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Clinical Pharmacokinetics and Pharmacodynamics of Etravirine: An Updated Review

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Abstract

Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of human immunodeficiency virus type 1 infection. It is a potent inhibitor of HIV reverse transcriptase and retains activity against wild-type and most NNRTI-resistant HIV. The pharmacokinetic profile of etravirine and clinical data support twice-daily dosing, although once-daily dosing has been investigated in treatment-naïve and treatment-experienced persons. Despite similar pharmacokinetic and pharmacodynamic results compared with twice-daily dosing, larger studies are needed to fully support once-daily etravirine dosing in treatment-naïve individuals. Etravirine is reserved for use in third- or fourth-line antiretroviral treatment regimens, as recommended, for example, in treatment guidelines by the US Department of Health and Human Services—Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Etravirine exhibits the potential for bi-directional drug–drug interactions with other antiretrovirals and concomitant medications through its interactions with cytochrome P450 (CYP) isozymes: CYP3A4, CYP2C9, and CYP2C19. This review summarizes the pharmacokinetic and pharmacodynamic parameters of etravirine, with particular attention to information on drug–drug interactions and use in special patient populations, including children/adolescents, women, persons with organ dysfunction, and during pregnancy.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-8106, USA

    Joshua P. Havens, Kimberly K. Scarsi & Courtney V. Fletcher

  2. Antiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198-8106, USA

    Joshua P. Havens, Anthony T. Podany, Kimberly K. Scarsi & Courtney V. Fletcher

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  1. Joshua P. Havens
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Correspondence to Joshua P. Havens.

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Funding

The authors acknowledge support from the following grants from the National Institutes of Health: 1K23AI134307 (to Anthony T. Podany), 1R01HD085887-01A1 (to Kimberly K. Scarsi), and RO1 AI124965-04 and UM1AI06701 (to Courtney V. Fletcher).

Conflict of interest

Joshua P. Havens reports receiving grants from Gilead Sciences that are paid directly to the University of Nebraska Medical Center. Anthony T. Podany, Kimberly K. Scarsi and Courtney V. Fletcher report no conflicts of interest that are directly relevant to the content of this review.

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Havens, J.P., Podany, A.T., Scarsi, K.K. et al. Clinical Pharmacokinetics and Pharmacodynamics of Etravirine: An Updated Review. Clin Pharmacokinet 59, 137–154 (2020). https://doi.org/10.1007/s40262-019-00830-9

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