Who should receive treatment?

Due to the side-effects and relatively low response rates of current HCV treatments, treatment is not indicated for everyone with chronic HCV infection. Therapy is indicated for people who are experiencing liver disease progression. Since HIV seems to accelerate HCV-related liver damage, some experts think co-infected people should be treated earlier in the course of the disease.

There is large variation in responses to HCV treatment. People less likely to respond well include:

• Symptomatic people with moderate or severe fibrosis or cirrhosis of the liver.
• People with HCV viral loads greater than 2,000,000 copies/ml.
• HIV/HCV co-infected people with CD4 cell counts below 500 cells/mm³.
• People with HCV genotype 1, especially subtype 1b.
• People of African descent.
• Men.
• Older individuals (above age 40).

People with fewer symptoms, lower HCV viral loads and genotypes other than 1 tend to respond better to treatment, but they also typically have a lower risk of liver disease progression, lowering the urgency of treatment. This forms a paradox: those who are most likely to benefit from HCV treatment are those who need it least.

As HCV therapies improve, the balance between treatment benefits and risks are likely to continue to change. Not all experts agree about who should receive treatment and the best time to start.

Traditionally, most doctors preferred to treat only individuals whose liver functions are consistently abnormal. However, recent research indicates that some people with persistently normal ALT levels may still experience liver disease progression and could benefit from therapy.^{1 2}

Interferon-based treatment does not work well and can be dangerous in people with decompensated cirrhosis. Clinical trials are underway to determine the best way to treat individuals with advanced liver disease.

Because it is usually asymptomatic, HCV infection is rarely detected during the acute phase, in the first six months. However, among co-infected people on HAART who receive regular liver function tests, the detection rate is higher. HCV treatment during the acute phase of infection is highly effective, approaching 100% in some studies of HIV-negative people.³

Among HIV/HCV co-infected individuals, the response rate during acute infection is lower but still good, around 60 to 75% in different studies.^4,5,6,7,8,9  However, treating HCV at such an early stage means that many people who would have spontaneously cleared the virus or never developed liver fibrosis will receive unnecessary treatment. United Kingdom and United States guidelines recommend that early treatment should be considered, but that it is prudent to wait two or three months to see if spontaneous HCV clearance occurs.¹⁰ 

According to data from a leading UK sexual health clinic, only 25% of HIV-positive patients with acute HCV infection are actually accepting HCV treatment.

As for hepatitis C alone, the standard anti-HCV regimen for HIV/HCV co-infected people is peginterferon plus ribavirin. In February 2005, the European Commission and the United States Food and Drug Administration (FDA) approved peginterferon alfa 2a (Pegasys) for use with or without ribavirin for co-infected patients with chronic hepatitis C.

Because co-infection with HIV accelerates HCV-related liver disease progression, some experts argue that all co-infected people should receive anti-HCV therapy.¹¹  Researchers who found that HAART has no impact on the development of fibrosis in co-infected people have argued that treatment for hepatitis C should be started as soon as possible.¹²

United Kingdom guidelines recommend that HCV treatment should be considered for all HIV-positive individuals, particularly if they have developed moderate or worse liver disease. Treatment ideally should be initiated whilst a patients CD4 cell count is above 200 cells/mm³, as treatment at lower CD4 cell counts has been associated with a poorer response. Treatment should also be considered in the case of mild disease, particularly if the patient wishes to commence treatment and there are high hopes of success. In cases of advanced cirrhosis or liver cancer, co-infected patients can be good candidates for liver transplant if their HIV prognosis is good. Individuals with hepatitis C co-infection may wish to consider early antiretroviral treatment, at a CD4 count between 500 and 350 cells/mm³, 2008 BHIVA guidelines state.

The usual recommendation is that co-infected individuals should continue HCV therapy for the same duration as people with HCV alone (48 weeks for genotype 1; 24 weeks for genotypes 2 or 3). However, some research suggests that co-infected people clear HCV more slowly after starting treatment, and some experts recommend lengthening treatment duration to 72 weeks for genotype 1 and 48 weeks for genotypes 2 or 3.¹³ The benefits of 48 week treatment for genotypes 2 or 3 have been confirmed in a small randomised controlled trial of HIV-co-infected patients. In this study, patients receiving peginterferon alfa and ribavirin for 48 weeks were over five times more likely to achieve an SVR than those who stopped therapy after 28 weeks.¹⁴

Guidelines on the management of HIV/HCV co-infection published by the British HIV Association (BHIVA) in 2005 make the following recommendations:¹⁵

• Screen all HIV-positive patients for HCV at HIV diagnosis and subsequently according to risk.
• Perform a PCR test in patients with unexplained liver disease.
• HIV/HCV co-infected individuals should be vaccinated against hepatitis A and B.
• Monitor patients thoroughly, including liver biopsy to assess disease severity.
• HIV/HCV co-infected patients should abstain from alcohol.
• Consider treatment with peginterferon plus ribavirin, or enter into a clinical trial. Treatment is most appropriate in patients with moderate disease.
• Treat patients who have a CD4 cell count above 200 cells/mm³ before commencing HAART, if possible, to reduce risk of liver toxicity.
• In patients who are already on HAART, delay HCV therapy until CD4 cell count is above 200 cells/mm³.
• AZT (zidovudine, Retrovir) and ddI (didanosine, Videx / VidexEC) ideally should be avoided in patients receiving ribavirin.
• Monitor liver function carefully if HAART is initiated and observe serum lactate for nucleoside analogue toxicity, especially in those on ribavirin.
• All HIV-positive patients with HCV who do not have evidence of liver damage should be screened annually.
• Patients who eradicate HCV should have PCR performed annually to detect relapse or re-infection.
• Patients diagnosed with acute hepatitis C may be treated with pegylated interferon plus ribavirin.

An international consensus statement on the treatment of co-infection calls for:

• Consideration of therapy in patients with normal ALTs.
• Assessment of fibrosis, with non-invasive techniques considered generally able to replace biopsy.
• Use of early HCV virologic response to predict SVR outcome.
• Standard doses of peginterferon plus weight-based dosing of ribavirin for HCV treatment.
• 48-week HCV treatment with consideration of adjusted duration of therapy.
• 24-week treatment of acute HCV infection.
• Avoidance of AZT and complete avoidance of ddI with ribavirin.
• Individualised management of drug-related hepatotoxicity.¹⁶

Ideally, assessment and treatment for HIV and HCV should be carried out in a specialised unit experienced in treatment of both conditions and there should be liaison with the local hepatology team.