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.

Abstract

BACKGROUND:

Current guidelines for the management of hepatitis C virus (HCV) infections provide varying recommendations for the optimal treatment of acute HCV infections. There are limited data from small cohort studies to provide guidance on the best approach to treatment of this important patient population.

METHODS:

Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals is an open-label, 2-cohort, Phase 1 clinical trial in which the second cohort assessed the safety and efficacy of 8 weeks of ledipasvir/sofosbuvir for the treatment of acute HCV infections in participants with chronic human immunodeficiency virus (HIV)-1 infections. This final analysis of the second cohort had a planned accrual of 27 participants, based on non-inferiority criteria, compared to the study-defined, historical, sustained virologic response (SVR) of 60% with pegylated-interferon/ribavirin.

RESULTS:

We enrolled 27 men (9 Hispanic; 11 White, non-Hispanic; 5 Black, non-Hispanic; 2 Asian or Pacific Islander; median age 46 years). Most (96%) had HCV genotype-1 infection and 59% had the favorable interleukin 28B CC genotype. The median baseline HCV RNA load was 6.17 log10 IU/mL (interquartile range 4.51 - 6.55). All participants (100%) achieved the primary outcome of a sustained virologic response 12 weeks after the date of the last dose of study treatment (90% confidence interval 90-100%), achieving non-inferiority versus the 60% historic benchmark. No treatment discontinuations occurred.

CONCLUSIONS:

This multicenter clinical trial, investigating 8 weeks of ledipasvir/sofosbuvir for acute HCV infections in men with HIV infections, reports a 100% SVR. This study provides the rationale for larger studies of shortened courses of direct-acting antiviral therapies in persons with HIV infections, including those with high baseline HCV RNA loads.

CLINICAL TRIALS REGISTRATION:

NCT02128217.

• Authors: Susanna Naggie, Daniel S Fierer, Michael D Hughes, Arthur Y Kim, Annie Luetkemeyer, Vincent Vu, Jhoanna Roa, Steve Rwema, Diana M Brainard, John G McHutchison, Marion G Peters, Jennifer J Kiser, Kristen M Marks, Raymond T Chung, Acquired Immunodeficiency Syndrome Clinical Trials Group (ACTG) A5327 Study Team
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 69 Issue 3 Pg. 514-522 (07 18 2019) ISSN: 1537-6591 [Electronic] United States
• PMID: 31220220 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Antiviral Agents
• Benzimidazoles
• Fluorenes
• ledipasvir, sofosbuvir drug combination
• Ribavirin
• Interferons
• Uridine Monophosphate
• Sofosbuvir

Topics

• Acute Disease (therapy)
• Administration, Oral
• Adult
• Antiviral Agents (therapeutic use)
• Benzimidazoles (therapeutic use)
• Cohort Studies
• Drug Administration Schedule
• Fluorenes (therapeutic use)
• HIV Infections (virology)
• Hepacivirus
• Hepatitis C (drug therapy)
• Humans
• Interferons (therapeutic use)
• Male
• Middle Aged
• Ribavirin (therapeutic use)
• Sexual and Gender Minorities
• Sofosbuvir
• Sustained Virologic Response
• Uridine Monophosphate (analogs & derivatives, therapeutic use)
• Viral Load (drug effects)