Sofosbuvir Plus Ribavirin Without Interferon for Treatment of Acute Hepatitis C Virus Infection in HIV-1-Infected Individuals: SWIFT-C

Abstract

Background: Historically, acute hepatitis C virus (HCV) infection was treated with shorter durations of interferon-containing therapies. In the era of direct-acting antivirals (DAAs), it is unclear whether the efficacy of treatment achieved in chronic infection can be maintained with abbreviated courses of therapy during the acute phase.

Methods: The sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals (SWIFT-C) is an open-label, 2-cohort clinical trial in which the first cohort assessed for the safety and efficacy of 12 weeks of sofosbuvir plus ribavirin for the treatment of acute HCV infection in participants with chronic human immunodeficiency virus type 1 (HIV-1) infection. This is a preplanned analysis of the first cohort, which had a planned accrual of 17 participants.

Results: Seventeen men (11 Hispanic, 6 white, median age 45 years) were enrolled. Most (88%) had HCV genotype-1 infection and few (24%) had the favorable IL28B CC genotype. Median baseline HCV RNA was 2 280 000 IU/mL (interquartile range, 272 000-4 230 000). Ten participants (59%) achieved the primary outcome of SVR12 (90% confidence interval, 36%-78%), failing to establish noninferiority. All treatment failures were due to viral relapse (41%). There were no premature treatment discontinuations. The only factor that differed between participants who achieved SVR vs those who relapsed was ribavirin concentration at the end of treatment.

Conclusion: Sofosbuvir-ribavirin for 12 weeks for the treatment of acute HCV genotype-1 infection in HIV-1-infected persons results in a high relapse rate. Preliminary studies of DAA combination therapies suggest improved response rates, although the adequate duration of therapy remains unclear.

Clinical trials registration: NCT02128217.

Keywords: direct-acting antivirals; early infection; hepatitis; human immunodeficiency virus; interferon-free.

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Figures

Figure 1.

SWIFT-C study Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

Figure 2.

Hepatitis C virus (HCV) RNA viral kinetic plots for those who did not achieve sustained virologic response (SVR) 12 (N = 7). HCV RNA (in log10 IU/mL) is shown on the y-axis and study follow-up visits are shown on the x-axis.

Figure 3.

Ribavirin concentrations in participants who achieved sustained virologic response (SVR; black) vs those who experienced viral relapse (gray). Ribavirin concentration (in nanogram per milliliter) is shown on the y-axis and time on study (in weeks) is shown on the x-axis. The median (interquartile range) ribavirin concentration in those who achieved SVR was 2655 (2156–3101) ng/mL vs 1745 (908–2131) ng/mL in those who relapsed, P = .01. Smooth lines of the ribavirin concentrations are shown (dashed for SVR, solid for relapse). Abbreviation: SVR, sustained virologic response.

Figure 4.

Phylogenetic tree of paired hepatitis C virus NS5B sequences for 4 participants with relapse and available sequences pre- and post-therapy.