rilpivirine

Rilpivirine is an antiretroviral medication in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class used to treat human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretrovirals. It is marketed as the standalone tablet Edurant and as part of fixed-dose regimens such as rilpivirine/emtricitabine/tenofovir disoproxil fumarate (Complera in the United States; Eviplera in the European Union) and rilpivirine/emtricitabine/tenofovir alafenamide (Odefsey).

Mechanism of action: Rilpivirine binds to the HIV-1 reverse transcriptase enzyme in a non-competitive manner, inhibiting viral DNA synthesis and slowing replication. It does not act against HIV-2. Resistance can occur with inadequate viral suppression, and baseline NNRTI resistance can reduce the likelihood of treatment success. Common resistance-associated mutations include K103N and Y181C.

Pharmacokinetics and interactions: Rilpivirine oral bioavailability increases with food. It is mainly metabolized by the liver enzyme CYP3A4 and is a substrate of P-glycoprotein, leading to multiple drug interactions. Drugs that induce CYP3A4 (such as certain anticonvulsants and rifamycins) or raise gastric pH (notably proton pump inhibitors) can decrease rilpivirine levels and reduce efficacy.

Dosing and patient selection: The usual dose is 25 mg once daily with a meal, as part of a fixed-dose regimen with emtricitabine and tenofovir (either TDF or TAF). It is generally not recommended for patients with a baseline HIV-1 RNA above about 100,000 copies/mL or with certain resistance patterns.

Adverse effects and monitoring: Common side effects include headache, depression, insomnia, rash, nausea, and fatigue. Rilpivirine tends to have fewer central nervous system effects than some other NNRTIs, but psychiatric symptoms and rash can occur. Liver disease, co-infections, and significant drug interactions require careful monitoring.