extraordinary and improvements are already in the works. Inevitably, the machines will become speedier, less bulky and prices will drop. (Consider the cost of mapping the human genome: fifteen years ago, it cost Craig Venter USD100,000, today you can have it done for USD250 or less.)
Happily, some of the new development paths involve fingerprick tests and dried blood spot analysis, techniques which may soon remove the need for venepuncture. (It may be worth mentioning, though, that any method not using whole blood - including the mouth swab used by the Rapid-EC study - carries a slightly higher risk of an inaccurate result. Yet as the technology matures, it is likely that this issue will evaporate.)
More than anything, the Rapid-EC study provided a proof of concept. Results definitively showed that clients who were previously shy of what was seen as a complicated process might be lured into treatment by a pared down system and a caring, stigma-free, minimally threatening environment.
85% of subjects considered the process designed by the study an improvement, but few saw it as ‘rapid’ and would have preferred a reduced timeline. From my own perspective, I wonder if the process might be improved by making it possible to obtain the drugs in situ and for free. $20 or so for a three months course may not seem like much, but for many members of the target community it is. Given a particular day and a particular set of circumstances, purchasing medication may not figure on their list of priorities.
The research project also came with a few overheads which would not be present in everyday practice. Subjects, for example, were asked to complete ‘demographic, behavioural and acceptability surveys’ – something that would obviously not be required if RPOC methodologies penetrate mainstream practice.
Researchers are first to admit that lessons remain to be learned. “Particularly with regards recruitment,” says Burnet’s Dr. Alisa Pendrana. “It took us a few months to bed down that process. We had slow numbers initially, compared to expectations, and it had us worried. But with any new clinical system there was a settling-in process: training, dynamics, changing clinic mechanics …”
Initially, given the novelty of the study, the researchers were uncertain how many participants they would recruit, but made a rough prediction of 200. In the real world this manifested as a very satisfactory 174. Of these, 150 (86%) returned a positive result on the mouth swab. 140 (93%) of these (minus about 10 from who blood could not be obtained) received the 2-hour RNA test and 76 (54%) were found to have the virus.
The median age of participants was 41 years. This is an encouraging number: a little higher than that of the average NSP user, but considerably lower than the average age of those already treated across the country. It suggests that the study may have begun to penetrate an under-treated age demographic: those who are younger, with less advanced disease, and who may not yet view treatment as urgent.
As strong proof the study was accessing patients with a significant likelihood of spreading the disease, 88% of participants had injected drugs and 53% had shared injecting equipment within the previous six months.
Of those who had Hep C diagnosed with the rapid test, 63% came back for the second visit and were linked to follow up care.
On the face of it, one might predict that the results of such a study would be successful. A no-brainer really. But in science and public health, you do have to actually prove stuff – and the Rapid-EC study appears to have done just that. Thoroughly. Though the number crunching process continues and new interpretations continue to emerge from the data, preliminary results strongly support the study’s hypotheses.
Streamlining works, then, for clients, health workers and for public health officials, but what was the reaction of the cooperating clinics? I spoke to Danny Jeffcote, the program manager at Healthworks, who was effusive on the subject.
“We’re disappointed it’s over, and that we no longer have access to the technology.
“Though it wasn’t as rapid perhaps as we would have liked, being able to get the results and do everything onsite really helped us as a practice, as a service delivery organisation.
"This was an opportunity to involve our NSP staff a little more. We had the chance to take some from behind the NSP desk – which is where they usually start out – and train them to deliver clinical services to clients. For us that’s huge.
"We’re keen for there to be a second round of the study - this time, hopefully, with blood spot testing for PCR….”
It so happens that another related study is planned by the Burnet Institute/EC Partnership, though it is not based on improved technologies. Rather, the intention is to follow up on the idea of peer-delivered services.
“We really want to demonstrate the value and the impact of having peers engaged in people’s Hep C treatment,” says Dr. Pedrana. “The funding has been approved and over the coming months we’ll be designing the study together with other stakeholders” (like HRVic).
“This is will be less clinical than the last study. It’s likely to be more about engaging the infected population, educating them, creating an increased awareness and uptake of treatment.
“It may also involve a kind of assisted referral, where peers can actually refer members of the infected population into specific services.”
The Golden Phaeton