Investigational Antiviral Offers Benefit in Patients Co-Infected with Hepatitis C, HIV

A novel direct-acting antiviral (DAA) targeting a protein associated with hepatitis C (HCV) also has antiviral activity against HIV-1 and shows benefit in co-infected individuals when added to pegylated interferon and ribavirin treatment (PR), according to a poster presented by Carolyn Luscombe, PhD, and co-investigators at the 2013 annual meeting of the American Association for the Study of Liver Disease (AASLD), held November 1-5, 2013, in Washington, DC.

Luscombe, the development manager of Australia’s Biotron, Ltd., was the lead author of the small phase 2 open-label pilot study, which provided initial evaluation of the safety and tolerability of BIT225 when dosed for 28 days during a longer PR treatment course. Secondary objectives of the pilot study included examining the pharmacokinetics of BIT225 + PR and evaluating the antiviral activity of BIT225 + PR in the subject population, all of whom were HIV-1 and HCV co-infected with HCV genotype 1 (G1) or genotype 3 (G3).

According to the poster authors, the 12 patients had a mean age of 44 and were 75% male and 100% Asian. Four patients had HCV G1a, while 8 had HCV G3. All subjects’ HIV-1 was well controlled, with HIV-1 RNA of less than 40 copies/mL. However, prior treatment status was not reported.

Patients were administered 7 days of weight-based PR dosing before beginning 28 consecutive days of BIT225 treatment. After completion of the BIT225 regimen, PR was continued for up to 44 weeks. Two of the HCV G3 patients withdrew from the study; of the 6 remaining, all had levels of HCV below the lower level of quantitation (LLOQ) at the end of the treatment period.

While examining viral kinetics, the investigators discovered a tri-phasic response to BIT225 with a steep increase in the rate of viral decay with the initiation of BIT225, a small rebound, and a less rapid rate of decay leading to undetectable HCV RNA.

Among the G1a subjects, response varied by genotype. One subject who was homozygous for IL28B had rapid response to PR and HCV RNA below LLOQ by week 8. Another subject withdrew because of treatment intolerance. Two more subjects who were heterozygous for IL28B did not respond to treatment, which was discontinued due to non-efficacy.

The HIV-1 viral load remained below 40 copies/mL in all subjects at all time points throughout the 12 weeks of the study period. The authors asserted that BIT225 had no effect on the efficacy of the variety of antiretroviral therapies that the study subjects reported taking.

Adverse events most commonly reported during the BIT225 administration period included headache and nausea. Drug intolerance was the reason 3 subjects withdrew during the first 14 days of treatment. The investigators reported that further safety and pharmacokinetic data will be presented in a later publication.

The poster authors said that all 6 of the HCV G3 individuals in the study reached undetectable levels of HCV RNA by 12 weeks of treatment, with initiation of BIT225 accelerating the rate of viral decay in the group. According to the authors, the context of the findings involved SVR rates of 68.8% in Thai HCV G3 patients who received PR therapy alone.