etravirine

Etravirine is an antiretroviral medication used in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. It belongs to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class and is marketed under the brand name Intelence in combination antiretroviral therapy regimens.

Mechanism and class

Etravirine binds to the allosteric NNRTI pocket of HIV-1 reverse transcriptase, inhibiting the enzyme’s activity and thus blocking viral replication. It is considered a second-generation NNRTI designed to retain activity against some HIV-1 strains resistant to first-generation NNRTIs such as efavirenz and nevirapine.

Spectrum and resistance

Etravirine exhibits activity against a range of HIV-1 strains, including many with certain resistance mutations to older NNRTIs. Its use is guided by resistance testing and clinical judgment, as cross-resistance with other NNRTIs can limit effectiveness against some mutant viruses. It is generally used in combination with other antiretrovirals rather than as a standalone therapy.

Administration and pharmacokinetics

Etravirine is taken orally, typically at 200 mg twice daily after meals. It is primarily metabolized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP2C9, and CYP2C19, and is excreted in both urine and feces. Dosing and safety may be influenced by liver function and potential drug interactions with other medicines.

Adverse effects and safety

Common adverse effects include rash, nausea, vomiting, and changes in lipid levels. Hepatic enzyme elevations and hypersensitivity reactions have been reported. As a substrate and modulator of several drug-metabolizing enzymes, etravirine can interact with other medications, necessitating careful evaluation of concomitant therapies.

Clinical use

Etravirine is approved for use in treatment-experienced adults with HIV-1 infection and is considered an option for patients with resistance to first-generation NNRTIs. It is used in combination with other antiretroviral agents as part of a comprehensive HIV treatment regimen.