Hydroxyurea enhances the activities of didanosine, 9- [2(phosphonylmethoxy)ethyl]adenine, and 9-[2(phosphonylmethoxy)propyl] adenine against drug-susceptible and drug-resistant human immunodeficiency virus isolates

Abstract

We assessed the effects of hydroxyurea (HU) at a concentration of 50 μM on the in vitro activities of 2',3'-dideoxyinosine (ddI), 9-[2- (phosphonylmethoxy)ethyl]adenine (PMEA), and 9-[2- (phosphonylmethoxy)propyl]adenine (PMPA) against a wild-type human immunodeficiency virus (HIV) type 1 (HIV-1) laboratory isolate and a panel of five well-characterized drug-resistant HIV isolates. Fifty micromolar HU significantly increased the activities of ddI, PMEA, and PMPA against both the wild-type and the drug-resistant HIV-1 isolates. In fixed combinations, both ddI and PMEA were synergistic with HU against wild-type and drug- resistant viruses.