Favourable response seen with PEG-IFN/ribavirin during acute hepatitis C co-infection

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Treating hepatitis C (HCV) during the first six months of infection can lead to a high rate of clearance in those co-infected with HIV -- as long as the treatment is tolerated -- according to a presentation by researchers from London’s Royal Free Hospital at the 10th Anniversary Conference of the British HIV Association (BHIVA) in Cardiff last week.

Since October 2002, 38 gay men attending the Royal Free’s HIV clinic, who were already chronically infected with HIV, have been identified as being newly infected with HCV. Only six of the men (15%) were diagnosed due to symptoms related to acute HCV infection (e.g. jaundice, diarrhoea and nausea). A further twelve men (30%) had their HCV infection picked up during routine sexually transmitted infection (STI) screening. The majority (55%) were diagnosed after their routine liver function tests indicated that further investigation was warranted. All HCV infections were confirmed by positive HCV RNA (viral load) testing.

The average age of the co-infected men was 30.5 years, median CD4 count was 514 cells/mm 3(range 207-943) and 18 (48%) were on HAART at the time of diagnosis. Twenty of the men (52%) had also been diagnosed with another STI in the prior six months, adding weight to the assumption that the mode of transmission was sexual, since no other traditional risk factors have been found.

Glossary

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

traditional risk factors

Risk factors for a disease which are well established from studies in the general population. For example, traditional risk factors for heart disease include older age, smoking, high blood pressure, cholesterol and diabetes. ‘Traditional’ risk factors may be contrasted with novel or HIV-related risk factors.

withdrawal

In the context of drugs or alcohol, withdrawal is when a person cuts out, or cuts back, on using the substance, also known as detoxification or detox. In a context of sexual risk reduction, it refers to the insertive partner in penetrative sex withdrawing before ejaculation. It is not a particularly effective way to lower the risk of HIV transmission or pregnancy.

response rate

The proportion of people asked to complete a survey who do so; or the proportion of people whose health improves following treatment.

The majority (58%) were infected with genotype 1, which is more difficult to clear once the infection becomes established compared with genotypes 2 and 3; however there are few data on the success rate of treating acute genotype 1 HCV co-infection.

All of the men were offered treatment with pegylated interferon and ribavirin – the ‘gold standard’ of chronic HCV treatment -- after 12 weeks of persistently testing HCV viral load positive. Seventeen men agreed to start treatment, thirteen of whom were infected with genotype 1, three with genotype 3, and one with genotype 4. Their median HCV viral load was 5.86 log10 at baseline.

Since all the men were diagnosed at different times, the length of follow-up reported at Cardiff ranged from twelve to 48 weeks. Data to week 12 were reported on fifteen of the men. Eleven of the fifteen on treatment (73%) achieved an early virological response, which was defined as either an HCV viral load below 50 copies (‘undetectable’) or a two log viral load decrease.

Twenty-four week data were reported for nine men, of whom six (66%) achieved an undetectable HCV viral load.

Forty-eight week data were available for seven men, of whom five (71%) had an undetectable HCV viral load.

Of the remaining 21 men who did not take anti-HCV therapy, nine were reported as having spontaneously cleared their HCV infection. This is a much higher number than expected -- around 10% of all infections spontaneously clear in people not co-infected with HIV -- although it is possible that re-appearance of HCV viral load may occur at some point in the future.

The Royal Free researchers reported a 30% withdrawal rate, reflecting the difficulty of tolerating interferon therapy due to its major side-effect: severe depression.

The Royal Free results correspond closely to the real life results reported at last year’s BHIVA conference by Mark Nelson and colleagues from the Chelsea & Westminster Hospital, and reported in the June 2003 issue of AIDS Treatment Update (Issue 126). Although the on-treatment success rate at the Royal Free appears to be around 70% -- much higher than even the recently-reported APRICOT results of 40% in co-infected people with chronic HCV infection -- less than half of the men offered treatment took it: and of those that took it, 30% were unable to tolerate it long-term.

However, considering that the majority of those who achieved treatment success were infected with genotype 1 -- of whom only 29% achieved success in APRICOT -- the researchers suggest that treatment of HCV co-infected individuals with pegylated interferon and ribavirin during the acute stage of infection has a favourable response rate. At the moment, the BHIVA guidelines on HIV/HCV co-infection recommend only “consideration” of using pegylated interferon with or without ribavirin, with standard interferon suggested as first choice.

Further information on this website

Treatment for HIV/HCV coinfection: three major studies report at CROI - news story, February 2004

Barebacking the sole common risk factor in London's sexually transmitted hepatitis C epidemic - news story, October 2003

AIDS Treatment Update, HIV & HCV co-infection - Issue 126, June 2003 (pdf file)

References

Bhagani S et al. Acute hepatitis C virus (HCV) in a cohort of HIV-positive men: outcomes and response to pegylated interferon-alpha2b and ribavirin. 10th Anniverary BHIVA Conference, Cardiff, abstract 020, 2004.