Despite being tough-going and time-consuming, treatment for hepatitis C in people living with HIV is gradually improving
Words Robert Fieldhouse
Image Raffaele Teo
Experts
reckon we have only identified around one per cent of the people who have
hepatitis C (HCV) in the UK. A recent report from the Hepatitis C Trust painted
a dismal picture of the way the UK has fallen behind its European neighbours
when it comes to treating this virus.
Treatments for HCV, a liver disease, offer the chance of a cure (for some)
but can be extremely tough to stick with, as the side effects can be particularly
nasty. In the largest study of treatment for hepatitis C in people coinfected
with HIV, around one in four who took pegylated interferon and ribavirin (the
current gold standard treatment) stopped their treatment during the trial
because it was so hard- going, and because being HIV positive too means you
are less likely to clear the virus. All in all, rather a miserable prospect,
you could argue.
Sue Russell, clinical nurse specialist in hepatitis at North Manchester General
Hospital, takes a more optimistic stance. Speaking at a recent hep C/HIV information
event co-ordinated by the UKC, she said: “You might have to put your
life on hold for 48 weeks, [the time people with HIV need to spend on HCV
treatment] but for some it’s worth it as you are putting time in the
bank for the future.” There are six major strains (genotypes) of hepatitis
C. In the UK, most people are infected with strain 1, 2 or 3. The best treatment
response rates are among people infected with genotype 2 or 3.
Not all bad news
Dr Janice Main of St Mary’s Hospital, London, has provided care to people
coinfected with hepatitis and HIV since the 1980s. She told the audience at
the UKC event: “The liver is good at regenerating itself; you can survive
with around 10 per cent of it functioning. “Just a few short years ago
only six per cent of people treated with the old-style thrice weekly injections
of interferon could be expected to clear the virus. Currently over half (54
per cent) of people who take pegylated interferon and ribavirin get a sustained
virological response (SVR), which is commonly regarded as a cure.” SVR
means the absence of hepatitis C virus six months after 48 weeks of therapy.
What does the liver do?
The liver is a big recycling plant, dealing with waste products. When red
cells get to the end of their life they are fed through the liver. The liver
stores glycogen, a fuel which drives our brains, and it stores fat. It is
one of the major immune organs of the body; bugs in the blood can be mopped
up there. It also stores fat-soluble vitamins.
If you are co-infected...
If you are HIV positive you are more likely to have higher levels of hepatitis
C in your blood. Co-infected women are more likely to have higher levels of
hepatitis C in their cervicovaginal fluid and co-infected men are more likely
to have higher levels in their semen, which could make you more infectious
to sexual partners. Coinfected women are more likely to transmit HIV or HCV
to their baby.
What if I think I may have been recently infected with hepatitis C?
Ask your HIV clinic to test for the virus itself. There is little point doing
an antibody test if you have acquired the virus very recently, as it takes
time for antibodies to be produced. It is worth remembering that it may take
decades for damage to the liver to develop; a decent CD4 count can put the
brakes on hepatitis progression.
If you have a mild disease and you are genotype 1, it may be worth waiting
a while for better treatments to become available. Some doctors think that
people who are caught at this very early stage of infection are most likely
to clear the virus if they begin therapy as soon as possible. Dr Mark Nelson
from the Chelsea and Westminster Hospital, London, treated 27 co-infected
people soon after they were exposed to hepatitis C and almost two thirds (59
per cent) were cured. However, this is lower than the cure rate (98 per cent)
seen when people who only have hepatitis C are treated soon after exposure.
What is the best therapy?
The largest study of pegylated interferon and ribavirin was Roche’s
APRICOT study which enrolled over 800 people co-infected with HIV and hepatitis
C across the world.
In genotype 1, the hardest to treat genotype, 38 per cent cleared the virus
and 29 per cent got a sustained virological response. In simple terms, this
means one in three were cured of hepatitis C infection.
If people were infected with the easier-to-treat genotypes 2 or 3 infection,
62 per cent developed a sustained virological response or cure. A separate
Spanish study showed that a person’s response to hepatitis C treatment
12 weeks after starting can be used to help decide whether to continue treatment.
If the amount of hepatitis virus in your blood does not decline significantly
by week 12 it is unlikely to do so over 48 weeks of therapy and you and your
doctor can decide to stop and wait for future therapies. It is important you
optimise your HIV care. Get your CD4 count as high as possible before you
start hepatitis C treatment, and avoid the so-called ‘d’ drugs
(nucleoside analogues such as ddI, ddC or d4t). It may be sensible to avoid
nevirapine too.
What if I have advanced liver disease?
If you have liver cirrhosis you have a one to five per cent chance of developing
liver cancer each year. Two trials looked at treatment for people with cirrhosis.
Low-dose interferon maintenance therapy has been explored as one option to
dampen down damage to the liver.
A
Mancunian response to coinfection
Manchester, where Sue Russell works, has a population of 2.4 million. Over
1,500 people are receiving HIV-related care in the North West, 250 of them
are co-infected with HCV and 30 have hepatitis B, too.
Everyone known to be HIV positive gets an annual or twice yearly HCV test
should their sexual activity warrant it. Between April 2004 and 2005 the service
received 520 referrals from local PCTs, community drug teams and local prisons.
Ninety-three of these people were treated. Between April 2005 and 2006 the
service expects to treat 120. There is a three month wait for treatment. During
this period Sue prepares people for what may await them, “like HIV,
hepatitis C is a life-changing diagnosis. Having a realistic picture of the
side effects can help you to get through the treatment. People can lose up
to two stone in weight, lose their hair in patches, and aren’t allowed
to use chemicals on their hair.
“Around 50 per cent of people who begin hepatitis C treatment in our
clinic experience depression which requires antidepressants. Because of lack
of appetite we advise people to have small, frequent, high-energy meals. Around
15 per cent of people get mild side effects and another 15 per cent get severe
ones; the rest fall somewhere in between.” Patients can be admitted
to the ward to begin hepatitis treatment. After an initial one and a half
hour appointment people are able to inject themselves once-a-week at home.
Sue can refer co-infected people to receive complementary therapies at Body
Positive North West, and she also has access to a clinical psychologist.
What
does the future hold?
Currently, only a liver biopsy can define mild, moderate or severe liver disease.
Nowadays these tend to be guided by ultrasound scanning. In the future more
sophisticated blood tests may be able to diagnose liver damage; good news
for anyone who is terrified at the idea of having a tiny part of their liver
cut out.
It is hoped that one or more of several experimental therapies now in development
for HCV infection will prove both more effective and less toxic than current
treatments. There are currently more than 30 drugs being studied for the treatment
of hepatitis C.
Final thought
Many people don’t always realise that it is possible to be reinfected
with the same or a different strain of hepatitis C even if they have successfully
undergone a course of treatment. Condoms for sex and not sharing notes or
straws to snort or needles to inject drugs can reduce the risk.
Drugs in the pipeline
Valopicitabine
Valopicitabine, an RNA polymerase inhibitor from Idenix Pharmaceuticals, is
the most progressed in clinical trials. In a 15-day study of valopicitabine
alone, the drug reduced the hepatitis C virus in the blood by an average 1.2
log (94 per cent) in people with HCV alone, most of whom had previously experienced
treatment failure with interferon and ribavirin. Combining valopicitabine
with pegylated interferon appears more potent than valopicitabine treatment
alone. The treatment was well tolerated, with no serious side effects reported,
At week 12, patients receiving valopicitabine plus pegylated interferon had
an average reduction in HCV virus of -3.01 log compared to -0.87 log in the
valopicitabine monotherapy arm.
SCH 503034 and VX 950
Two other experimental hepatitis C drugs have recently completed early stage
clinical trials: SCH 503034, made by Schering Plough, and VX-950, made by
Vertex Pharmaceuticals. Both compounds are inhibitors of the HCV protease
enzyme, which the virus uses to replicate itself.
Results from a clinical study of SCH 503034 were due to be presented as this
edition of PN went to press: see next month’s Treatment News for details.
Schering Plough are due to initiate a dose-finding study of SCH 503034 that
will provide the dosing information required to conduct a complete clinical
development programme. VX-950 has demonstrated good tolerability and a decline
of four log in HCV virus after 14 days of treatment in people with HCV genotype
1 infection. A study of 34 patients with chronic hepatitis C genotype 1 showed
that every patient receiving VX-950 achieved greater than a two log reduction
in HCV virus within the first three days of treatment. This, alongside a slow
return to original levels of HCV replication when therapy was stopped, means
that the drug could be explored for use alone, without interferon or ribavirin,
though studies combining the drug with each of these compounds are currently
underway.
Viramidine
Viramidine, produced by Valeant Pharmaceuticals, is a product of ribavirin.
It is converted to ribavirin mainly in the liver, and as a consequence produces
less anaemia, often the most limiting side effect of ribavirin. It has been
shown to be as potent as ribavirin, though the numbers included in the studies
so far have been small.
Although the drug, like ribavirin, has no direct antiviral effects on the
hepatitis C virus, it could act to strengthen the anti-HCV activity of interferon.
Preliminary results of Phase III studies of viramidine should be available
by the end of December 2005.
