Cross-Resistance between AZT, ddl and other Antiretroviral Drugs in Primary Isolates of HIV-1

Abstract

Primary isolates of human immunodeficiency virus type 1 (HIV-1) were tested for sensitivity to 3′-azido-3′-deoxythymidine (AZT), 3′-fluoro-3′-deoxythymidine (FLT), 2′,3′-dideoxyinosine (ddl), 2′,3′-dideoxycytidine (ddC), and phosphonoformate (PFA) in peripheral blood mononuclear cells (PBMC). Forty-eight isolates from HIV-1-infected patients treated with AZT for various lengths of time were investigated. More than half of the patients harboured virus resistant to AZT after treatment. There was no correlation between resistance and length of therapy. A significant correlation between resistance to AZT and reduced susceptibility to ddl and ddC was apparent. These results indicate that development of resistance to AZT is common in patients treated with AZT and may be associated with reduced sensitivity to ddl and ddC.