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JAMA. 2015 Mar 24-31;313(12):1232-9. doi: 10.1001/jama.2015.1373.

Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection.

Author information

1
Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland3Gilead Sciences Inc, F.
2
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
3
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland5Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc (formerly SAIC-Frederick, Inc), Frederick Nationa.
4
Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
5
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
6
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland6Department of Microbiology and Immunology, Medical University of South Carolina College of Medicine, Charleston.
7
Institute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe University, Frankfurt, Germany.
8
Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore5Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc (formerly SAIC-Frederick, Inc), Frederick National Laborato.
9
Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore.
10
Unity Health Care Inc, Washington, DC.
11
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
12
Family and Medical Counseling Services, Washington, DC.
13
Department of Pathology, National Cancer Institute, Rockville, Maryland.
14
Center for Interventional Oncology, Radiology and Imaging Sciences, NIH Clinical Center and National Cancer Institute, Bethesda, Maryland.
15
Gilead Sciences Inc, Foster City, California.

Abstract

IMPORTANCE:

There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV).

OBJECTIVE:

To evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir.

DESIGN, SETTING, AND PARTICIPANTS:

Open-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed.

INTERVENTIONS:

Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks.

MAIN OUTCOMES AND MEASURES:

The primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment.

RESULTS:

Forty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug.

CONCLUSIONS AND RELEVANCE:

In this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier:NCT01878799.

PMID:
25706232
DOI:
10.1001/jama.2015.1373
[Indexed for MEDLINE]

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