By Liz Highleyman

Standard therapy for chronic hepatitis C virus (HCV) infection in HIV negative people is 24 weeks of pegylated interferon plus weight-adjusted ribavirin for those with HCV genotypes 2 or 3, and 48 weeks for those with harder-to-treat genotypes 1 or 4.

Current guidelines indicate that HIV positive patients should receive combination anti-HCV therapy for 48 weeks regardless of HCV genotype. But coinfected individuals with genotypes 2 or 3 can achieve good outcomes with the shorter 24-week course, according to data presented at the annual Digestive Disease Week (DDW 2009) meeting this week in Chicago.

Jean-Jacques Gonvers and colleagues from Switzerland evaluated the antiviral efficacy of pegylated interferon plus ribavirin in HIV-HCV coinfected and HCV monoinfected patients and assessed whether 24 weeks of therapy would suffice for coinfected patients with favorable HCV genotypes 2 or 3. Secondary analyses looked at treatment side effects and speed of HCV viral load decline as a predictor of sustained virological response (SVR), or continued undetectable HCV RNA 24 weeks after completion of therapy.

The study included 85 HCV monoinfected participants (38 with genotypes 1, 4, or 5; 47 with genotypes 2 or 3) and 47 HIV-HCV coinfected patients (23 with genotypes 1, 4, or 5; 24 with genotypes 2 or 3). About 60% of the coinfected participants were on HAART.

Patients with genotypes 1, 4, or 5 were treated for 48 weeks with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day ribavirin, with doses adjusted according to body weight. Patients with genotypes 2 or 3 received the same dose of Pegasys plus 800 mg/day ribavirin (regardless of weight) for 24 weeks.

Results

In an intention-to-treat analysis of participants with genotypes 1, 4, or 5, the SVR rate was more that 4-fold higher for HCV monoinfected patients (58%) compared with HIV-HCV coinfected patients (13%)(P = 0.001).

Looking at patients with genotypes 2 or 3, 70% of HCV monoinfected patients and 67% of HIV-HCV coinfected patients achieved SVR, not a significant difference (P = 0.973).

Undetectable HCV RNA at week 4 -- known as rapid virological response (RVR) -- had a positive predictive value (PPV) for SVR:

.78 for HCV monoinfected patients with genotypes 1, 4, or 5;

.81 for HCV monoinfected patients with genotypes 2 or 3;

.76 for HIV-HCV coinfected patients with genotypes 2 or 3.

22 patients (36%) with genotypes 1, 4, or 5 did not complete the study for various reasons (lack of response at week 12, withdrawal of consent, adverse events, death) compared with 12 patients (17%) with genotypes 2 or 3.

These findings led the researchers to conclude, "Genotypes 2 and 3 predict the likelihood of SVR in [HCV] mono- and in coinfected patients."

"In coinfected patients with genotypes 2 and 3, a 6-month treatment has the same efficacy as in monoinfected patients," they continued. "Undetectable HCV RNA at week 4 has a good positive predictive value of SVR."

Finally, they recommended, "Aggressive treatment of adverse effects to avoid withdrawal or treatment stop is crucial."

Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; University of Basle, Basle, Switzerland; University of Zurich, Zurich, Switzerland; Hospital of La Chaux-de-Fonds, La Chaux-de-Fonds, Switzerland; Hospital of Lugano, Lugano, Switzerland; Private Practice, Winthertur, Switzerland.

6/5/09

Reference
JJ Gonvers, MH Heim, M Cavassini, and others. In HIV-HCV Co-Infected Patients with HCV Genotype 2 or 3 Infection a 6-Month Treatment with Peginterferon Alpha Plus Ribavirin Has the Same Efficacy As in Mono-Infected Patients. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract S2071.