Virological response to hepatitis C therapy after four weeks appears to predict who will have a successful response to a full course of treatment in HIV-positive people coinfected with hepatitis C genotypes 1 or 3, according to findings from two studies presented last week at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver.
24 week treatment adequate for most rapid responders with genotype 3
Currently, a 24 week course of pegylated interferon (Pegasys, Peg-Intron or Viraferon Peg) plus ribavirin is the recommended standard treatment for patients with genotype 2 or 3 hepatitis C virus (HCV) infection; 48 weeks is recommended for genotype 1. However, because relapse is more common in coinfected individuals, some research - as well as recent guidelines - suggests that this population may benefit from longer therapy.
Manel Crespo and colleagues from Barcelona reported on treatment of genotype 2 or 3 HCV in people with HIV. The researchers conducted a retrospective review of data from a subset of 42 coinfected patients enrolled in an open-label randomised trial. Participants were treated with either conventional interferon (3 MIU three times weekly) or Peg-Intron brand pegylated interferon (1.5 mcg/kg once weekly) plus ribavirin (800mg daily) for 24 weeks.
Participants were mostly men (86%) with a median age of 38.6 years; 83% had a history of injecting drug use. All but one of the 42 patients had genotype 3 HCV (the other had genotype 2), and 76% had HCV viral loads above 800,000 IU/ml. At enrolment, patients had a median CD4 cell count of 505 cells/mm3, 81% had undetectable HIV viral load (below 50 copies/ml), and 89% were taking HAART.
Using an intent-to-treat analysis, end-of-treatment response (ETR) rates at 24 weeks were 67.0% in the conventional interferon arm and 76.0% in the pegylated interferon group. Sustained virological response (SVR) rates, measured 24 weeks after the completion of therapy, were 43.0% and 71.0%, respectively (p = 0.06).
Week 4 HCV RNA measurements were available for 36 participants, 20 of whom (55.5%) had undetectable HCV viral load (below 100 IU/mL) at this time. Both ETR and SVR rates were higher among patients who experienced rapid virological response (RVR) by week 4. Among patients who experienced RVR, 95.0% achieved ETR and 90.0% achieved SVR. Among those without RVR, the corresponding ETR and SVR rates were 69.0% and 37.0%. Those without RVR had a relapse rate of 45.5%, compared with just 5.3% among rapid responders (p = 0.05).
These results suggest that 24 weeks of pegylated interferon plus ribavirin is adequate for a majority of coinfected individuals with genotype 3 HCV, particularly those who experience rapid response to therapy; it is harder to draw conclusions regarding genotype 2, since there was only one patient in this category. This contradicts earlier data suggesting that coinfected patients with genotypes 2 or 3 might benefit from 48 weeks of treatment.
The researchers concluded that RVR at week 4 appears to be “a useful tool to individually adjust the duration of treatment” in coinfected patients with genotypes 2 or 3, since rapid responders achieved high SVR and low relapse rates.
Rapid response also predicts treatment success in genotype 1 patients
Based on data from the APRICOT study, Douglas Dieterich and colleagues reported in a poster presentation that rapid virological response at four weeks also predicted SVR in coinfected patients with genotype 1.
The APRICOT study (reported at the 2004 Retrovirus conference) and in the July 29, 2004 edition of the New England Journal of Medicine) included 860 HIV/HCV coinfected participants randomly assigned to receive standard interferon plus ribavirin, Pegasys brand pegylated interferon plus placebo, or Pegasys plus ribavirin for 48 weeks. Overall SVR rates in the three arms were 40%, 20%, and 12%, respectively (29%, 14%, and 7%, respectively, for genotype 1 patients).
The current study analysed data from the 176 genotype 1 patients treated with Pegasys plus ribavirin. Whilst the overall SVR rate was 29% in this group, responses differed by baseline HCV RNA level: those with low baseline HCV viral load (800,000 IU/ml or less) had an SVR rate of 61%, compared with 18% among those with high baseline HCV viral load.
The likelihood of sustained response also differed on the basis of rapid response at four weeks. Just 13% of the genotype 1 patients in this arm (22 of 176) experienced RVR. Among these, 82% (18 of 22) went on to achieve SVR. Among the participants who experienced RVR, 83% (15 of 18) with low HCV viral load and 75% (3 of 4) with high HCV viral load achieved SVR. The researchers concluded that RVR at week 4 “indicates a high probability of SVR in [genotype 1] patients (~80%) regardless of baseline viral load.”
Prior research has shown that early virological response at week 12 can predict which coinfected patients will ultimately benefit from hepatitis C treatment. Data from these two studies suggest that this time frame may be shortened even further, allowing patients who are unlikely to achieve SVR to forego the side effects and expense of longer therapy.
Crespo M et al. Utility of the early viral response to individually-adjust the duration of treatment for chronic hepatitis C, genotype 2 or 3, in HIV-coinfected patients. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 81, 2006.
Dieterich D et al. Sustained virologic response (SVR) in HIV-HCV co-infected patients with HCV genotype 1(G1) infection who have a rapid virological response (RVR) at week 4 of treatment with peginterferon alfa-2a (40KD) (PEG IFN a-2a, Pegasys) plus ribavirin (RBV, Copegus): AIDS Pegasys Ribavirin International Co-infection Trial (APRICOT). Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 856, 2006.