New hep C drugs strut their stuff
The nature and success rate of hepatitis C (HCV) treatment should be transformed in 2-3 years’ time, if early results from trials of a number of new drugs are anything to go by.
At the recent European AIDS Conference, Spain’s Dr Vincent Sorriano said that there were some 16 compounds currently under investigation as possible HCV treatments. They work in a similar way to HIV drugs, interfering with the way viral enzymes called protease and polymerase make new viruses. However in HCV viral elimination is possible, although interferon would probably always have to be included in anti-HCV combination therapy for a complete cure.
The following week at the American Association for the Study of Liver Disease (AASLD) Conference, results from trials of three new drugs were presented.
The furthest along in development is nitazoxanide (Alinia®). This drug was originally developed as a treatment for the AIDS-related bug cryptosporidium, but it was then found to have anti-HCV properties.
The study presented at AASLD was conducted in Egypt, which has high levels of infection with genotype 4 of HCV, a subtype of the virus that is particularly hard to treat and is increasingly spreading to southern Europe.
The addition of nitazoxanide to standard pegylated interferon/ribavirin (pegIFN/RBV) therapy increased the proportion of patients cured of genotype 4 from 48% to 79%. When used with pegIFN alone and no RBV the cure rate was 68%.
Nitazoxanide manufacturers Romark are currently conducting a large trial of the drug in the USA for patients who’ve failed previously on standard pegIFN/RBV therapy and who have HCV genotype 1, the other hard-to-treat kind. They will start a trial in patients new to therapy in 2008.
The two other drugs presented have so far only been used in short 14- or 28-day trials by themselves to check for their safety and see how they work against HCV.
They so far are only designated by the numbers R1626 and R7128 and are being developed by Roche, who make the Pegasys brand of pegIFN. Both are nucleoside polymerase inhibitors.
The first drug given twice-daily for 28 days produced an undetectable HCV viral load in 81% of patients given it, with an average 160,000-fold viral load reduction. The second, given in four different doses for 14 days, produced a 500-fold viral load drop at the largest dose, with one person already reaching undetectability by this time.
The two drugs are being advanced into larger treatment studies in combination with pegIFN/RBV.
Hepatitis C treatment improves mental health
Successful treatment of hepatitis C (HCV) in patients both with and without HIV results in measurable improvements in mental agility, mental health and quality of life post-treatment, an Australian study has found.
Although deteriorations in mood and mental ability happened while patients were actually on treatment, these being well-known side-effects of interferon, these were back to normal six months later.
By this time cognitive function (mental ability) had bounced back to pre-treatment levels for the HCV patients and was considerably better than pre-treatment levels for the HCV/HIV patients.
Mental health in terms of depression, anxiety and stress was considerably better post-treatment than pre-treatment for the HCV mono-infected patients and back to pre-treatment levels, though not improved, for the HIV patients.
Given that HCV, HCV treatment and HIV all affect the brain, few studies have been done of the mental effects of HCV treatment. This was too small a study to tell us a lot, and larger studies are needed to see to what degree HCV treatment really does improve patients’ mental functioning.
• HIV Medicine 8(8), p 520-528.
Faster liver damage in
HIV/HCV patients
In the absence of effective HCV treatment, a quarter of patients with hepatitis C who also have HIV experience significantly worsening liver damage within three years, a US study has found, regardless of their initial liver health or whether they take HIV drugs. Liver damage is graded on a ‘fibrosis scale’ of F0 to F5 and 24% of the patients had advanced at least two points within this time, with a calculated rate of 0.89 points a year. One in five of the patients had HCV treatment during this time but only one in 50 were cured of HCV – and these few experienced no progression.
Treatment reduces deaths – if it works
A study of over 450 French patients with HIV and HCV finds that successful HCV treatment considerably reduces death rates. Over half of patients at the Pitié-Salpetrière clinic in Paris had HCV treatment, but it only worked in 40% of them, or one in five of the whole group. Over a ten-year period one in every 22 patients died, and one in 12 patients who took HCV treatment – because treatment was reserved for those with worse liver damage. But in the group of patients where HCV treatment was successful, fewer than one in 80 died. Dr Stéphanie Dominguez commented that HCV treatment should be started sooner.
High HCV, but not HIV rates in UK
drug users
Forty per cent of the estimated 140,000 people who inject drugs in the UK has hepatitis C, and this goes up to 60% in London and the north-west, a survey by the Health Protection Agency has found. If found that although heroin was still the most likely drug to be injected, 33% of users had injected crack, and crack users were more likely to have HCV. HIV rates in injecting drug users remain low, however, with only 1.3% nationwide having HIV, though that rises to 4% in London. Encouragingly, three-quarters of drug users in touch with healthcare providers have taken a hepatitis C test, up from 50% in 2000.
Few patients cure themselves of HCV
A survey of patients with acute (recently-caught) hepatitis C has found that fewer than previously thought rid themselves of the virus. When people catch hepatitis C, a minority – usually estimated as 15% - fight off the infection, a phenomenon called spontaneous viral clearance (SVC). However a survey of 150 patients at four European hospitals, most of them gay men who got HCV through sex, found that only 8% achieved SVC without HCV treatment – though a few who took treatment might have done so too. Dr Alex Azwa said the most striking finding was that only a quarter of patients who appeared to have got rid of their HCV three months after infection had actually done so – in the rest it reappeared, anything up to a year later.
