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.
We assessed the effects of hydroxyurea (HU) at a concentration of 50 microM 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.
Palmer
S
S
Center for AIDS Research at Stanford, Stanford University Medical Center, Stanford, California 94305-5107, USA. palmer@SRI.org
Shafer
R W
RW
Merigan
T C
TC
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D016049:Didanosine / Q000494:pharmacology* / Q000633:toxicity; D004352:Drug Resistance, Microbial; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000633:toxicity; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000068698:Tenofovir; D013936:Thymidine / Q000378:metabolism / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; C053001:adefovir; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine; D016049:Didanosine; D013936:Thymidine; D006918:Hydroxyurea