Response to HCV Treatment: Prognostic Factors

Because of the limited efficacy and considerable side effects of HCV treatment, clinicians and their patients need to thoroughly assess and discuss risks and benefits of HCV treatment. The decision-making process should take into account individual prognostic factors.

HCV treatment is less effective for coinfected people than for those with HCV alone. In three studies (AACTG 5071, APRICOT, and RIBAVIC), however, CD4 cell count was not associated with response to treatment (Table 4). The sample size of people with CD4 cell counts of less than 200/mL in each study was small, and most study participants were taking HAART prior to and during HCV treatment.87-93 The studies did not report an increased incidence of opportunistic infections among participants who had CD4 cell counts of less than 200/mL.87-89

Other factors have a significant effect on response to treatment, regardless of HIV status. The HCV genotype is a major prognostic factor. At least six different HCV genotypes have been identified. In the United States, most HCV infections are genotype 1.94 Genotypes 1 and 4 are less sensitive to treatment than are genotypes 2 and 3.87-89,95,96

Although HCV viral load is not strongly associated with disease progression (unlike HIV viral load), HCV viral load is a prognostic factor for response to therapy, particularly in genotype 1 and genotype 4 infections. People with a baseline HCV RNA of more than 800,000 per MIU are less likely to respond to HCV treatment than are people with lower HCV RNA levels.87-89,95,96 HCV RNA levels are usually significantly higher in coinfected people than in people with HCV monoinfection.97-99

In HCV monoinfection treatment trials, response rates among African-Americans—among whom both HIV and HCV are disproportionately prevalent—have been significantly lower than response rates among non-Hispanic whites.6,100-104 The reasons for this disparity are unclear. Data on response rates to HCV treatment among coinfected African-Americans are limited; only one pivotal HCV treatment trial in coinfected persons has been conducted solely in the United States (ACTG 5071), and race and ethnicity were not predictive of response to HCV treatment in that study.88 HCV genotype was the most significant predictive factor for response to HCV treatment in the trial; the results could have masked the effect of race, because genotype 1 infections are more likely among African-Americans than among people of other ethnicities.94,101,105 The predominance of HCV 1 genotype among African-Americans has been cited as a factor in decreased response rates to HCV treatment.

Data from HCV monoinfection treatment trials suggest that lifetime alcohol consumption and alcohol intake during HCV treatment are associated with poorer response rates. The treatment regimen in the studies was standard interferon monotherapy, however, and information on adherence to HCV therapy was not included.106-109 A more recent study using standard interferon plus ribavirin reported that alcohol intake prior to or during treatment did not influence response to HCV treatment.110 Many clinicians withhold HCV treatment until patients have been abstinent from alcohol for 3 to 6 months, but some treat on a case-by-case basis.56,111 Because alcohol accelerates HCV disease progression, clinicians need to work with their patients to help them reduce or eliminate alcohol consumption as part of HCV care, whether or not the patients are candidates for HCV treatment.