Tenofovir, adefovir, and zidovudine susceptibilities of primary human immunodeficiency virus type 1 isolates with non-B subtypes or nucleoside resistance.
New antiretroviral drugs with activity against strains of human immunodeficiency virus type 1 (HIV-1) with non-B subtypes and with resistance to current antiretroviral drugs are needed. The activity of two nucleotide analogs, tenofovir and adefovir (PMPA and PMEA, respectively), against non-B subtypes and nucleoside-resistant primary HIV-1 isolates was assessed. Tenofovir and adefovir were fully active against a panel of subtypes A, C, D, E, F, G, and group O primary HIV-1 isolates as compared with their respective activity against subtype B isolates. Moreover, the susceptibility of a panel of 10 primary HIV-1 isolates with >10-fold mean resistance to zidovudine, lamivudine, and abacavir was within 2.2-fold of wild-type tenofovir susceptibility for each isolate. An oral prodrug of tenofovir, tenofovir disoproxil fumarate (DF), is currently in phase III clinical trials for the treatment of HIV-1 infection. These in vitro susceptibility results suggest that tenofovir DF may be active in vivo against HIV-1 with nucleoside resistance as well as against HIV-1 with non-B subtypes.
Palmer
S
S
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702-1201, USA. spalmer@ncifcrf.gov
Margot
N
N
Gilbert
H
H
Shaw
N
N
Buckheit
R
R
Miller
M
M
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068698:Tenofovir; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine