Nonresponse to adefovir: Host or virus dependent?

Abstract

1 d The introduction of adefovir as a drug against lamivuine resistant hepatitis B virus initially raised considerable ope, but reports of subsequent studies have presented conicting results. While recent publications (Zeng et al., 2006; ampertico et al., 2005; Hadziyannis and Papatheodoridis, 006) still confirm a high response rate and no or very litle resistance others report treatment failures in up to 50% as ummarized by Wong and Lok most recently (Wong and Lok, 006). The reasons for these failures appear diverse. Selecion of resistant virus variants with mutations rtA181V/T or tN236T occurs in up to 29% after 5 years (Wong and Lok, 006) or in 31.5% in even shorter periods (Osiowy et al., 006). Probably as important as acquired resistance is priary nonresponse to adefovir. We have recently described n HBV variant, which existed in three nonresponders even efore adefovir treatment. The associated mutation rtI233V equired a 6–10 times higher adefovir concentration for 50% nhibition of replication in vitro than the wild type (Schildgen t al., 2006). This variant occurs in ca. 2% of the patients orldwide (Schildgen et al., 2006; Chang and Lai, 2006). owever, van Bommel et al. reported in the August issue of EPATOLOGY that nonor weak responders to adefovir are uch more frequent (20/127) and they all carried either wild ype virus or lamivudine resistant variants without adefovir esistance markers (van Bommel et al., 2006). In our small ollection of five adefovir treatment failures in HIV negative atients, we observed only one case of infection without the nown adefovir resistance-inducing mutations. A 22-yearld female patient with a HBeAg positive chronic hepatitis B