Rilpivirine: a second-generation nonnucleoside reverse transcriptase inhibitor

Abstract

Purpose: The pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, dosage and administration, and place in therapy of rilpivirine are reviewed.

Summary: Rilpivirine is a human immunodeficiency virus type 1 (HIV-1)-specific nonnucleoside reverse transcriptase inhibitor (NNRTI) indicated for use in combination with other antiretroviral agents in adult patients not previously treated with antiretroviral therapy. Rilpivirine is primarily metabolized by the cytochrome P-450 (CYP)3A isoenzyme system. Therefore, providers should be cautious when administering drugs that are inhibitors or inducers of this pathway. Coadministration with CYP 3A inhibitors may lead to increased concentrations of rilpivirine, thereby increasing the risk of adverse effects. Coadministration with inducers of CYP3A isoenzymes or drugs that increase gastric pH may lead to decreased concentrations of rilpivirine, thus promoting virological failure or resistance to rilpivirine. Two Phase III, randomized, double-blind, double-dummy, active-controlled trials compared rilpivirine with efavirenz in HIV-infected adults not previously treated with an antiretroviral. The investigators concluded that rilpivirine, when combined with two nucleoside or nucleotide reverse transcriptase inhibitors, was noninferior to efavirenz for reaching the endpoint of confirmed virological response (HIV-1 RNA level of <50 copies/mL) in adults with HIV infection not previously treated with antiretroviral therapy. The most commonly reported adverse effects included depression, insomnia, headache, and rash. Rilpivirine is administered as a single 25-mg tablet given once daily in combination with other antiretroviral drugs in order to optimize efficacy and reduce resistance.

Conclusion: Rilpivirine is a viable NNRTI for HIV-infected patients who have not previously received antiretroviral therapy.