Sofosbuvir-Containing Regimens Without Interferon For Treatment of Acute Hepatitis C Virus (HCV) Infection
Summary
Early identification of acute HCV infection is essential to prevent chronic infections and the long-term liver disease complications that may occur. Early identification and treatment of HCV during the acute phase can result in significantly higher response rates with shorter durations of therapy. Pegylated-interferon alfa (PEG-IFN) was the typical treatment for HCV infection. Participants subcutaneously inject PEG-IFN where the average duration of treatment was approximately 20 weeks. With the advancement of direct-acting antivirals (DAAs), it was possible to see if a new DAA might be non-inferior compared to (PEG-IFN). The study was designed to see if a fixed-dose combination tablet can replace the old HCV treatments by being more effective, safer and better tolerated in HIV-infected participants with new HCV infection. The study was a Phase I, open-label, two cohort clinical trial, in which 44 acutely HCV-infected HIV-1 positive participants were enrolled. Participants in each cohort were evaluated in two steps: on treatment (Step 1) and follow-up after discontinuing study treatment (Step 2). The cohorts were enrolled sequentially. Participants in Cohort 1 were enrolled and administered oral Sofosbuvir (SOF) in combination with weight-based ribavirin (RBV). Participants in Cohort 2 were enrolled and administered an oral fixed dose combination of Ledipasvir/Sofosbuvir (LDV/SOF).
Timeline
- Start
- 2014-05-30
- Primary completion
- 2017-02-28
- Completion
- 2017-05-09
Outcome
Mixed primary results
paper All participants (100%) achieved the primary outcome of a sustained virologic response 12 weeks after the date of the last dose of study treatment PMID 31220220 ↗
paper achieving non-inferiority versus the 60% historic benchmark. PMID 31220220 ↗
paper Ten participants (59%) achieved the primary outcome of SVR12 (90% confidence interval, 36%-78%), failing to establish noninferiority. PMID 28329053 ↗
Publications
- Naggie S, Fierer DS, Hughes MD, Kim AY, Luetkemeyer A, Vu V, Roa J, Rwema S, Brainard DM, McHutchison JG, Peters MG, Kiser JJ, Marks KM, Chung RT; Acquired Immunodeficiency Syndrome Clinical Trials Group (ACTG) A5327 Study Team. Ledipasvir/Sofosbuvir for 8 Weeks to Treat Acute Hepatitis C Virus Infections in Men With Human Immunodeficiency Virus Infections: Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals. Clin Infect Dis. 2019 Jul 18;69(3):514-522. doi: 10.1093/cid/ciy913.
- Naggie S, Marks KM, Hughes M, Fierer DS, Macbrayne C, Kim A, Hollabaugh K, Roa J, Symonds B, Brainard DM, McHutchison JG, Peters MG, Kiser JJ, Chung R; AIDS Clinical Trials Group (ACTG) A5327 Study Team. Sofosbuvir Plus Ribavirin Without Interferon for Treatment of Acute Hepatitis C Virus Infection in HIV-1-Infected Individuals: SWIFT-C. Clin Infect Dis. 2017 Apr 15;64(8):1035-1042. doi: 10.1093/cid/cix025.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Ledipasvir | Small molecule | 90 mg | Oral |
| Subject | Ribavirin | Small molecule | 400 mg | Oral |
| Subject | Ribavirin | Small molecule | 600 mg | Oral |
| Subject | Sofosbuvir | Small molecule | 400 mg | Oral |