CORESISTANCE TO ZIDOVUDINE AND FOSCARNET IS ASSOCIATED WITH MULTIPLE MUTATIONS IN THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE

Human immunodeficiency virus type 1 (HIV-1) isolates obtained from a p atient with AIDS were assessed for coresistance to foscarnet and zidov udine. An HIV-1 strain (AP20) coresistant to foscarnet and zidovudine was isolated after 20 months of continuous combination therapy. The re verse transcriptase (RT) gene of AP20 had 41 substitutions which were different from the HXB2-D sequence and 9 that were different from the sequence of its foscarnet-sensitive, zidovudine-resistant progenitor v irus (AP6). Six of these mutations were nonpolymorphic (T39A, V108I, K 166R, K219R, K223Q, and L228R). Both strains had the conventional muta tions mediating zidovudine resistance. In vivo selection may result in HIV-1 strains that are coresistant to foscarnet and zidovudine, but c oresistance appears to require a complex evolutionary path and multipl e RT mutations.