Twice-weekly pegylated interferon improved early treatment responses in co-infected patients

Twice weekly dosing of pegylated interferon improved early response rates to hepatitis C therapy in a small study of co-infected HIV-positive patients, US investigators report in the online edition of AIDS.

Especially impressive results were seen in African-American patients.

Liver disease caused by hepatitis C is a major cause of illness and death in co-infected patients.

Treatment for hepatitis C is available. Lasting for 48 weeks, it consists of a once-weekly injection of pegylated interferon, which is taken in combination with daily oral ribavirin, dosed according to a patient’s weight. Only a minority of co-infected patients who receive therapy during the chronic phase respond to therapy and new treatment strategies are needed.

Suppression of hepatitis C viral load in the first weeks of treatment is predictive of longer-term outcomes. Investigators therefore wanted to see if providing biweekly doses of pegylated interferon during the first four weeks improved early and longer-term responses.

Their small, randomised study involved 19 co-infected patients. All were infected with hepatitis C genotype 1.

Treatment was provided for 48 weeks and all the patients received weight-based doses of ribavirin.

Patients in the treatment arm were given twice-weekly 180 µg doses of pegylated interferon for the first four weeks, and then switched to once-weekly dosing. Those in the control arm received a once weekly 180 µg dose of pegylated interferon for the duration of the study.

Patients were monitored on seven occasions during the first two weeks of treatment (day 0, 3, 6, 6, 7, 10 and 14), and then on day 21, 28, 42, 56. After this time point, the monitoring was conducted every four weeks until week 72.

African-Americans have a poorer response to hepatitis C treatment than Caucasians, and the investigators were therefore especially eager to see what impact the experimental dose had in this group.

Most (84%) of the patients were male and 54% were African American, and their median CD4 cell count was 483 cells/mm³. Two patients in each arm withdrew from the study because of side-effects, but all received a minimum of three weeks of therapy.

After seven days of treatment, patients who received the experimental dose had a significantly lower hepatitis C viral load than those given the standard dose (median, 3.61 copies/log₁₀ ml vs. 5.59 copies/log₁₀ ml; p = 0.032).

Moreover, a higher proportion of patients receiving biweekly pegylated interferon had a 2 log or greater drop in hepatitis C viral load at week 2, week 4 and week 12  (44% vs. O%; 63% vs. 40% and 71% vs. 50% respectively).

A rapid response to hepatitis C treatment (undetectable viral load after four weeks) was observed in 63% of patients on twice-weekly interferon and 30% of individuals receiving the standard dose. This difference was still present after twelve weeks (63% vs. 44%).

However, at the end of treatment comparable proportions of patients in the two study arms had an undetectable hepatitis C viral load (57% vs. 63%).

Treatment is considered to have achieved a cure if a patient has an undetectable hepatitis C viral load six months after completing therapy (sustained virological response). A total of 57% of patients who received the experimental dose of pegylated interferon had this outcome compared to 50% of individuals who received the drug once a week.

A sub-group analysis showed that the experimental dose was associated with favourable early outcomes  - a 2 log drop in viral load at week 2 and week 4 (60% vs. 0% and 75% vs. 0%; p < 0.05) -  in African Americans. 

Higher trough levels of pegylated interferon were seen in patients who received the twice-weekly dose (p = 0.011).

In addition, patients who received the experimental dose normalised their liver function faster than patients treated with once-weekly interferon. ALT levels remained significantly lower in the patients dosed twice weekly at the end of the study.

Increased frequency of pegylated interferon during the first four weeks of treatment did not increase the risk of side-effects.

“While both groups experienced adverse events commonly associated with interferon-based therapy, the investigational group did not demonstrate significantly more toxicities, which suggests that the biweekly therapy is safe and as equally well tolerated as standard therapy,” comment the investigators.

They conclude, “the results of this pilot study show promise for a more effective therapy particularly for HIV/HCV genotype-1 co-infected African Americans.”