Bevirimat - Resistance

Resistance

In vitro studies have shown that presence of a number of single nucleotide polymorphisms in the CA/SP1 cleavage site have resulted in resistance to bevirimat. However, mutations at these sites were not found in phase I and II clinical trials. Instead, mutations in the glutamine-valine-threonine (QVT) motif of the SP1 peptide are also known to cause bevirimat resistance. In addition, V362I mutations have been shown to confer strong resistance to bevirimat, where the S373P and I376V mutations may confer low resistance to bevirimat. A further complication of the use of bevirimat is that, since bevirimat targets the CA/SP1 cleavage site, it could also be used in the treatment of protease inhibitor resistant patients. Except for A364V, mutations in the CA/SP1 cleavage site have showed to result in fitness deficits when combined with protease inhibitor resistance. This proposes that these mutations may develop slowly. It has been shown that protease inhibitor resistance can result in an increase in the occurrence of mutations within the downstream QVT motif.