Triple Combination Therapy for Hepatitis C with Telaprevir Exhibits Greater Early Antiviral Activity than with Boceprevir

Abstract

Background

Achievement of early viral suppression is important in patients with chronic HCV infection treated with telaprevir (TLV) or boceprevir (BOC) to avoid selection of drug resistance and attain cure. No head-to-head studies comparing TLV and BOC have been performed so far.

Methods

All consecutive individuals who initiated triple HCV therapy with TLV or BOC outside clinical trials at three European clinics were evaluated. Rapid virological response (RVR) was defined as unquantifiable HCV RNA (<25 IU/ml) at week 4 for TLV and at week 8 for BOC (4 weeks after lead-in).

Results

A total of 106 patients were evaluated, 33 treated with BOC and 73 with TLV. Median age, gender, body mass index, baseline HCV RNA, HCV subtype 1a (45% versus 42%) and IL28B-CC alleles (29% versus 23%) did not differ significantly in BOC and TLV groups, respectively. HIV coinfection was more prevalent in patients on TLV than BOC (24% versus 44%). Conversely, more patients on BOC than TLV had previously failed pegylated interferon plus ribavirin (82% versus 64%). RVR was achieved by 82% of patients on TLV versus 59% on BOC (P=0.001). Multivariate logistic regression analysis confirmed that TLV use was the strongest predictor of RVR (OR 3.54 [95% CI 1.23, 10.24]; P=0.02), others being HCV subtype 1b versus 1a (OR 3.26 [95% CI 1.17, 9.09]; P=0.02) and low baseline HCV RNA (OR 0.41 [95% CI 0.16, 1.03]; P=0.06). Prior interferon exposure, HIV coinfection or absence of advanced liver fibrosis did not influence the likelihood of RVR.

Conclusions

Compared to BOC, triple therapy with TLV produces greater RVR rates. TLV might be a better option in more difficult-to-cure patients, such as those with high baseline HCV RNA and/or HCV 1a subtype. HIV coinfection does not influence early HCV RNA responses.

References

Ghany

M.G.

, Nelson

D.R.

, Strader

D.B.

, Thomas

D.L.

, Seeff

L.B.

An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 1433–1444.

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55: 245–264.

Fried

M.W.

, Shiffman

M.L.

, Reddy

K.R.

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975–982.

Jacobson

I.M.

, McHutchison

J.G.

, Dusheiko

Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364: 2405–2416.

Sherman

K.E.

, Flamm

S.L.

, Afdhal

N.H.

Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 2011; 365: 1014–1024.

Poordad

, McCone

, Bacon

Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195–1206.

Zeuzem

, Andreone

, Pol

Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364: 2417–2428.

Bacon

B.R.

, Gordon

S.C.

, Lawitz

Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1207–1217.

Medrano

, Neukam

, Rallón

Modeling the probability of sustained virological response to therapy with pegylated interferon plus ribavirin in patients coinfected with hepatitis C virus and HIV. Clin Infect Dis 2010; 51: 1209–1216.

10.

Berg

, Sarrazin

, Hermann

Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology 2003; 37: 600–609.

11.

Jensen

D.M.

, Morgan

T.R.

, Marcellin

Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon α-2a (40 kd)/ribavirin therapy. Hepatology 2006; 43: 954–960.

12.

Ghany

M.G.

, Strader

D.B.

, Thomas

D.L.

, Seeff

L.B.

Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49: 1335–1374.

13.

Andriulli

, Iacobellis

, Valvano

M.R.

Estimates of HCV-1 patients attaining RVR following dual therapy with peginterferon and ribavirin. Dig Dis Sci 2013; 58: 1371–1382.

14.

Bouchardeau

, Cantaloube

J.F.

, Chevaliez

Improvement of HCV genotype determination with the new version of the INNO-LiPA HCV assay. J Clin Microbiol 2007; 45: 1140–1145.

15.

Ziol

, Handra-Luca

, Kettaneh

Non-invasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005; 41: 48–54.

16.

Castera

Transient elastography and other on invasive tests to assess hepatic fibrosis in patients with viral hepatitis. J Viral Hepat 2009; 16: 300–314.

17.

Kirk

G.D.

, Astemborski

, Mehta

S.H.

Assessment of liver fibrosis by transient elastography in persons with hepatitis C virus infection or HIV-hepatitis C virus coinfection. Clin Infect Dis 2009; 48: 963–972.

18.

Poordad

, Bronowicki

J.P.

, Gordon

Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology 2012; 143: 608–618.

19.

Thompson

A.J.

, Muir

A.J.

, Sulkowski

M.S.

Interleukin-28B polymorphism improves viral kinetics and is the strongest pre-treatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010; 139: 120–129.

20.

Rallón

N.I.

, Soriano

, Naggie

IL28B gene polymorphisms and viral kinetics in HIV/hepatitis C virus-coinfected patients treated with pegylated interferon and ribavirin. AIDS 2011; 25: 1025–1033.

21.

Vispo

, Rallon

N.I.

, Labarga

, Barreiro

, Benito

J.M.

, Soriano

Different impact of IL28B polymorphisms on response to peginterferon-α plus ribavirin in HIV-positive patients infected with HCV subtypes 1a or 1b. J Clin Virol 2012; 55: 58–61.

22.

Rallón

N.I.

, Pineda

J.A.

, Soriano

Differences in virological response to peginterferon-α plus ribavirin in HIV-positive patients coinfected with HCV subtypes 1a or 1b. J Acquir Immune Defic Syndr 2012; 60: 117–123.

23.

Poveda

, Vispo

, Barreiro

Predicted effect of direct acting antivirals in the current HIV-HCV-coinfected population in Spain. Antivir Ther 2012; 17: 571–575.

24.

Grint

, Peters

, Vogel

Temporal changes and regional difference in treatment uptake of hepatitis C therapy in EuroSIDA. J Int AIDS Soc 2012; 15 Suppl 4: 18118.

25.

Blanco

, Barreiro

, Ryan

Risk factors for advanced liver fibrosis in HIV-infected individuals: role of antiretroviral drugs and insulin resistance. J Viral Hepat 2011; 18: 11–16.

26.

Qurishi

, Kreuzberg

, Lüchters

Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet 2003; 362: 1708–1713.

27.

Barreiro

, Vispo

, Labarga

, Soriano

Management and treatment of chronic hepatitis C in HIV patients. Semin Liver Dis 2012; 32: 138–146.

28.

Núñez

, Miralles

, Berdún

M.A.

Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses 2007; 23: 972–982.

29.

Soriano

, Sherman

, Rockstroh

Challenges and opportunities for hepatitis C drug development in HIV-HCV co-infected patients. AIDS 2011; 25: 2197–2208.

30.

Lacombe

, Rockstroh

HIV and viral hepatitis coinfections: advances and challenges. Gut 2012; 61 Suppl 1: i47–i58.

31.

Ingiliz

, Rockstroh

HIV-HCV co-infection facing HCV protease inhibitor licensing: implications for clinicians. Liver Int 2012; 32: 1194–1199.

32.

Naggie

, Sulkowski

Management of patients coinfected with HCV and HIV: a close look at the role for direct-acting antivirals. Gastroenterology 2012; 142: 1324–1334.

33.

Thomas

D.L.

, Bartlett

J.G.

, Peters

M.G.

, Sherman

K.E.

, Sulkowski

M.S.

, Pham

P.A.

Provisional guidance on the use of hepatitis C virus protease inhibitors for treatment of hepatitis C in HIV-infected persons. Clin Infect Dis 2012; 54: 979–983.

34.

Sulkowski

, Sherman

, Soriano

Telaprevir in combination with peginterferon-alfa 2a/ribavirin in HCV-HIV coinfected patients: SVR24 final study results. 63rd American Association for the Study of Liver Diseases. 23–26 November 2012, Boston, MA, USA. Abstract 76.

35.

Mallolas

, Pol

, Rivero

Boceprevir plus peginterferon/ribavirin for the treatment of HCV/HIV co-infected patients: end of treatment (week 48) interim results. 47th European Association for the Study of the Liver. 18-22 April 2012, Barcelona, Spain. Abstract 50.

36.

Bruno

, Mangia

Futility of antiviral treatments for hepatitis C: an evolving concept entering the direct antiviral agents era. Dig Liver Dis 2013; 45: 356–361.

37.

Seden

, Back

, Shoo

New directly acting antivirals for hepatitis C: potential for interaction with antiretrovirals. J Antimicrob Chemother 2010; 65: 1079–1085.