Correlation between viral resistance to zidovudine and resistance at the reverse transcriptase level for a panel of human immunodeficiency virus type1 mutants

Using a large panel of human immunodeficiency virus type 1 site-directed mu tants, we have observed a higher correlation than has previously been demon strated between zidovudine (AZT)-triphosphate resistance data at the revers e transcriptase (RT) level and corresponding viral AZT resistance. This enh anced-resistance effect at the RT level was seen with ATP and to a lesser e xtent with PP, when ATP was added at physiological concentrations. The ATP- dependent mechanism (analogous to pyrophosphorolysis) appears to be dominan t in the mutants bearing the D67N and K70R or 69 insertion mutations, where as the Q151M mutation seems independent of ATP for decreased binding to AZT -triphosphate.