Prevalence of TMC278 (rilpivirine) associated mutations in the Frankfurt Resistance Database.

Analysis of the 3D structure of the HIV-1 reverse transcriptase led to the development of TMC278 (rilpivirine), a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), which proved to be effective against wild-type HIV-1 strains and NNRTI-resistant mutants emerging after failure of NNRTI-containing therapy regimens. Recently, rilpivirine associated mutations (e.g. at positions 138, 181 or 101) have been described in vitro and in vivo; however, some of these mutations have also been observed in the past.Objective of our investigation was to determine the prevalence of mutations E138K, Y181I/V, and K101E/P before the approval of rilpivirine.The Frankfurt Resistance Database consists of 7295 samples which have been sent for resistance testing since 1995.The E138K, Y181I/V, and the K101E mutations were found in 0.4%, 0.9%, and 2.4% of the patients, respectively.Based on these findings we do not expect a broad cross-resistance to rilpivirine due to previous treatment failures of NNRTI-containing regimens.