Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro

In a phase II study of 6-12 months of adefovir dipivoxil treatment in human immunodeficiency virus (HIV)-infected patients, HIV from 8 of 29 patients developed mutations in reverse transcriptase (RT) potentially attributable to adefovir dipivoxil therapy. Recombinant HIV from pre- and posttreatment plasma samples from these 8 patients showed no change or minor decreases in adefovir susceptibility, consistent with the durable antiviral effect obse rved. Additionally, HIV from 8 patients developed the M184V RT mutation bec ause of concomitant lamivudine use. Recombinant HIV pairs from all 4 patien ts with zidovudine-resistant HIV showed statistically significant increases in adefovir susceptibility of 3- to 4-fold (to near wild type IC50), and H IV pairs from 2 of 4 patients with zidovudine-sensitive HIV showed a 2- to 3-fold increase in susceptibility. In growth kinetics studies, expression o f the M184V RT mutation resulted in attenuated viral growth in peripheral b lood mononuclear cell cultures. These studies suggest that patients possess ing HIV with zidovudine and lamivudine resistance mutations may benefit fro m adefovir dipivoxil therapy.