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[摘要]：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 11 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. |
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