Drug–Drug Interaction Studies Between Hepatitis C Virus Antivirals Sofosbuvir/Velpatasvir and Boosted and Unboosted Human Immunodeficiency Virus Antiretroviral Regimens in Healthy Volunteers

Mogalian, Erik; Stamm, Luisa M.; Osinusi, Anu; Brainard, Diana M.; Shen, Gong; Ling, Kah Hiing John; Mathias, Anita

doi:10.1093/cid/ciy201

Cited by 29 publications

(27 citation statements)

References 12 publications

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“…Coadministration of ledipasvir/sofosbuvir with TDF-containing regimens resulted in higher TFV exposures from EFV/FTC/TDF (AUC 98% higher; C max 79% higher) and FTC/rilpivirine (RPV)/TDF (AUC 40% higher); similar increases in TFV exposure (approximately 40%) were observed with other regimens, including ritonavir-boosted ATV or darunavir (DRV) plus FTC/TDF (Harvoni, 2017b). Coadministration of sofosbuvir/velpatasvir with boosted and unboosted TDF-containing regimens resulted in similar effects on TFV (approximately 40% higher AUC and C max for all regimens except EFV/FTC/TDF; TFV AUC 81% higher) (Mogalian et al, 2015a(Mogalian et al, , 2016a(Mogalian et al, ,c, 2018. The relatively larger changes in TFV seen with EFV/FTC/TDF compared with other regimens are due to comparatively lower TFV exposure when administered as EFV/FTC/TDF, which is recommended to be given on an empty stomach.…”

Section: Nucleoside/nucleotide Reverse Transcriptase Inhibitorsmentioning

confidence: 95%

“…Consistent with EFV-mediated CYP3A induction, lower plasma exposure of simeprevir (AUC 71% lower) was observed after coadministration of EFV single agent (Ouwerkerk-Mahadevan et al, 2012a). A decrease in the velpatasvir AUC (53%) was also observed after coadministration of sofosbuvir/velpatasvir with EFV/FTC/TDF, although no impact of sofosbuvir AUC was observed (Mogalian et al, 2015a). Due to a potential loss of therapeutic effect, coadministration of simeprevir or sofosbuvir/velpatasvir with EFVbased regimens is not recommended (Olysio, 2017).…”

Section: Non-nrtismentioning

confidence: 99%

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The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection

et al. 2018

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Several safe and highly effective direct-acting antiviral (DAA) drugs for chronic hepatitis C virus (HCV) have been developed and greatly increase the number of therapeutic options available to successfully treat HCV infection. However, because treatment regimens contain at least two drugs (e.g., elbasvir and grazoprevir, glecaprevir and pibrentasvir, or sofosbuvir with daclatasvir, simeprevir, ledipasvir, or velpatasvir) and up to five drugs (ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin), the potential for drug-drug interactions (DDIs) becomes an important consideration for HCV-infected individuals with comorbidities that require concomitant medications, such as human immunodeficiency virus/HCV coinfection or immunosuppression after liver transplantation. This review details the pharmacokinetics and DDI potential of approved DAAs for the treatment of HCV infection.

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Section: Nucleoside/nucleotide Reverse Transcriptase Inhibitorsmentioning

confidence: 95%

Section: Non-nrtismentioning

confidence: 99%

The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection

et al. 2018

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“…VEL AUC was reduced 50% with TDF/emtricitabine/efavirenz. SOF/VEL increased tenofovir exposures by 40%-81% [47]. VEL AUC was increased by 2.4 fold with ritonavir-boosted atazanavir, and was also increased 20%-30% in the presence of cobicistat-containing regimens.…”

Section: Simeprevirmentioning

confidence: 91%

“…VEL AUC was increased by 2.4 fold with ritonavir-boosted atazanavir, and was also increased 20%-30% in the presence of cobicistat-containing regimens. When TDF was administered with SOF/VEL, there was a 20%-40% increase in tenofovir AUC [47]. As with LDV, this could be problematic in individuals receiving TDF with other agents that raise tenofovir exposures, but TAF is an alternative to TDF in this scenario.…”

Section: Simeprevirmentioning

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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“…Velpatasvir is metabolized by CYP3A4, CYP2C8, and CYP2B6, and is a substrate of the transporters Pgp, BCRP, OAT1B1 and OAT1B3 on which it exerts mild inhibitory action [23,24]. Thus, velpatasvir is more a candidate victim of cytochrome P450 enzymes rather than a relevant perpetrator of drug-drug interactions.…”

Section: Velpatasvirmentioning

confidence: 99%

Current and future challenges in HCV: insights from an Italian experts panel

et al. 2017

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Drug–Drug Interaction Studies Between Hepatitis C Virus Antivirals Sofosbuvir/Velpatasvir and Boosted and Unboosted Human Immunodeficiency Virus Antiretroviral Regimens in Healthy Volunteers

Abstract: SOF/VEL and ARV regimens including ATV, COBI, DRV, DTG, EVG, FTC, LPV, RAL, RPV, RTV, TAF, or TDF may be coadministered without dose adjustment. Use of SOF/VEL with EFV-containing regimens is not recommended due to an approximate 50% reduction in VEL exposure.

Cited by 29 publications

References 12 publications

The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection

The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection

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

Current and future challenges in HCV: insights from an Italian experts panel

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