title: N348I in HIV-1 reverse transcriptase counteracts the synergy between zidovudine and nevirapine.
abstract: The efficacy of regimens that include both zidovudine and nevirapine can be explained by the synergistic interactions between these drugs. N348I in HIV-1 reverse transcriptase confers decreased susceptibility to zidovudine and nevirapine. Here, we demonstrate that N348I reverses the synergistic inhibition of HIV-1 by zidovudine and nevirapine. Also, the efficiency of zidovudine-monophosphate excision in the presence of nevirapine is greater for N348I HIV-1 reverse transcriptase compared with the wild-type enzyme. These data help explain the frequent selection of N348I in regimens that contain zidovudine and nevirapine, and suggest that the selection of N348I should be monitored in resource-limited settings where these drugs are routinely used.
authors: Retroviral Biology and Antivirals Laboratory, Centre for Virology, Burnet Institute, Melbourne, Victoria, Australia.
authors: Soo Huey
authors: SH
authors: Yap
authors: Brian D
authors: BD
authors: Herman
authors: Jessica
authors: J
authors: Radzio
authors: Nicolas
authors: N
authors: Sluis-Cremer
authors: Gilda
authors: G
authors: Tachedjian
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology; D024882:Drug Resistance, Viral; D004357:Drug Synergism; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology*; D012641:Selection, Genetic; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D050505:Mutant Proteins; D015215:Zidovudine; D019829:Nevirapine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase