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What Factors Influence Adherence to Treatment for Hepatitis C?


Efficacy, or likelihood of achieving sustained virological response, was the most important factor influencing adherence among people considering treatment for chronic hepatitis C, according to a recent survey. Other factors affecting adherence included depression, flu-like symptoms days, lost work days, hair loss, and type of interferon injection equipment.

Pegyalted interferon plus ribavirin for chronic hepatitis C virus (HCV) infection is a challenging treatment that requires injections and can cause difficult side effects, both of which can discourage optimal adherence.

There have been few studies that measure patient adherence to hepatitis C treatment. These studies of pegylated interferon/ribavirin combination therapy showed that adherence was generally high at the start of treatment (70%-98%), was higher for interferon than for ribavirin, and decreased over time for both drugs. Studies have produced mixed findings about the correlation between adherence and achieving sustained virological response (SVR). One such study found that 63% of people with HCV genotype 1 who were > 80% adherent to pegylated interferon and ribavirin achieved SVR, compared with only 34% of people whose adherence rates were 80% or lower. Another study, however, showed no correlation between SVR rates and different levels of adherence.

Increasing rates of non-adherence over time suggest that achieving SVR may not be the only important treatment factor taken into account by people with HCV. Skipping doses may indicate that patients are willing to reduce the likelihood of achieving sustained response in order to avoid treatment side effects.

With the introduction of the direct-acting antivirals boceprevir (Victrelis) and telaprevir (Incivek), and the possibility of developing HCV drug resistance, adherence is likely to become a more important consideration. Understanding which treatment factors matter most to patients -- particularly those side effects that lead to missed doses -- can help inform the design of patient education programs, side effect management, and development of future medications.

In the September 2011 Journal of Viral Hepatitis, A. Brett Hauber from RTI International and colleagues described their analysis of responses of 150 participants with chronic hepatitis C who rated treatment factors that would make them more or less likely to skip or miss medication doses.


Participants were recruited from an online chronic illness panel and the survey was administered in August 2008. The 150 participants were split evenly between men and women, most (86%) were white, and the mean age was 48 years. In terms of HCV treatment history, 47% had never been on treatment, 10% were receiving treatment for the first time, and 43% were receiving treatment for at least the second time or had received treatment previously.

The researchers utilized choice-format conjoint analysis methods for their study. Choice-format conjoint analysis is a way of eliciting trade-offs to quantify the relative importance people assign to various factors and outcomes, such as treatment efficacy, safety, and mode of administration.

The researchers identified 7 attributes to describe specific treatment alternatives:

  • Efficacy: the probability of achieving SVR (40%-70%);
  • Injection frequency (once per week to once every 4 weeks);
  • Duration of flu-like symptoms after each injection (1-3 days);
  • Type of injection device (vial and syringe or a pen injection device);
  • Average number of work days missed each week due to treatment side effects (0-2 days);
  • Alopecia: probability of hair thinning while on treatment (0%-40%);
  • Depression: probability of developing clinical depression while on treatment (5%-25%).

The researchers also include 3 specific adherence questions on the survey to assess how often the participants thought they might miss or skip doses based on treatment regimens with various attributes.


  • The impact of flu-like symptoms was best expressed as the number of "flu days" each month -- the product of injection frequency and duration of symptoms after each injection.
  • Over the range of levels of each factor, treatment efficacy was rated as the most important factor affecting adherence.
  • In order of importance, the remaining factors were ranked as follows:
    • Depression;
    • Flu days;
    • Lost work days;
    • Alopecia;
    • Injection device.
  • Efficacy was significantly more important than any other factor.
  • Depression, flu days, and lost work days were significantly more important than alopecia and injection device.
  • Among the treatment-experienced participants, 31 (91%) said that their hair grew back after their treatment was finished.
  • 39 treatment-experienced participants (68%) said that they felt depressed while on treatment.
  • Participants who had received HCV therapy before were less likely than previously untreated people to say that treatment attributes would affect the probability of their skipping or missing doses.
  • The only treatment factor likely to increase the probability of skipping or missing doses was a greater number of flu days, either due to more injections or more days of flu-like symptoms after each injection.

“The results of this study indicate that sustained viral response was the most important attribute of a drug treatment to patients," the researchers wrote. “However, the results of the choice-format conjoint survey also indicate that patients were willing to accept decreases in the probability of achieving sustained viral response to reduce side effects of treatment.”

Depression and days with flu-like symptoms were important side effects to people with hepatitis C, while temporary hair loss was the least important of the side effects included in the analysis.

In summary, the researchers concluded, “the results of our analyses have shown that, although efficacy is clearly the most important treatment attribute, other attributes related to treatment side effects are also important and may reduce adherence to current treatments. Because adherence to therapy, especially in those with genotype 1 HCV infections, has been shown to be important for achieving a sustained viral response, new treatment regimens that reduce side effects relative to current treatments might result in higher adherence rates and better clinical effectiveness.”

Investigator affiliations: RTI International, Research Triangle Park, NC. Human Genome Sciences, Inc., Rockville, MD, and Novartis Pharma AG, Basel, Switzerland.



A Brett Hauber, AF Mohamed, C Beam, et al. J. Patient preferences and assessment of likely adherence to hepatitis C virus treatment. Journal of Viral Hepatitis18(9): 619-627 (abstract). September 2011.