MUTATIONS IN THE POL GENE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN INFECTED PATIENTS RECEIVING DIDANOSINE AND HYDROXYUREA COMBINATION THERAPY

The pattern of mutations in the reverse transcriptase (RT) of human im munodeficiency virus type 1 (HIV-1) strains that confer resistance to didanosine (ddI) was analyzed in 2 groups of patients receiving either ddI monotherapy or ddI plus hydroxyurea (HU) combination therapy. Twe lve patients receiving combination therapy and 8 receiving monotherapy were tested. Combinations of ddI plus HU did not prevent the onset of mutations, which emerged in 50% of the patients in this group compare d with 25% of the ddI monotherapy group. In addition, in 1 patient fro m the combination therapy arm, who had a limited response to the thera py, an unusual pattern of mutations was found: the insertion of 2 amin o acids between residues 69 and 70, a region critical for resistance t o nucleoside analogs. The higher efficacy of the combination of HU and ddI compared with that of ddI monotherapy cannot be attributed to a d elayed or decreased onset of resistance to ddI.