New directly acting antivirals for hepatitis C: potential for interaction with antiretrovirals.

Recent advances in the development of agents that act specifically to inhibit hepatitis C virus (HCV) are set to fundamentally change the way that patients will be treated. New directly acting anti-HCV agents such as protease and polymerase inhibitors will initially be added to standard of care with pegylated interferon-alpha and ribavirin. However, future therapy is likely to constitute combinations of agents which act at distinct stages of viral replication and have differing resistance profiles. While directly acting anti-HCV agents will undoubtedly improve treatment outcomes, the introduction of combination therapy may not be without complications in some patient groups. HIV-positive patients who are receiving antiretrovirals (ARVs) are relatively highly represented among those with HCV infection, and are at high risk of drug-drug interactions (DDIs). As combination anti-HCV treatment gradually evolves to resemble anti-HIV therapy, it is essential to consider the increased potential for DDIs in patients receiving combination anti-HCV therapy, and particularly in HCV/HIV-co-infected individuals. Therapeutic drug monitoring is likely to play a role in the clinical management of such interactions.

[1]  F. Carrat,et al.  Early virologic failure in HIV-coinfected hepatitis C patients treated with the peginterferon-ribavirin combination: does abacavir play a role? , 2007, Journal of acquired immune deficiency syndromes.

[2]  R. Roldán,et al.  Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[3]  William M. Lee,et al.  991 FINAL RESULTS OF THE IDEAL (INDIVIDUALIZED DOSING EFFICACY VERSUS FLAT DOSING TO ASSESS OPTIMAL PEGYLATED INTERFERON THERAPY) PHASE IIIB STUDY , 2008 .

[4]  R. Ptak,et al.  Inhibition of Human Immunodeficiency Virus Type 1 Replication in Human Cells by Debio-025, a Novel Cyclophilin Binding Agent , 2008, Antimicrobial Agents and Chemotherapy.

[5]  P. Kwo,et al.  Boceprevir, an NS3 protease inhibitor of HCV. , 2009, Clinics in liver disease.

[6]  P. Reiss,et al.  Abacavir and cardiovascular risk , 2010, Current opinion in infectious diseases.

[7]  K. Reddy,et al.  Ribavirin: current role in the optimal clinical management of chronic hepatitis C. , 2009, Journal of hepatology.

[8]  J. Macías,et al.  Predictors of Severe Haematological Toxicity Secondary to Pegylated Interferon plus Ribavirin Treatment in HIV-HCV-Coinfected Patients , 2007, Antiviral therapy.

[9]  F. Carrat,et al.  Risk Factors for Symptomatic Mitochondrial Toxicity in HIV/Hepatitis C Virus-Coinfected Patients During Interferon Plus Ribavirin-Based Therapy , 2005, Journal of acquired immune deficiency syndromes.

[10]  V. Soriano,et al.  Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patients. , 2006, Journal of viral hepatitis.

[11]  X. Tong,et al.  P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile. , 2010, Bioorganic & medicinal chemistry letters.

[12]  D. Nelson,et al.  A phase III study of the safety and efficacy of viramidine versus ribavirin in treatment‐naïve patients with chronic hepatitis C: ViSER1 results , 2009, Hepatology.

[13]  Dieter Häussinger,et al.  Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. , 2002, The New England journal of medicine.

[14]  Jean-Michel Pawlotsky,et al.  Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. , 2009, The New England journal of medicine.

[15]  J. Pawlotsky,et al.  HCV Genome and Life Cycle , 2006 .

[16]  R. Crabbé,et al.  An evaluation of the cyclophilin inhibitor Debio 025 and its potential as a treatment for chronic hepatitis C. , 2009, Expert opinion on investigational drugs.

[17]  R. Maserati,et al.  Hyperbilirubinemia during Atazanavir Treatment in 2,404 Patients in the Italian Atazanavir Expanded Access Program and MASTER Cohorts , 2009, Infection.

[18]  M. M. Ramírez,et al.  A propósito de tres casos de hiperlactacidemia/acidosis láctica tras el tratamiento de la hepatitis C con interferón pegilado y ribavirina en pacientes coinfectados por VIH , 2002 .

[19]  C. Tural,et al.  Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone. , 2008, The Journal of antimicrobial chemotherapy.

[20]  J. Pawlotsky,et al.  The hepatitis C virus life cycle as a target for new antiviral therapies. , 2007, Gastroenterology.

[21]  N. Rakov Peginterferon alfa-2a plus ribavirin for chronic hepatitis C. , 2003, The New England journal of medicine.

[22]  D. Harnois Telaprevir with Peginterferon and Ribavirin for Chronic HCV Genotype 1 Infection , 2009 .

[23]  Seng-Lai Tan,et al.  Hepatitis C viruses : genomes and molecular biology , 2006 .

[24]  Felipe García,et al.  Depressive Symptoms after Initiation of Interferon Therapy in Human Immunodeficiency Virus-Infected Patients with Chronic Hepatitis C , 2004, Antiviral therapy.

[25]  V. Soriano,et al.  Increase in serum bilirubin in HIV/hepatitis-C virus-coinfected patients on atazanavir therapy following initiation of pegylated-interferon and ribavirin , 2008, AIDS.

[26]  M McCarthy,et al.  Hepatology , 1999, Rapid Medicine.

[27]  C. Tural,et al.  Randomized trial comparing pegylated interferon α‐2b versus pegylated interferon α‐2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients , 2009, Hepatology.

[28]  Frank Bennett,et al.  Toward second generation hepatitis C virus NS3 serine protease inhibitors: discovery of novel P4 modified analogues with improved potency and pharmacokinetic profile. , 2009, Journal of medicinal chemistry.

[29]  V. Tozzi Pharmacogenetics of antiretrovirals. , 2010, Antiviral research.

[30]  D. Snydman,et al.  Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  M. Pawłowska,et al.  The cyclophilin inhibitor Debio 025 combined with PEG IFNα2a significantly reduces viral load in treatment‐naïve hepatitis C patients , 2009, Hepatology.

[32]  R. Crabbé,et al.  The cyclophilin inhibitor Debio‐025 shows potent anti–hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus , 2008, Hepatology.

[33]  M. Manns,et al.  Gilbert's syndrome and hyperbilirubinemia in protease inhibitor therapy--an extended haplotype of genetic variants increases risk in indinavir treatment. , 2009, Journal of hepatology.

[34]  J. Beijnen,et al.  Evaluation of clinical pharmacist interventions on drug interactions in outpatient pharmaceutical HIV‐care , 2004, Journal of clinical pharmacy and therapeutics.

[35]  J. McHutchison,et al.  Oral resiquimod in chronic HCV infection: safety and efficacy in 2 placebo-controlled, double-blind phase IIa studies. , 2007, Journal of hepatology.

[36]  Kenneth Koury,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[37]  R. Elston,et al.  1046 FIRST-IN-MAN DEMONSTRATION OF POTENT ANTIVIRAL ACTIVITY WITH A NUCLEOSIDE POLYMERASE (R7128) AND PROTEASE (R7227/ITMN-191) INHIBITOR COMBINATION IN HCV: SAFETY, PHARMACOKINETICS, AND VIROLOGIC RESULTS FROM INFORM-1 , 2009 .

[38]  K. Kaita,et al.  Albinterferon alfa‐2b dosed every two or four weeks in interferon‐naïve patients with genotype 1 chronic hepatitis C , 2008, Hepatology.

[39]  E. Negredo,et al.  Disorders of body fat distribution in HIV-1-infected patients. , 2009, AIDS reviews.

[40]  R. Enns,et al.  [127] Phil PROOF OF CONCEPT STUDY OF CELGOSIVIR IN COMBINATION WITH PEGINTERFERON o-2b AND RIBAVIRIN IN CHRONIC HEPATITIS C GENOTYPE-1 NON-RESPONDER PATIENTS , 2007 .

[41]  N. Beeching,et al.  Recognition of risk for clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[42]  P. German,et al.  Pharmacokinetics and Pharmacodynamics of GS‐9350: A Novel Pharmacokinetic Enhancer Without Anti‐HIV Activity , 2010, Clinical pharmacology and therapeutics.

[43]  D. Kempf,et al.  Pharmacokinetic Enhancement of the Hepatitis C Virus Protease Inhibitors VX-950 and SCH 503034 by Co-Dosing with Ritonavir , 2007, Antiviral chemistry & chemotherapy.