Treating patients co-infected with genotype-1 chronic hepatitis C virus and HIV

Janssen Infectious Diseases-Diagnostics BVBA (Janssen) today presented results from a new phase 2 study which shows that an INCIVO® (telaprevir)-based regimen was effective in achieving a sustained virological response at 24 weeks (SVR24) in patients co-infected with both genotype-1 chronic hepatitis C virus (HCV) and HIV (HCV/HIV) compared to patients receiving a placebo with the standard HCV treatment, peginterferon alfa and ribavirin (74% versus 45%).(1)

An estimated 130 to 210 million people are infected with HCV worldwide,(2) with HCV/HIV co-infections averaging about 40% of HCV patients in Europe.(3) People co-infected with HCV/HIV have more rapid fibrosis progression and liver disease than patients with HCV alone.(3) Chronic HCV infections can lead to end-stage liver disease, which is a major cause of death in HCV/HIV co-infected patients.(3) Despite the added health consequences of co-infection, only a small proportion of HCV/HIV co-infected patients receive treatment for their hepatitis.(3)

“The new data further demonstrate the potential efficacy and safety of telaprevir when used in combination with peginterferon alfa and ribavirin in HCV/HIV co-infected patients. New effective treatment regimens are particularly important for this patient group due to their high risk of rapidly developing liver complications,” said investigator, Kenneth E. Sherman MD, of the University of Cincinnati College of Medicine.

The phase 2 study was a two-part randomised, double-blind, placebo-controlled, parallel-group, trial of telaprevir with a standard HCV treatment combination of peginterferon alfa and ribavirin (PR) in previously untreated patients with genotype-1 chronic HCV/HIV co-infection. The study treated a total of 60 HCV/HIV co-infected patients who did or did not receive a concomitant stable antiretroviral therapy (ART) regimen.(1)

During the study, no patients receiving a telaprevir-based regimen experienced HIV RNA breakthroughs and their CD4 T-cell count percentage remained unchanged.(1)

The safety and tolerability of a telaprevir-based regimen for treating HCV in HCV/HIV co-infected patients were comparable to that previously observed in HCV mono-infected patients.(1) Adverse events that occurred more frequently (>10% difference) in HCV/HIV co-infected patients receiving telaprevir and PR compared to HCV/HIV co-infected patients taking PR alone included pruritus (itchiness), headache, nausea, rash and dizziness.(1)

“Now that ART for people living with HIV has improved so vastly over the years in controlling their HIV, it has become increasingly important to address the consequences of chronic HCV infection in patients co-infected with HCV/HIV. Janssen remains committed to addressing the unmet needs of patients and increasing the availability of new treatment options for patient groups who have been largely underserved until now”, said Alessandra Baldini, Medical Affairs Director, Janssen.

Additional telaprevir data being presented at AASLD (http://www.aasld.org/lm2012)includes:

• Non-inferior SVR rates in previously untreated genotype-1 HCV patients receiving a telaprevir-based regimen twice-daily versus every eight hours.(4) Abstract (Final ID: LB-8)
• Telaprevir Global Early Access Programme efficacy and safety data regarding treatment among genotype-1 HCV patients with severe fibrosis or compensated cirrhosis.(5) Abstract (Final ID: LB-15)
• Factors predictive of anaemia development in treatment-experienced patients receiving telaprevir plus PR in the REALIZE trial.(6) Abstract (Final ID: 771)
• Rate of disappearance of telaprevir-resistant variants using clonal and population sequence data from Phase 3 studies.(7) Abstract (Final ID: 756)
• Evaluation of liver and plasma HCV RNA kinetics and telaprevir levels in genotype-1 HCV patients treated with telaprevir using serial fine needle aspirates.(8) Abstract (Final ID: 215)
• Deep sequencing of the HCV NS3/4A region confirms low prevalence of telaprevir-resistant variants.(9) Abstract (Final ID: 1091)

1. Sulkowski MS, Sherman KE, Soriano V, et al. Telaprevir in Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Co-infected Patients: SVR24 Final Study Results. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract (Final ID: 54).
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology. 2011; 55: 245–264.
3. WHO EUROPE. Management of Hepatitis C and HIV co-infection – Clinical protocol for the WHO European Region. Available at: http://www.euro.who.int/data/assets/pdf_file/0008/78146/E90840_Chapter_6.pdf. Last accessed September 12, 2012.
4. Buti M, Agarwal K, Horsmans Y, et al. OPTIMIZE Trial: Non-inferiority of twice-daily telaprevir versus administration of every 8 hours in treatment-naïve, genotype 1 HCV infected patients. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract (Final ID: LB-8)
5. Colombo M et al. Treatment of Hepatitis C Genotype 1 Patients with Severe Fibrosis or Compensated Cirrhosis: The International Telaprevir Early Access Program. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract (Final ID: LB-15)
6. Zeuzem S, DeMasi R, Baldini A, et al. Factors predictive of anemia development in treatment-experienced patients receiving telaprevir (T;TVR) plus peginterferon/ribavirin (PR) in the REALIZE trial. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract (Final ID: 771).
7. Sullivan J, De Meyer S, Haseltine E, et al. Rate of disappearance of telaprevir resistant variants using clonal and population sequence data from Phase 3 studies. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract (Final ID: 756).
8. Talal A, Dimova R, Zhang E, et al. Evaluation of Liver And Plasma HCV RNA Kinetics And Telaprevir Levels In Genotype 1 HCV Patients Treated With Telaprevir (TVR) Using Serial Fine Needle Aspirates (FNA). 2012. American Association for the Study of Liver Diseases (AASLD) Abstract (Final ID: 215).
9. Dierynck I, De Meyer S, Thys K, et al. Deep Sequencing of the HCV NS3/4A Region Confirms Low Prevalence of Telaprevir-resistant Variants Both at Baseline and End of Study. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract (Final ID: 1091).