Assessment of Pharmacokinetic Interactions of the HCV Ns5A Replication Complex Inhibitor Daclatasvir with Antiretroviral Agents: Ritonavir-Boosted Atazanavir, Efavirenz and Tenofovir

Bifano, Marc; Hwang, Carey; Oosterhuis, B.; Hartstra, Jan; Grasela, Dennis M.; Tiessen, Renger G.; Velinova-Donga, Maria; Kandoussi, Hamza; Sevinsky, Heather; Bertz, Richard

doi:10.3851/imp2674

Cited by 82 publications

(77 citation statements)

References 34 publications

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“…), a 90 mg dose of DCV has been recommended. 22 When used with potent CYP3A4 inhibitors (e.g. ritonavir-boosted atazanavir), a 30 mg dose of DCV has been recommended.…”

Section: Daclatasvir (Dcv)mentioning

confidence: 99%

“…On the other hand, DCV dose needs to be increased to 90 mg when it is administered with inducers of CYP3A4 (efavirenz and etravirine). 22 The safety and efficacy of DCV and SOF therapy in HCV and HIV coinfection has been shown in the ALLY-2 trial, which had evaluated a 12-week vs. 8-week regimen in GT-1 to 4 in treatment-naive (n = 151) and treatment-experienced (n = 52) HIV and HCV coinfected patients. The study showed a SVR at 12 weeks (SVR12) of 96% with 12-week combination therapy, but in case of 8-week therapy, the SVR12 was only 76%.…”

Section: Management Of Hcv In Hiv Coinfectionmentioning

confidence: 99%

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Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. ( J CLIN EXP HEPATOL 2016;6:119-145) T here have been revolutionary changes in the management of chronic hepatitis C (CH-C) over the last few years. Pegylated interferon alfa (Peg-IFNa) plus ribavirin (RBV) therapy, which till the recent past was the standard of care, has been eclipsed by the arrival of newer directly acting antiviral agents (DAAs). Not only do the DAAs have better efficacy, they are also associated with lower side effects, have better tolerability, a shorter duration of therapy, and have simpler administration.In the recent guidelines issued by the American Association for the study of Liver Diseases (AASLD), in collaboration with the Infectious Diseases Society of America 1 and the European Association for Study of the Liver z (EASL), 2 the role of Peg-IFNa/RBV therapy in the management of HCV has been relegated to second-line, backup status. These newer guidelines, however, cannot be implemented in India as many of the recommended drugs are yet to be marketed in India. Other considerations for the treatment of HCV in India are a predominance of

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“…), a 90 mg dose of DCV has been recommended. 22 When used with potent CYP3A4 inhibitors (e.g. ritonavir-boosted atazanavir), a 30 mg dose of DCV has been recommended.…”

Section: Daclatasvir (Dcv)mentioning

confidence: 99%

Section: Management Of Hcv In Hiv Coinfectionmentioning

confidence: 99%

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

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“…Ritonavirboosted atazanavir increased DCV AUC by 2.1-fold, whereas efavirenz reduced DCV AUC by 32%. DCV dose modification from 60 mg to 30 mg with ritonavir-boosted atazanavir and 90 mg with efavirenz were predicted to normalize AUC relative to the target exposure [23,24]. No interaction was observed with TDF [24].…”

Section: Daclatasvirmentioning

confidence: 99%

“…DCV dose modification from 60 mg to 30 mg with ritonavir-boosted atazanavir and 90 mg with efavirenz were predicted to normalize AUC relative to the target exposure [23,24]. No interaction was observed with TDF [24]. A DCV dose reduction to 30 mg was assumed to be appropriate for other ritonavir-boosted protease inhibitors given the interaction observed with ritonavir-boosted atazanavir.…”

Section: Daclatasvirmentioning

confidence: 99%

Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV

Miyagami

Kiser

2016

Clin Infect Dis.

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Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission. HIV accelerates the progression of HCV disease; thus, coinfected individuals are at high priority for HCV treatment. Several new HCV therapies, called direct-acting antiviral agents (DAAs), are available that achieve cure rates of >90% in many patient populations including individuals with HIV. The primary consideration in treating HCV in HIVinfected persons is the potential for drug interactions. We describe the clinical pharmacology and drug interaction potential of the DAAs, review the interaction data with DAAs and antiretroviral agents, and identify the knowledge gaps in the pharmacologic aspects of treating HCV in individuals with HIV coinfection. This review will focus on DAAs that have received regulatory approval in the United States and Europe and agents in late stages of clinical development.Keywords. hepatitis C virus; human immunodeficiency virus; coinfection; drug interactions; direct-acting antivirals.Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission [1,2]. HIV accelerates the progression of HCV disease. Individuals with HIV coinfection have higher HCV RNA, a more rapid progression of fibrosis, and an increased frequency of liver decompensation and death [3][4][5][6]. Due to the increased risks associated with HIV coinfection, treatment guidelines consider this patient population a "high priority" for HCV treatment [7,8].There have been significant advances in the treatment of HCV in recent years. Pegylated interferon alfa (PEG) and ribavirin (RBV) were the standard of care for this disease for decades, but several agents that directly target specific steps in the HCV lifecycle (Figure 1) have recently received regulatory approval [9]. The approved direct-acting antiviral agents (DAAs) inhibit 3 specific steps in the HCV lifecycle including the NS3/4A protease enzyme, NS5A protein, and the NS5B polymerase. Inhibition of the NS3 protease prevents the cleavage of the replication complex responsible for formation of viral RNA. The NS5B enzyme is essential for HCV replication as it catalyzes the synthesis of the complementary minus-strand RNA and subsequent genomic plus-strand RNA. There are 2 types of NS5B RNA-dependent RNA polymerase inhibitors: nucleotide and nonnucleoside inhibitors. The nucleotide inhibitors are active site inhibitors, whereas the nonnucleoside inhibitors are allosteric inhibitors. Another target, NS5A, encodes a protein that appears to be essential to the replication machinery of HCV and critical in the assembly of new infectious viral particles. However, the specific functions of this protein have not been established.Relative to PEG plus RBV, DAAs are well tolerated, administered for shorter treatment durations (eg, 8-24 weeks), and ultimately achieve high rates of cure (>90%), otherwise known...

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“…47,48 DCV was recently approved in the United States; DCV has been available in the European Union with guidelines for its use in patients with HIV coinfection. 49 Efficacy data from a phase III trial (ALLY-2, NCT02032888) in coinfected patients show excellent response rates in this population in line with other HCV monoinfected and coinfected data for SOF plus an NS5A inhibitor.…”

Section: Wylesmentioning

confidence: 99%

Regimens for Patients Coinfected with Human Immunodeficiency Virus

Wyles

2015

Clinics in Liver Disease

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Assessment of Pharmacokinetic Interactions of the HCV Ns5A Replication Complex Inhibitor Daclatasvir with Antiretroviral Agents: Ritonavir-Boosted Atazanavir, Efavirenz and Tenofovir

Abstract: The pharmacokinetic data support coadministration of daclatasvir with atazanavir/ritonavir, efavirenz and/or tenofovir. A Phase III study in HIV-HCV coinfection has commenced using the described dose modifications.

Cited by 82 publications

References 34 publications

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV

Regimens for Patients Coinfected with Human Immunodeficiency Virus

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