Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor.
Combination antiretroviral therapy has transformed the prognosis and life expectancy of HIV-1 infected individuals in resource-rich settings. British guidelines currently recommend the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz as part of first-line treatment in therapy-naive HIV-1 infected individuals. However, efavirenz is limited by its low genetic barrier to the development of resistance, together with its potential for CNS toxicities. To overcome these obstacles, several 'next-generation' NNRTIs are in various stages of clinical development. Here, we review the journey of rilpivirine (also known as TMC278, Tibotec), from the discovery of the chemical compound, through successful Phase I and II development, to its current position of being studied in international Phase III trials for the treatment of therapy-naive HIV-1 infected subjects using a 25 mg daily dose. Pharmacokinetic findings and food and drug interactions are discussed, together with safety profile. Rilpivirine has demonstrated high antiviral activity (including against NNRTI-resistant isolates) in vitro, with similar rates of virological suppression in therapy-naive individuals at 96 weeks when compared to efavirenz. Rilpivirine seems to be well tolerated with less CNS disturbance than efavirenz, and has non-teratogenic potential; however, unfavorable interactions with acid suppressant medications will require heightened vigilance when rilpivirine is used in widespread clinical practice.
Garvey
Lucy
L
Clinical Research Fellow, Imperial College London, Division of Medicine, Ground Floor, Clinical Trials, Winston Churchill Wing, London W21PG, London, UK. l.garvey@imperial.ac.uk
Winston
Alan
A
D000818:Animals; D018565:Food-Drug Interactions / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009570:Nitriles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068696:Rilpivirine
D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine