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A Review of the Experimental NNRTI Rilpivirine

This review of the experimental NNRTI rilpivirine summarizes studies demonstrating that the drug has potent activity against HIV, including against NNRTI-resistant strains of the virus. After 96 weeks of treatment, rates of HIV suppression in treatment-naive patients compared favorably with those of efavirenz (Sustiva). The safety profile of rilpivirine was also favorable, with fewer central nervous system disturbances compared with efavirenz and, thus far, no concerns about its use during pregnancy.

Combination antiretroviral therapy (ART) has dramatically changed the prognosis and life expectancy of HIV patients, especially in wealthy countries. British expert guidelines currently recommend the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva) as part of first-line therapy in treatment-naive individuals.

Efavirenz is limited, however, by its low genetic barrier to the development of drug resistance, as well as by its potential for central nervous system (CNS) toxicities. It is also considered contraindicated in pregnant women due to the risk of birth defects (i.e., it is classified as teratogenic).

In an attempt to overcome these limitations, several "next-generation" NNRTIs are in various stages of clinical development. In a review published in the July 2009 issue of Expert Opinion on Experimental Drugs, the authors describe the development of rilpivirine, starting from the discovery of the chemical compound, through Phase 1 and 2 development, to its current position in international Phase 3 trials for the treatment of ART-naive HIV patients. A 25 mg once-daily dose , is being evaluated.

The review authors discuss pharmacokinetic findings, safety profile, and food and drug interactions. Rilpivirine has shown potent anti-HIV activity in laboratory testing, including against NNRTI-resistant HIV. At 96 weeks, it demonstrated rates of virological suppression in treatment-naive individuals comparable to those of efavirenz.

In conclusion the authors wrote, "Rilpivirine seems to be well tolerated and shows less CNS disturbance than efavirenz, and has non-teratogenic potential.

However, they continued, "unfavorable interactions with acid suppressant medications will require heightened vigilance when rilpivirine is used in widespread clinical practice."

Imperial College London, UK and St. Mary's Hospital, London, UK.

7/10/09

Reference
L Garvey and A Winston. Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor (Abstract). Expert Opinion on Investigational Drugs18(7): 1035-1041. July 2009.