Higher levels of adherence to hepatitis C therapy improve treatment outcomes in people with hepatitis C and HIV

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Higher levels of adherence to pegylated interferon and ribavirin are associated with better hepatitis C treatment responses in people with HIV and hepatitis C co-infection, US investigators report in AIDS and Behavior.

Adherence to both anti-hepatitis C drugs fell during the 48 weeks of therapy and methadone use was a risk factor for poorer levels of adherence.

“These results show that adherence to anti-HCV [hepatitis C virus] medication should be a focus of clinical care teams prior to and throughout HCV treatment,” write the authors. “The addition of new direct-acting agents to the existing pegylated interferon and ribavirin regimen will increase the complexity of HCV therapy for HIV/HCV-coinfected patients…identifying suboptimal adherence using pharmacy refill records might allow clinicians to counsel patients to improve their adherence during therapy.”

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. 

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

eradication

The total elimination of a pathogen, such as a virus, from the body. Eradication can also refer to the complete elimination of a disease from the world.

antiviral

A drug that acts against a virus or viruses.

Many people with HIV also have hepatitis C virus (known as co-infection). Liver disease caused by hepatitis C is now an important cause of serious illness and death in this group. However, antiviral therapy can eradicate hepatitis C infection. Standard treatment consists of pegylated interferon with ribavirin and lasts 48 weeks.

The relationship between the level of adherence and response to hepatitis C therapy in people with co-infection is unclear, and little is known about the risk factors for poor adherence to this treatment. Investigators from the US Department of Veterans Affairs therefore designed a retrospective study involving 333 people with co-infection who started hepatitis C therapy between 2001 and 2006.

Adherence was calculated using pharmacy refill records over twelve-week periods.

Treatment consisted of a once-weekly injection with pegylated interferon and twice-daily oral doses of ribavirin.

The investigators assessed the relationship between the level of adherence to each drug and the chances of achieving an early virological response (EVR; an undetectable hepatitis C viral load twelve weeks after initiating treatment) and a sustained virological response (SVR; eradication of hepatitis C shown by an undetectable viral load 24 weeks after the completion of treatment).

Almost all the participants (98%) were men, 80% were infected with hepatitis C genotypes 1 and 4 (the harder to treat strains of the infection), 44% were African American and a third of the participants had a diagnosis of depression at baseline. Most (90%) were taking HIV therapy.

Mean adherence to pegylated interferon was higher than ribavirin adherence during each twelve-week period. Overall, each twelve-week period saw a 3% decline in adherence to pegylated interferon (from 99 to 88%) and a 4% decline in adherence to ribavirin (from 93 to 78%) (p = 0.04 and p = 0.002 respectively).

Some 6% of the study participants were using methadone and this was associated with lower levels of adherence to both drugs (p = 0.002 and p = 0.04).

“Methadone use might be associated with other factors (e.g. cognitive impairment) that might predispose to decreased adherence or it might be a marker for more severe past narcotic addiction, which may relapse during HCV therapy and result in non-adherence,” suggest the investigators.

An EVR was achieved by 45% of people with genotype 1 or 4 infection.

There was a significant relationship between higher levels of adherence to ribavirin and the chances of achieving an EVR (p = 0.009). There was also a weak association between adherence to pegylated interferon and EVR (p = 0.1).

Just over a quarter (27%) of people with genotype 1 or 4 infection achieved an SVR. Higher levels of adherence to both anti-hepatitis C drugs during the first 36 weeks of therapy were associated with better chances of achieving an SVR.

“These results demonstrate the need to emphasize antiviral adherence throughout the course of HCV therapy,” comment the authors.

“This analysis demonstrated that among HIV/HCV-coinfected patients higher levels of adherence to interferon and ribavirin were associated with higher rates of EVR and SVR,” the researchers conclude, “Future studies should examine additional risk factors for non-adherence and evaluate interventions to maximize adherence to HCV therapy in this population.”

References

Lo Re V et al. Adherence to hepatitis C virus therapy in HIV/hepatitis C-coinfected patients. AIDS Behav, online edition. DOI 10.1007/s10461-012-0288-9, 2012.