Interferon-free treatment with sofosbuvir/daclatasvir achieves sustained virologic response in 100% of HIV/hepatitis C virus-coinfected patients with advanced liver disease.

Abstract

AIM:

We aimed to investigate the safety and efficacy of interferon (IFN) and ribavirin (RBV)-free therapy with sofosbuvir along with daclatasvir (SOF/DCV) in HIV/hepatitis C virus (HCV)-coinfected patients (HIV/HCV), who have an urgent need for effective antiviral therapy. We also assessed its impact on liver stiffness and liver enzymes.

DESIGN:

Thirty-one patients thoroughly documented HIV/HCV with advanced liver disease (advanced liver fibrosis and/or portal hypertension) who were treated with SOF/DCV were retrospectively studied.

METHODS:

The following treatment durations were applied: HCV-genotype (HCV-GT)1/4 without cirrhosis: 12 weeks; HCV-GT1/4 with cirrhosis: 24 weeks; HCV-GT3: 24 weeks; if HCV-RNA was detectable 4 weeks before the end of treatment, treatment was extended by 4 weeks at a time.

RESULTS:

Fifty-two percent of patients were treatment-experienced. The majority of patients had HCV-GT1 (68%), whereas HCV-GT3 and HCV-GT4 were observed in 23 and 10% of patients, respectively. Ninety-four percent had liver stiffness greater than 9.5 kPa or METAVIR fibrosis stage higher than F2 and 45% had liver stiffness above 12.5 kPa or METAVIR F4. Portal hypertension (HVPG ≥6 mmHg) and clinically significant portal hypertension (HVPG ≥10 mmHg) were observed in 67% (18/27) and 26% (7/27) of patients, respectively. Sustained virologic response 12 weeks after the end of treatment (SVR12) was achieved in 100% (31/31). Treatment with SOF/DCV was generally well tolerated and there were no treatment discontinuations. HCV eradication improved liver stiffness from 11.8 [interquartile range (IQR): 11.5 kPa] to 6.9 (IQR: 8.2) kPa [median change: -3.6 (IQR:5.2) kPa; P < 0.001] and decreased liver enzymes. The mean time period between treatment initiation and follow-up liver stiffness measurement was 32.7 ± 1.2 weeks.

CONCLUSION:

IFN- and RBV-free treatment with SOF/DCV was well tolerated and achieved SVR12 in all HIV/HCV with advanced liver disease. It also significantly improved liver stiffness, suggesting anti-fibrotic and anti-portal hypertensive effects.

• Authors: Mattias Mandorfer, Philipp Schwabl, Sebastian Steiner, Bernhard Scheiner, David Chromy, Theresa Bucsics, Albert Friedrich Stättermayer, Maximilian Christopher Aichelburg, Katharina Grabmeier-Pfistershammer, Michael Trauner, Thomas Reiberger, Markus Peck-Radosavljevic
• Journal: AIDS (London, England) (AIDS) Vol. 30 Issue 7 Pg. 1039-47 (Apr 24 2016) ISSN: 1473-5571 [Electronic] England
• PMID: 26760453 (Publication Type: Clinical Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Pyrrolidines
• Valine
• daclatasvir
• Sofosbuvir

Topics

• Antiviral Agents (adverse effects, therapeutic use)
• Carbamates
• Coinfection (drug therapy)
• Drug Therapy, Combination (adverse effects, methods)
• Female
• HIV Infections (complications)
• Hepatitis C, Chronic (complications, drug therapy, pathology)
• Humans
• Imidazoles (adverse effects, therapeutic use)
• Male
• Middle Aged
• Pyrrolidines
• Retrospective Studies
• Sofosbuvir (adverse effects, therapeutic use)
• Treatment Outcome
• Valine (analogs & derivatives)