The next generation: etravirine in the treatment of HIV-1 infection in adults refractory to other antiretrovirals

Abstract

Etravirine is a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) that is approved for the treatment of adult human immunodeficiency virus (HIV)-infected patients with documented or suspected resistance to first-generation NNRTIs. Etravirine has a flexible molecular structure that allows it to retain its activity against mutant HIV strains that exhibit resistance to first-generation agents. It is evident that 3 or more etravirine resistance-associated mutations are typically necessary before clinical resistance to etravirine. Safety and efficacy of etravirine are established in antiretroviral treatment-experienced patients in combination with antiretroviral regimens that contain darunavir/ritonavir. In phase III studies, cutaneous reactions occurred in 19% of treated patients and are the most commonly observed adverse event. The typical manifestation is the development of a maculopapular rash within the first few weeks of etravirine therapy. Resolution commonly occurs within 1-2 weeks on continued therapy. Rare cases of severe skin reactions (,0.1%) have been reported. Etravirine is hepatically metabolized by cytochrome P450 (CYP) 3A4, CYP2C9, and CYP2C19. Drug interactions with some antiretrovirals (eg, unboosted protease inhibitors and fosamprenavir/ ritonavir) and medications for other comorbidities (eg, atorvastatin and clarithromycin) have been reported and may require dosage adjustment for the coadministered drug or selection of alternative therapy in some instances. Administration of etravirine with potent inducers of CYP450 is not recommended due to the potential for subtherapeutic etravirine concentrations. In this article, the pharmacology, efficacy, safety, and tolerability of etravirine in adult treatmentexperienced patients with HIV-1 infection are reviewed. Medical literature was identified by MEDLINE and EMBASE searches (1966 to February 2010) using the search terms "etravirine", "TMC125", and "NNRTI".

Nanoparticle-releasing nanofiber composites for enhanced in vivo vaginal retention

“…Importantly, the difference in observations may be attributed to differences in measuring drug content versus NP content. Rapid burst release of ETR from the NP into the lumen and the propensity of ETR to bind proteins in vaginal fluid (as has been seen in plasma [56,57]) may have contributed to the lower drug content observed in vaginal tissues. To evaluate if ETR burst released before reaching vaginal tissue, we measured the in vitro release from ETR-NP under sink conditions and found that >95% of drug had released within 2 h (Supplementary Fig.…”