Prevalence of TMC278 (rilpivirine) associated mutations in the Frankfurt Resistance Database.
BACKGROUND
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
Objective of our investigation was to determine the prevalence of mutations E138K, Y181I/V, and K101E/P before the approval of rilpivirine.


METHODS
The Frankfurt Resistance Database consists of 7295 samples which have been sent for resistance testing since 1995.


RESULTS
The E138K, Y181I/V, and the K101E mutations were found in 0.4%, 0.9%, and 2.4% of the patients, respectively.


CONCLUSIONS
Based on these findings we do not expect a broad cross-resistance to rilpivirine due to previous treatment failures of NNRTI-containing regimens.
Institute for Medical Virology, Johann Wolfgang Goethe-University Hospital, Paul-Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany. claudia.reinheimer@kgu.de
Claudia
C
Reinheimer
Hans W
HW
Doerr
Martin
M
Stürmer
D016009:Chi-Square Distribution; D030541:Databases, Genetic; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology*; D015995:Prevalence; D011743:Pyrimidines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068696:Rilpivirine
D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D000068696:Rilpivirine