Extended peginterferon alfa-2a therapy for >1 year is possible in most patients with hepatitis D virus (HDV) infection, but with combined use of tenofovir disoproxil fumarate (TDF) not demonstrating a significant effect on end-of-treatment response rates. Two parallel, investigator-initiated, multicenter, double-blind, randomized, placebo-controlled, phase 2 trials (Hep-Net International Delta Hepatitis Intervention Trial [HIDIT] I and II; ClinicalTrials.gov identifiers: NCT00932971 and NCT01088659) were conducted at 14 study sites in Germany, Greece, Romania, and Turkey. Results of the analyses were published in the Lancet Infectious Diseases.
The investigators sought to evaluate whether prolonged treatment of HDV for 96 weeks with peginterferon would increase HDV RNA response rates and reduce posttreatment relapses among patients with HDV infection. They also assessed whether combination treatment with TDF would increase HDV RNA suppression.
Patients ≥18 years of age with chronic HDV infection and compensated liver disease were eligible for study inclusion. All participants were HBsAg-positive for ≥7 months, anti-HDV-positive for ≥3 months, and HDV-RNA-positive at their local laboratory at the initial screening visit. Patients were randomly assigned, in a 1:1 ratio, to receive peginterferon alfa-2a 180 µg weekly plus either TDF 300 mg once daily or placebo for 96 weeks.
The primary study endpoint was the percentage of patients with undetectable HDV RNA at the conclusion of the treatment, per intention-to-treat assessment. Between June 24, 2009, and February 28, 2011, a total of 59 HDV-RNA-positive patients received peginterferon alfa-2a plus TDF and 61 received peginterferon alfa-2a plus placebo. Of the 120 patients enrolled, 48 also had cirrhosis (23 participants in the peginterferon-alfa-2a-plus-TDF group and 25 participants in the peginterferon-alfa-2a-plus-placebo group).
The primary endpoint was attained in 48% (28 of 59) of those in the peginterferon-alfa-2a-plus-TDF group and 33% (20 of 61) of those in the peginterferon-alfa-2a-plus-placebo group (odds ratio, 1.84; 95% CI, 0.86-3.91; P =.12). Overall, 944 adverse events were reported (459 in the peginterferon-alfa-2a-plus-TDF group and 485 in the peginterferon-alfa-2a-plus-placebo group). The most common adverse events were hematologic, behavioral (eg, fatigue), musculoskeletal, influenza like syndromes, and psychiatric complaints.
The investigators concluded that the addition of TDF was not associated with any significant improvement in HDV RNA response rates at the end of the treatment period. The findings from this study underscore the need for alternative therapeutic options in patients with HDV infection.
Wedemeyer H, Yurdaydin C, Hardtke S, et al; HIDIT-II study team. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial. Lancet Infect Dis. 2019;19(3):275-286.